Galactia lindenii lectin type-II. Proposal of its potential use in diagnostic tools

Galactia lindenii lectin type-II. 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Proposal of its potential use in diagnostic tools Tania M. Cortázar, Nohora A. Vega, Edgar A. Reyes-Montaño, Manuel A. Ballen-Vanegas, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4406005/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Galactia lindenii lectin type-II (GLL-II) belongs to the group of the legume lectins. The present study investigated the GLL-II staining patterns in histological sections of neoplastic and non-neoplastic thyroid tissues. Besides, hemagglutination assays (HA) using the GLL-II on red blood cells (RBCs) of different glycomic profile were performed, complementing previous results. The differential staining in Papillary Thyroid Cancer (PTC), Invasive Encapsulated Follicular Variant Papillary Thyroid Carcinoma (IEFV-PTC), Hashimoto's thyroiditis (HT), and non-neoplastic thyroid with goiter changes, together with the HA results and along with reviewed glycoprofiles of unhealthy conditions in other organs, allowed us to propose the potential utility of GLL-II in lectin platforms used to discriminate human pathological samples from normal ones. The present study shed light on potential applications of GLL-II in determining alterations of glycosylation patterns in specific cells, tissues, or body fluids, as well as glycotopes biomarkers of healthy or pathological conditions. Galatia lindenii lectin diagnostic tool glycotope biomarker hemagglutination Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Lectins are proteins that possess carbohydrate recognition domains (CRD) through which they interact specifically and reversibly with structures in free carbohydrates or associated with proteins and lipids, and these interactions are fundamental in several biological activities [ 1 , 2 ]. The sequence of sugars and the glycosidic bond configurations contribute significantly to the affinity in the interaction between lectins and multivalent oligosaccharides in cellular glycoconjugates [ 3 – 5 ]. Glycotopes, three-dimensional epitopes represented by carbohydrates, are the minimal structural units confer maximum binding affinity to a specific glycan [ 6 , 7 ]. These sugar epitopes occur at specific sites on glycoconjugates where they can be recognized by lectins or antibodies [ 6 – 14 ]. The glycotope concept has allowed an understanding of the contributions of individual structures in the glycan functions and biosynthetic pathways [ 6 , 7 ]. Plant lectins recognize their glycotopes playing a role in developmental and homeostatic functions; they can also recognize glycotopes in foreign organisms promoting symbiosis with nitrogen-fixing bacteria or engaging in defense mechanisms showing insecticidal, antifungal, or antimicrobial properties [ 1 , 4 ]. Lectins are used for various biomedical and agricultural applications due to their biotechnological potential and the increasingly detailed investigation of the binding specificity of their particular ligands [ 1 , 15 , 16 ]. Global glycosylation patterns are heterogeneous between glycoconjugates, cells, tissues, or body fluids, and at the same time are dependent on physiological conditions which allow the comparison of glycomic profiles in biological samples from patients under pathological and healthy states [ 15 , 17 ]. Current diagnosis platforms that include several plant lectins with different specificities ( e.g ., lectin histochemistry, lectin blotting, lectin microarrays) have become valuable tools allowing the detection of glycosylation alterations and the determination of new glycotope biomarkers of healthy or pathological conditions [ 4 , 15 , 17 – 28 ]. The Galactia lindenii plant is endemic to Colombia and belongs to the Diocleae tribu of the Fabaceae family [ 29 ]. The Diocleae type-I lectins are mainly mannose/glucose (Man/Glc)-specific, while Diocleae type-II lectins show affinity for determined galactosides depending on the lectin [ 30 – 41 ]. In agreement with the above, the G. lindenii seed contains the lectins GLL-I (mannose-specific) [ 31 ]; and GLL-II which recognizes the trisaccharide that represents the histo-blood group H-type-II (Fucα1,2Galβ1,4GlcNAc-R), shows preference for O-glycans in comparison to N-glycans, and its binding activity is inhibited by the monosaccharide N-acetylgalactosamine (GalNAc) [ 30 – 32 ]. The present study selected thyroid tissues from patients diagnosed previously with PTC, IEFV-PTC, HT, or non-neoplastic thyroid with goiter changes for histochemical evaluation using the lectin GLL-II. Besides, HA assays on RBCs of distinct glycomic profile were performed, complementing previous data. The results of all the above, along with a review of the glycoprofiles of other unhealthy conditions, indicate the potential utility of GLL-II as part of the lectin platforms used to discriminate human pathological samples from normal ones. The present work sheds light on the potential applications of GLL-II in diagnostic tools. Materials and methods Materials Galactia lindenii seeds collected in Fúquene, Cundinamarca (Colombia) were botanically identified at the Natural Sciences Institute (vouchers COL 15115 and COL 580116) from Universidad Nacional de Colombia (UNAL). Paraffin-embedded tissue specimens block of tissues from patients diagnosed previously with PTC, IEFV-PTC, HT, or non-neoplastic thyroid with goiter changes, were selected from the UNAL Pathology Department Tissue Bank at the Medicine Faculty. Fresh human and sheep blood samples were obtained from the UNAL Clinical Laboratory and Veterinary Faculty’s Hematology Laboratory. Pharmacia and Bio-Rad equipment was used for ion exchange and affinity chromatographies. Sepharose-4B, DEAE-Sephacel, NaCl, protein standards, Clostridium perfringens α-sialidase, bovine liver β-galactosidase, streptavidin and peroxidase were obtained from Sigma-Aldrich. N-hydroxysuccinimide (NHS) ester of biotin (sulfobiotin-X-NHS) was purchased from Calbiochem. The reagents were all analytical grade. Extraction and Purification of GLL-II The purification of GLL-II was carried out as previously described [ 30 ]. The Sepharose-Lactose (Sepharose-Lac) matrix was prepared by coupling ethanol-washed lactose to divinyl sulphone-activated Sepharose 4B [ 42 ]. Buffer changes and protein concentration were performed by ultrafiltration using a 10 kDa MW cut-off cellulose membrane (Millipore, PLG CO6210; Amicon Bioseparations, USA). Protein content was determined by the bicinchoninic acid (BCA) assay [ 43 ]. GLL-II purification steps were evaluated by SDS-PAGE electrophoresis according to Laemmli [ 44 ], and the hemagglutinating activity in each step of lectin purification was determined. Hemagglutinating activity (HA) The HA was assayed by serial lectin dilutions in phosphate buffer saline (PBS, pH 7.2) on microtiter plates using RBC suspensions [ 45 ]. The erythrocytes exposing the Thomsen-Friedenreich (TF) and Thomsen-nouveau (Tn) glycotopes were prepared from suspensions of human type-A RBCs subjected to enzymatic treatment using α-sialidase, or sequentially α-sialidase and β-galactosidase, respectively, following the methodologies described [ 46 , 47 ]. The minimum agglutinating concentration (MAC) represents the lowest tested concentration in a serial dilution of lectin at which cell agglutination was visible. Tissue specimens A block of 21 formalin-fixed paraffin-embedded tissue specimens from patients diagnosed previously with thyroid disorders were selected from the Tissue Bank. Two observers determined the labeling location and percentage of reactive cells on neoplastic and non-neoplastic thyroid tissues. Labeling intensity was assessed using a semiquantitative scale: slight +, moderate ++, and intense +++ (Supplementary Table S1 ). Lectin histochemistry GLL-II lectin was coupled to biotin following a methodology modified by Wu et al [ 48 ], using two successive additions of sulfobiotin-X-NHS (2:1 w/w, 12 h interval). A streptavidin-peroxidase conjugate (SP) was obtained by coupling 1 mg streptavidin to 5 mg peroxidase as described [ 42 ]. Tissue sections were deparaffinized over 12 h at 60 ˚C, hydrated with xylol, and subjected to differential treatment with ethanol (absolute, 96%, and 70%) for 4 min each. The subsequent steps were performed at room temperature. Tissues were cleared with Triton X-100 at 0.1% in PBS for 30 min. An additional recovery step was then taken in a citrate-phosphate buffer, pH 6, for 20 min followed by three washes with PBS-Tween (0.1%) for 5 min. Endogenous peroxidase was inactivated using 0.3% hydrogen peroxide and 10% methanol solution over 30 min. The slices were washed with PBS-Tween and incubated with 200 µl fetal bovine serum (FBS, 10%) for 30 min. Then, the blocking solution was discarded, and the slices were incubated with 10 µg/mL of biotinylated GLL-II in 10% PBS-FBS over 30 min. Next, the tissues were washed with PBS-Tween, incubated with SP (1:1000) in PBS-FBS over 1 h, and developed with 1% 3,3’-diaminobenzidine (DAB) tetrahydrochloride solution (Dako 3468 kit) in Tris-HCl 50 mM, pH 7.3, and 5 µl of H 2 O 2 at 30% /10 mL of solution. Harris hematoxylin stain was used for contrast. Negative controls were processed simultaneously. Progressive dehydration was done with 70, 90, and 96% ethanol for 4 min each. Finally, the slices were mounted on slides with cytoresin and read. Results and discussion GLL-II purification and coupling to biotin The G. lindenii seed extracts were fractioned on diethylaminoethyl cellulose (DEAE)-Sephacel support equilibrated in PBS (Fig. 1 a). This anion exchange chromatography allows GLL-II to be separated from other proteins including the other lectin present in the seeds. GLL-II is in the DEAE-unretained fraction (DEAE-URF: profile fraction I) considering its basic isoelectric point (pI) ~ 8.3, [ 30 ], while GLL-I (pI: 6.15) is in the DEAE-retained fraction (DEAE-RF: profile fraction II) [ 31 ]. DEAE-URF was fractionated on Sepharose-Lac supports. Figure 1 b presents a Lac-affinity chromatographic profile wherein the GLL-II activity is found in the Sepharose-Lac retained fraction (Sepharose-Lac-RF: profile fraction II) eluted with 0.2 M lactose in PBS. No lectin activity has been detected for Sepharose-Lac-URF. SDS-PAGE for Sepharose-Lac-RF consistently revealed the 24 kDa band as being the principal constituent corresponding to the GLL-II monomer (Fig. 1 c, lanes 4 and 5). A band ~ 50 kDa can sometimes be observed (Fig. 1 c) corresponding to the lectin dimer due to incomplete tetramer dissociation, concurring with previous reports [ 30 , 31 ]. Biotin-conjugated GLL-II agglutinated O-type RBCs at a minimum concentration of 1.4 µg/mL (Table 1 ), indicating the lectin activity was preserved after the coupling process. Using Dot-blot, the biotinylated lectin could still be detected with quantities below 0.2 µg (not shown). In Western blot assays, the biotin-conjugated GLL-II subjected to denaturation and heating showed bands of 24 kDa or 50 kDa (Fig. 1 c, lanes 6 and 7). The biotinylated lectin was used in the histochemical assays. Table 1 Stages of Galactia lindenii lectin II (GLL-II) purification and coupling to biotin Steps Vol (mL) Protein concentration (mg/mL) Total protein (mg) Title MAC (µg/mL) Purification fold Pool of extracts 50 21.6 1080 1:256 84 1 DEAE-URF 50 10.2 510 1:2048 50 1.7 Sepharose-Lac-RF 10 2.5 25 1:2048 1.2 70 Biotinylated GLL-II 1 2.9 2.9 1:2048 1.4 60 MAC: minimum agglutinating concentration on O + RBCs (100 µl of protein solution). URF: unretained fraction, RF: retained fraction. Hemagglutinating activity on erythrocytes of different glycomic profile The HA was evaluated with serial dilutions of pure GLL-II on erythrocytes (Table 2 ), complementing previous results with different human and animal RBCs (Table S2). HA approach allows testing multivalent oligosaccharide ligands in the context of a cellular surface environment [ 49 ] and evaluating broad specificities of the lectins [ 30 , 32 , 33 ] since each RBC type exposes determined predominant glycans [ 9 , 50 – 57 ]. The histo-blood groups and related antigens are non-reducing terminal elements of the oligosaccharide chains in glycolipids and glycoproteins expressed on RBCs, as well as, in epithelial and endothelial cells [ 9 , 50 , 51 , 58 – 63 ]. These terminal carbohydrate structures are particularly relevant in medicine because the change in their expression level alters the cell´s phenotype and can serve as markers of unhealthy states [ 64 – 69 ]. Some human glycotopes are listed in the cluster of differentiation (CD) nomenclature for classifying cell surface antigens [ 70 ]. The predominant glycotopes exposed in the RBCs tested in the present study are described in Table 2 using the textual structural representations proposed by the Consortium for Functional Glycomics (CFG) [ 71 ] and indicating the CD number where applicable. Table 2 Minimum hemagglutinating concentration (MAC) of GLL-II lectin on different erythrocyte types Erythrocyte type MAC (µg/mL) Predominant glycotope Glycotope textual structural nomenclature a CD O * 1.2 H-type-II Fucα1,2Galβ1,4GlcNAc-R CD173 TF 2.1 Thomsen-Friedenreich Galβ1,3GalNAcα1-O-S⁄T CD176 Tn 4.3 Tn GalNAcα1-O-S⁄T CD175 Sheep NA Forssman GalNAcα1,3GalNAcβ-R-Cer / * No difference between Rh + and Rh-. a Proposed by the CFG [ 71 ]. Cer: ceramide. CD: cluster of differentiation [ 70 ]. Fuc: fucose. Gal: galactose. GalNAc: N-acetylgalactosamine. GlcNAc: N-acetylglucosamine. NA: no agglutination. R: N/O-glycan or glycolipid remaining part. S/T: serine/threonine. α/β: glycosidic bond configuration. For the agglutination assays, the pure lectin was used (Sepharose-Lac-RF fraction). The HA results corroborated the GLL-II marked preference for human O type RBCs (MAC: 1.2 µg/mL) among all types of human and non-human RBCs evaluated so far (Tables 2 and S2), which correlates with the predominance of the H-type-II glycotope expression in the human O type erythrocyte glycoconjugates (≈ 2.0 x 10 6 sites/erythrocyte) [ 50 , 51 ]. The higher specificity of GLL-II towards the H-type-II glycotope, compared to other glycoforms, has also been observed previously in Enzyme-Linked Lectinosorbent (ELLSA) and lectin inhibition assays [ 30 , 31 ]. On the other hand, here it was probed the agglutinating activity of GLL-II on TF- and Tn-RBCs, which were agglutinated by GLL-II with the second (2.1 µg/mL) and the third (4.3 µg/mL) minimum MACs, respectively, after that of the O type RBCs (Table 2 ). The last agreed with the interactions between GLL-II with free O-glycoforms exhibiting the TF- or Tn-glycotopes, as observed in Dot-blot (DB) assays [ 32 ]. All in vitro tests together indicate that the GLL-II ligands, in order of interaction, are the H-type-II > TF > Tn glycotopes (Tables 2 and S2). The above results are relevant because those three glycotopes have are unregulated in some unhealthy conditions, as indicated later in the text. We also confirmed the lack of GLL-II activity on sheep RBCs (Table 2 ), whose predominant glycotope is the Forssman antigen [ 9 ]. It is noteworthy that despite GLL-II interacting with RBCs and glycoforms exposing the α-GalNAc monosaccharide (Tn) or the Galβ1,3GalNAcα disaccharide (TF), its interaction with oligosaccharides that present α/β-GalNAc or α/βGal in the terminal position is very weak or absent, as is the case of Forssman, LacDiNAc, Galili, and A/B group oligosaccharides [ 30 , 32 ]. Furthermore, GLL-II does not agglutinate canine, murine, equine or cattle RBCs using concentrations up to 1.4 mg/mL of the lectin [ 30 ]; in those RBCs predominate glycans and gangliosides exposing different types of sialic acids (Neu5Ac; Neu5,9Ac2; or Neu5Gc) [ 9 , 52 – 57 ]. Similarly, GLL-II did not interact with glycoproteins exposing N/O-glycans carrying terminal Neu5Ac [ 32 ]. Potential uses of GLL-II lectin in diagnostic tools Glycosylation is a complex post-translational modification involved in critical biological processes, such as protein folding and stability, cell growth, and cellular interactions [ 72 ]. In humans, an altered protein and lipid glycosylation is a hallmark of cancer [ 73 ]. It can impact all steps in tumor progression and immune evasion due to their effects on cell-cell and cell-extracellular matrix (ECM) interactions, cell growth, apoptosis, and cell death [ 74 – 76 ]. In the diagnosis platforms based on glycosylation changes, the commercial lectins UEA-I from Ulex europaeus seeds and TJA-II from Trichosanthes japonica root tubers, which can recognize the fucosylated trisaccharide H-type-II (Fucα1,2Galβ1,4GlcNAc-R), have usually been included [ 18 – 20 , 22 , 27 , 77 ]. The results obtained so far show that GLL-II presents less tolerance to substitutions on the moieties that make up the trisaccharide, compared to UEA-I and TJA-II; furthermore, although the three lectins share some ligands, each of them also has different additional ligands (Table 3 ). So, we propose the inclusion of GLL-II in the lectin platforms to complement the results that can be obtained with UEA-I and TJA-II as described above. Table 3 Differences between GLL-II and commercial lectins that can recognize the glycotope H-type-II Lectin Predominant ligand(s) Additional ligands Terminal α1,2-Fuc Substitutions Mono-saccharide inhibitor on βGal on GlcNAc GLL-II H-type-II 2'-FL, TF, Tn, Increases interaction Does not tolerate α2,3/6-NeuAc/NeuGc or α1,3-Gal (as in Galili) Does not tolerate α1,3-Fuc (as in Le Y ), β1,3-Gal + α1,4-Fuc (as in Le A ) or α2,6-NeuAc/NeuGc. GalNAc UEA-I H-type-II 2'-FL, sulfated 2'-FL, Le Y Increases interaction Does not tolerate α2,3/6-NeuAc. Tolerates sulfation at C6 Tolerates α1,3-Fuc or 6-O-sulfation. L-Fuc TJA-II H-type III, H-type-IV H-type-II, 2'-FL, Sd Increases interaction Does not tolerate α2,3/6-NeuAc or α1,3-GalNAc. Does not tolerate α1,3/4-Fuc. Tolerates α2,6-NeuAc. GalNAc Data: GLL-II [30, 32 and present work]; UEA-I [ 12 , 13 , 16 , 35 , 78 , 79 ]; TJA-II [ 16 , 80 ]. Galilli antigen (α-gal glycotope): Galα1,3Galβ1,4GlcNAc-R. Glc: glucose. Le A : Lewis A antigen, Galβ1,3(Fucα1,4)GlcNAcβ-R.. Le Y : Lewis Y antigen, Fucα1,2Galβ1,4(Fucα1,3)GlcNAc-R. Neu5Gc: N-glycolylneuraminic acid. Sd antigen: GalNAcβl,4Galβl-R. 2'-FL: 2’fucosyllactose, Fucα1,2Galβ1,4Glc-R. Sulfonated forms of 2'-FL: Fucα1,2Galβ1,4(SO 3− α6)O-Glc-R and Fucα1,2(SO 3 )Galβ1,4Glc-R. Other nomenclature and glycosidic bond configurations as in Table 2 . The UEA-I lectin recognizes structures with exposed terminal fucose (Fuc); its predominant ligand is the H-type-II glycotope (Ka: 4,3 x 10 4 M − 1 ; Kd: 8.1 µM, Isothermal Titration Calorimetry, ITC), and it also interacts with the 2'-fucosyllactose (2’-FL; Kd: 12.5 µM, ITC), Lewis Y antigen [Le Y (CD174); Kd: 19.8 µM; ITC], and sulfonated 2’-FL forms. UEA-I interactions are mainly centered on the fucose residues of its ligands (α1,2-Fuc or α1,3-Fuc), whereas it is less sensitive to substitutions in galactose (Gal) and N-acetylglucosamine (GlcNAc) [ 13 , 16 , 35 , 78 , 79 ]. For its part, the TJA-II lectin preferably recognizes oligosaccharides exposing the H-type-III and H-type-IV glycotopes (Fucα1,2Galβ1,3GalNacα/β), which present terminal α1,2-Fuc followed by Gal and GlcNAc linked in a β1,3 bond, as is the case of the Lacto-N-Fucopentose-I (LNFP-I, Ka: 3,05 x 10 5 M − 1 , equilibrium dialysis), whereas for this lectin the H-type-II is an additional ligand [ 16 , 80 ]. Last, according to our in vitro results carried out so far, the GLL-II lectin predominant ligand is the H-type-II glycotope; the interactions with the three moieties within the trisaccharide are relevant since the absence of α1,2-Fuc or GlcNAc, as well as substitutions in β-Gal or GlcNAc avoid the recognition (Tables 2 and 3 ). GLL-II prefers oligosaccharides with terminal α1,2-Fuc followed by Gal and GlcNAc linked in a β1,4 bond. It also interacts with the 2-FL (Ka: 1 x 10 5 M − 1 , Kd: 9,7 µM, by Frontal Affinity Chromatography, FAC; Vega et al , unpublished), and among the non-fucosylated oligosaccharides, its additional ligands are the TF and Tn glycotopes (Tables 2 and S2). GLL-II and TJA-II do not interact with the difucosylated Le Y antigen (α1,2/3-Fuc) [ 30 , 80 ]. The differences on the fine sugar-binding specificity of the three H-type-II-recognizing lectins will depend on the structure, shape, and size of the carbohydrate-binding sites on the lectin CRD, leading to a great diversity in their sugar-recognition capacity. Histochemical evaluation of thyroid disorders using the GLL-II lectin Thyroid cancer is a common endocrine-related malignant tumor with a global increased incidence in recent years [ 81 , 82 ]. The 5th edition of the WHO classification of endocrine tumors released in 2022 integrates the tumor morphological characteristics and the oncogene-driven signaling pathways that have an impact on the intracellular metabolism ( BRAF -like or RAS -like) [ 83 , 84 ], thus categorizing the follicular-derived thyroid tumors into three groups: 1) Benign tumors represented by follicular nodular disease, follicular adenoma, follicular adenoma with papillary architecture, and oncocytic adenoma; 2) Low risk-neoplasms including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), hyalinizing trabecular tumors, and well-differentiated tumor of uncertain malignant potential (WDT-UMP); and 3) Malignant neoplasms which include papillary thyroid (PTC), follicular thyroid (FTC), oncocytic thyroid (OCA), invasive encapsulated follicular variant papillary thyroid (IEFV-PTC), poorly differentiated thyroid (PDTC), differentiated high-grade thyroid (DHGTC), and anaplastic thyroid (ATC) carcinomas [ 83 ]. Glycosylation is altered in thyroid cancer showing differences in expression level of glycoforms when compared to healthy controls, and in turn, between the distinct TC tumor types [ 76 , 85 – 90 ]. Those changes have been seen mainly in fucosylation, sialylation, O-GlcNAcylation, O-GalNAc extension grade [ 90 – 92 ], and glycoconjugate complexity [ 85 , 87 ]. Research in glycobiology and endocrinology point out that oligosaccharides are critically involved in the thyroid functioning and that changes in glycosylation profiles lead to thyroid pathologies, including thyroid carcinogenesis and autoimmunity [ 90 ]. In the present study, tissues from patients diagnosed previously with PTC, IEFV-PTC, HT, or non-neoplastic thyroid with goiter changes, were selected for histochemical evaluation using the biotinylated GLL-II on the different thyroid tissue samples (Figs. 2 – 6 ). A summary of all the evaluated cases, in normal and tumor tissues, is presented in the Table S1 . In normal tissue a non-uniform cytoplasmic granular staining was observed in thyroid follicular cells and colloid (Fig. 3 a), in contrast to samples of distinct thyroid disorders which showed additional or different label intensity and/or distribution (Figs. 2 – 6 ) indicating a site-specific presence of GLL-II ligands in different states of the thyroid gland as described below. Papillary thyroid carcinoma (PTC) PTC is the most frequent form of thyroid cancer. It occurs predominantly in middle-aged adults with a 3:1 female-to-male ratio, and the known risk factors for PTC include exposure to significant ionizing radiation, high dietary iodine, obesity, and genetic syndromes [ 93 ]. In PTC tissues, the GLL-II labeling showed an intense follicular cell apical surface staining together with a moderate cytoplasmic granular label in between 40% and 100% of the cells (Figs. 2 and 3 , Table S1 ), while non-neoplastic tissue presented cytoplasmic non-uniform and granular staining in follicular cells and colloid without evident particular membrane label (Fig. 3 a). The marked GLL-II membrane pattern indicates that the apical surface of PTC follicular cells contains a high amount of receptors for the lectin, and coincides with previous observations where using lectins, monoclonal antibodies (mAbs), and glycosidases, it has been detected a significantly increased expression of fucosylated glycotopes, including the H-type-II [ 77 , 85 , 95 – 101 ], as well as the O-glycan TF [ 77 , 91 , 98 , 102 – 104 ] in human PTC. Additionally, in the same samples (Figs. 2 and 3 ), Harris hematoxylin allowed observing the typical appearance of the enlarged, elongated and overlapping nuclei presenting irregular contours, few mitotic figures, and a pale aspect due to finely textured, evenly distributed chromatin in PTC [ 93 , 94 ]. H-type-II glycotope Fucosylation is altered in inflamed and cancer tissues [ 75 , 76 , 90 ]. Glycoconjugates containing α-Fuc participate in diverse interactions between cells and ECM [ 105 – 107 ], and the change in their expression correlates with tumor growth, invasion, and metastasis [ 95 , 107 – 113 ]. The aberrant fucosylation is mainly attributed to upregulation of fucosyltransferases (FUTs) and downregulation of α-L-fucosidases (FUCAs), promoting inflammatory conditions and malignancy [ 19 – 21 , 105 , 108 , 113 – 115 ]. In particular, the increase of the fucosylated H-type-II glycotope is related to the overexpression of FUT1 and FUT2 that catalyze the transfer of Fuc through an α1,2 link to a terminal Gal in O/N-glycans or lipids [ 20 , 21 , 116 ], leading to the increase of α1,2-fucosylated glycans during the tumor progression in a variety of tissues [ 19 – 21 , 23 – 26 , 100 , 110 , 114 , 116 , 117 ]. Upregulated FUT1 promotes cancer cell proliferation [ 107 , 118 ], and the increase in both FUT1 and FUT2 induces a decrease in cadherin expression, leading to a reduced cellular adhesiveness, a defining feature of cancer [ 116 , 119 ]. The glycoprotein that represents the prostate antigen/kallikrein 3 (PSA/KLK3), the fucosylated GM1 ganglioside (FucGM1) in lung SCC carcinoma [ 19 – 21 ], and the globo-H glycosphingolipid in breast cancer [ 116 ], are α1,2-fucosylated. In they turn, the PTC carcinoma glycoconjugates decorated with α1,2-Fuc in their non-reducing termini carry the following glycotopes: a) H-type-II determined by using GLL-II (Figs. 2 and 3 ), UEA-I [ 77 ], and mAbs [ 95 , 98 , 101 , 120 ], b) Le Y recognized by UEA-I and mAbs [ 77 , 95 , 98 , 101 ], c) Le B detected with mAbs [ 98 , 101 ] (this Lewis antigen contains α1,2-Fuc and also α1,4-Fuc), and d) Globo-H ceramide recognized in tissue microarrays [ 123 ]. In thyroid cancer, the H-type-II glycotope has been more readily and frequently detected in PTC compared to follicular adenomas, FTC and ATC [ 77 , 95 , 97 , 98 , 101 , 120 , 121 ]; meanwhile, it also has been found in the non-acid glycosphingolipid fraction isolated from human neuroendocrine medullary thyroid carcinoma (MTC), as determined by mass spectrometry [ 112 ]. Neoexpression of poly-N-acetyllactosamine structures (poly-LacNAc) is another motif related to the presence of the H-type-II in PTC since poly-LacNAc are direct precursors of that glycotope in cancer cells [ 96 ]. Short and long linear unbranched-, and highly branched poly-LacNAc sequences, have been detected in PTC, while lectins specific to the distinct types of poly-LacNAc exhibited slight or no reactivity with the cells in follicular adenomas and FTC [ 96 , 97 , 124 ]. Last, although normal adult thyroid follicular cells do not express the ABH histo-blood antigens [ 95 – 97 , 120 , 125 ], and the clinical and pathological features did not differ according the ABH blood group of the PTC patient [ 126 ], the reappearance of the H-type-II glycotope had shown a correlation with a loss of A or B antigens during metastases due probably to the lack of A- and B-glycosyltransferase activities [ 95 , 101 ]. Other types of fucosylation also are increased in PTC compared to normal thyroid. That is how the α1,6-Fuc core (FUT8) is a factor related with PTC tumor size and lymph node metastasis [ 99 ]. Furthermore, in addition to Le Y and Le B , the PTC carcinomas also show stronger immunoreactivity to other fucosylated or sialofucosylated forms of Lewis antigens (Le A , Le X , sLe A and sLe X ) [ 64 , 96 – 101 , 120 , 121 ], which carry α1,3-Fuc or α1,4-Fuc added on GlcNAc by FUT3-FUT7 or FUT9 [ 127 ]. The ectopic expression of sLe A and sLe X (normally expressed by leukocytes) by several cancers is associated with malignancy [ 113 ]. The number of Lewis positive cases has been higher in PTC than in FTC carcinomas [ 98 , 120 , 121 ]. However, the α1,3-fucosylation (FUT7) of sialylated glycans in the EGFR receptor promotes tumor-cell proliferation and migration in FTC [ 128 ]. In other ways, the downregulation of FUCAs involved in the hydrolysis of terminal Fuc residues linked via α1,2/3/4/6 bounds to oligosaccharide chains has also been related to increased aggressiveness in thyroid cancer [ 99 , 105 ]. TF glycotope The Thomsen-Friedenreich glycotope is exposed during tumorigenesis due to the defect of glycosyltransferases and chaperones involved in the elongation of the O-glycans [ 129 ]. The interactions mediated by its overexpression play an important role in thyroid, colon, prostate, and bone cancers [ 91 , 102 , 130 , 131 ], including tumor cell attachment to vascular endothelial cells (ECs), invasion and migration [ 102 , 132 – 135 ]. The TF antigen is overexpressed in the membrane and cytoplasm of different cells of PTC tissues in comparison to human normal thyroid [ 77 , 91 , 98 , 102 – 104 ]. In adult normal tissues, the TF glycotope is masked by sialic acid (sTF) [ 91 , 102 , 130 , 136 – 140 ]. The GLL-II can react with the TF present in the PTC tissues, but not with the sTF form in normal thyroid, as the lectin does not interact with sialylated glycotopes [ 30 , 32 ]. Mucin-1 (MUC1) is a common carrier of TF in PTC, and mucin altered glycosylation reduces the interaction with E-selectin, leading to greater invasive and metastatic capacities. MUC1-TF is overexpressed at the apical and lateral membranes in PTC cancer cells [ 91 ], sites that coincide with the intense GLL-II staining in PTC follicular cell membrane (Figs. 2 c and 3 d), in contrast to the diffuse cytoplasmic binding pattern predominant in FTC when TF-specific lectins have been used [ 77 , 104 ]. The high expression of α1,2-fucosylated glycotopes (H-type-II, Le Y , Le B , globo-H glycosphingolipid) and TF antigen shows the potential utility of these glycan structures as biomarkers for PTC tissues. Multivariate analyses have indicated a strong association between the globo-H and MUC1-TF expressions with the presence of the BRAF-phenotype and lymph node metastasis [ 123 , 141 ]. Since those glycotopes are exposed in a greater proportion in PTC cell membranes than in FTC, it could be hypothesized that they play a role in promote the first steps of the BRAF-transcriptomic profile observed in PTC [ 83 , 84 ]. At the same time, the typical RAS-signaling in FTC would depend on other types of glycotopes. Future research into the relationship between the type of membrane glycoconjugates and transcriptomics could support the distinction between the different TC types in more detail. Invasive encapsulated follicular variant papillary thyroid carcinoma (IEFV-PTC) In IEFV-PTC tissues, intense and moderate GLL-II staining was present in the Golgi complex (Fig. 4 ). That organelle´s unique and specific label has not been described before in thyroid cancer. This result could be related to failures in transporting newly synthesized glycoconjugates (containing GLL-II ligands) from Golgi to other cellular areas in thyroid cells of IEFV-PTC patients. Malfunctioned Golgi apparatus plays pivotal roles in multiple human cancers [ 142 – 146 ]. In the secretory pathway, once exported from the endoplasmic reticulum (ER) and reaching the trans -side of the Golgi, newly synthesized cargos are packed into membrane carries destined for specific sites of cells i.e ., cell membrane or endolysosomes, or secreted outside [ 146 – 149 ]. Recently, it was uncovered that the glycans could function as a generic Golgi export signal at the trans -Golgi for constitutive exocytic trafficking; this mechanism can be alternative or complementary to the conventional amino acid short stretch signals that are recognized by diverse trafficking machineries [ 92 ]. By using superresolution microscopy, Golgi disassemblers and blockers of the O-GalNAc extension, it was observed that secretory cargos displayed substantial Golgi localization when their O-glycosylation is truncated, compared with the extended O - glycans, which promote the Golgi export [ 92 ]. In that scenery, the Golgi specific GLL-II staining in IEFV-PTC carcinoma (Fig. 4 ) could be due to higher expression of truncated O-glycans ( eg ., Tn glycotope) in the Golgi trapped glycoproteins. Then, poor functioning/low expression level of glycosyltransferases that extend the O-glycosylation and/or failures in the protein transport system ( eg ., glycan receptors, enzymes; free or in vesicles) would be characteristics in IEFV-PTC. Current and future research in Golgi functioning and glycosylation [ 143 ] could show more refined differences between the footprints in the tissues of the distinct thyroid tumor types, including IEFV-PTC. Non-neoplastic thyroid with goiter changes In non-neoplastic thyroid with goiter changes, the GLL-II showed blood vessel staining, cytoplasmic granular label in follicular and C-cells, and non-uniform in colloid (Fig. 5 ). While adult normal thyroid epithelial cells are H-type-II deficient [ 95 , 97 , 120 , 125 ], the vascular ECs do express that glycotope [ 60 , 77 , 95 , 101 , 150 ]. It has been reported that the α1,2-fucosylated trisaccharide can participate in cell adhesion on endothelia through its interaction with some galectins [ 150 ]. On the other hand, the TF antigen is also present in ECs, and it is critical for the vascular integrity [ 151 ]. Both GLL-II (Fig. 4 , Table S1 ) as well as UEA-I [ 77 ] mark the vascular ECs as these structures contain receptors carrying exposed ligands for the two lectins [ 101 , 135 , 150 ], i.e ., H-type-II (shared ligand), Le Y (UEA-I), TF (GLL-II), and Tn (GLL-II) glycotopes. The label of vascular endothelia using GLL-II or UEA-I is independent of the patient´s ABH blood type, so both lectins could be useful to demonstrate small vessel invasion. On the other hand, the moderate C-cell labeling with GLL-II coincides with the pattern previously observed in those cells using H-type-II-specific lectins in neoplastic and non-neoplastic thyroid tissues [ 77 ]. In some thyroid goiter samples it was observed moderate irregular colloid staining with GLL-II (Fig. 5 c). The colloid is composed mainly of the highly glycosylated prohormone thyroglobulin (Tg), which carryies N-glycans containing high mannose, sialylated, α1,6-fucosylated, bisecting, and LacNAc glycotopes [ 152 ]. A single chondroitin sulfate unit is linked to the residue Ser2730 [ 153 ], however, the precise structure of other O-glycans on Tg is still unknown [ 90 ]. None of the Tg glycotope structures reported above represents a GLL-II ligand. Meanwhile, colloid is TF-deficient [ 91 ]; and colloid in benign goiter has showed weak positive reaction to Forssman-specific lectins [ 77 ]. The moderate staining with GLL-II (Fig. 5 c) and UEA-I [ 77 ] evidences a probable increase in the H-type-II glycotope in non-neoplastic thyroid with goiter changes, which could be verified in the future using other platforms. Hashimoto’s thyroiditis (HT) The common autoimmune thyroid disorder HT is characterized by marked lymphocyte and plasma cell infiltration of the parenchyma and antibodies specific to thyroid antigens [ 28 , 154 – 156 ]. The thyroid structure can be destroyed by activated T-lymphocytes inducing chronic inflammation and the late-stage disease can resemble the histology of lymphatic tissue [ 156 , 157 ]. Inflammatory infiltrates in tumor tissue may represent a condition preceding the development of malignancy, and that is how HT can be frequently observed in PTC, and immune dysregulation is involved in both disorders [ 158 ]. In the HT tissues, the GLL-II staining was observed in the germinal center of the lymphoid follicles and, in some cases, in the apical and granular cytoplasmic portions of the follicular cells (Fig. 6 ). The GLL-II label of lymphoid follicles is in agreement with the presence of the H-type-II and TF glycotopes, which in conjunction with sialofucosylated glycotopes (sLe X , sLe A , and 6-sulfo sLe X ) and hyaluronic acid, regulate the adhesion/rolling of leukocytes migrating to the inflammation sites, interacting with carbohydrate binding proteins as galectin-9, galectin-3, selectins and CD44, respectively [ 67 , 135 , 150 , 151 ]. Thyroid biological sample source and glycosylation Glycosylation differs in pathological when compared to healthy conditions, and in turn some features also depend on the source of the biological sample, i.e ., tissues or fluids. Using sialic acid-binding lectins, mAb, and MALDI-TOF approaches, it was found upregulation of α2,6-sialylated glycans in both thyroid tissue and plasma of PTC patients [ 85 – 87 , 98 , 159 , 160 ]; as well as downregulation of high-mannose type N - glycans was found in both types of PTC samples [ 85 , 87 – 89 ]. On the other hand, fucosylation and complex type N - glycans increase in PTC tissues [ 85 ] while both decrease in plasma and serum N-glycome of PTC patients [ 87 , 88 ] when compared with the respective healthy controls. Increased levels of terminal mono- and disaccharide α/β-GalNAc glycotopes are present in HT patient´s thyroid tissue and blood [ 16 , 28 , 77 ]. However, unlike HT tissues, low levels of α1,2-Fuc have been detected in the glycan antennas of HT peripheral blood mononuclear cells (PBMCs) [ 90 ], and high levels of sialylated glycans are present in the sera of HT patients with advanced thyroid destruction [ 157 ]. The increase in serum glycoconjugate sialylation is related to the presence of the β-galactoside α2,6-sialyltransferase 1 (ST6Gal1), which is active in the bloodstream of the HT patients, independently from the classical pathway of cellular glycosylation in ER and Golgi [ 157 , 161 ]. In this regard, it has been pointed out that the process of IgG sialylation may explain the great dynamics of inflammatory processes mediated by antibodies in HT [ 161 ]. Potential uses of GLL-II lectin in diagnostic of other conditions Determination of the H-type-II glycotope as the predominant ligand of GLL-II allows us to propose this lectin as part of lectin-based diagnostic platforms that permit differentiating samples where the glycotope expression levels differ between healthy and pathological states. In addition to the patterns observed in neoplastic and non-neoplastic thyroid tissues (Figs. 2 – 6 ), in the consulted bibliography, we found other cases that show differences in the expression of the H-type-II glycotope in different conditions. For example, the H-type-II glycotope is among the overexpressed motifs in serum samples from patients with squamous cell carcinoma (SCC) of non-small cell lung cancer (NSCLC) [ 19 , 21 ] or prostate cancer [ 20 , 22 ], and in biopsies from patients with gastric cancer [ 23 – 26 ] or Helicobacter pylori -infected [ 18 , 26 ]; compared to the healthy conditions or other pathologies in the same organs (Table 4 ). Table 4 Potential uses of GLL-II lectin in the diagnosis of human organism conditions Condition Sample Changes in glycosylation patterns Potential GLL-II appication Expected results using GLL-II Overexpression in pathological Condition High expression in healthy/different condition PTC Thyroid biopsy H-type-II, Globo-H, Le Y , α1,6-Fuc; TF, LacdiNAc, Forssman, terminal GlcNAcα/β, poly-IIβ, Siaα2,6-Tn; Siaα2,3-Le X Siaα2,3-IIβ and oligomannosides. Differentiate between PTC and healthy control. High signal intensity in FC apical membrane and cytoplasm in tissue of PTC patients SCC- NSCLC pulmonary cancer Serum H-type-II; α1,2/6-Fuc; Siaα2,3-TF, LacDiNAc; 3/6-O-sulfated-TF; GlcNAcβ1,4/6Man; Group A; Group B; terminal Man Siaα2,6-Iβ/IIβ; α1,3-Fuc (Le X /Le Y ), poly-IIβ Differentiate between SCC carcinoma and healthy control. High signal intensity in serum from patients with SCC carcinoma in NSCLC. Prostate cancer Serum H-types-II/III/IV; α1,2/6-Fuc; LacDiNAc; Poly-IIβ; α/β-GalNAc; Siaα2,3-IIβ/Le X /TF; 3/6-O-sulfated-IIβ; GlcNAcβ1,4Man Siaα2,6-IIβ Differentiate between prostate cancer and benign prostatic hyperplasia High signal intensity in serum from patients with prostate cancer. Gastric cancer Gastric biopsy H-type-II; α1,2/6-Fuc; α/β-Gal/GalNAc; Siaα2,3-TF/Le A /Le X ; GlcNAcβ1,4/6Man; Siaα2,6-LacDiNAc Multi/poly-IIβ on branched N-glycans in gastric ulcer Discriminate gastric cancer from gastric ulcer High signal intensity in gastric tissues from patients with gastric cancer. H. pylori infection Gastric body biopsy H-type-II; Le X /Le Y ; Siaα2,6Gal/GalNAc. GlcNAcβ1,2/4-Man; terminal α1,3/6-Man; IIβ Discriminate infected from uninfected patient High signal intensity in gastric mucosa of infected patient. Aquilles tendon rupture EV derived from bone marrow MSC Lower level of Fucα1,2 in non-regenerative EV. α1,2-fucosylated glycoconjugates in regenerative EV Establish an isolation system of regenerative EVs High signal intensity in EV with Aquilles tendon regenerative potential Blood typing Human RBCs / ABO groups Recognize O-type RBC Specific O-type RBC agglutination EV: extracellular vesicles. FC: follicular cells. Iβ: LacNAc-I. IIβ: LacNAc-II. Le: Lewis antigens A, Y or X. MSC: mesenchymal stem cells. SCC: squamous cell carcinoma. Sia: sialic acid. Data: Aquilles tendon rupture [ 27 ]; Blood typing [Tables 2 and S2], Gastric cancer [ 23 – 26 ]; H. pylori infection [ 18 , 26 ]; NSCLC: non-small cell lung cancer [ 19 ]; PTC: Papillary Thyroid Carcinoma [77, 85–87, 90, 98, 103, 104, 112, 124, and present work]; Prostate cancer [ 20 , 22 ]. The predominant ligands of the lectins used in the different studies have been updated as described in [ 16 ]. By associating the differences and similarities between the H-type-II-recognizing lectins and the glycosylation changes reported in different states of the organism (Tables 3 and 4 ), some considerations regarding to the glycotopes overexpressed under the opposite physiological conditions should be considered. For example, in the discrimination of patients with pulmonary SCC carcinoma, H-type-II glycotope levels are overexpressed in serum in the pathological condition, while those of the antigen Le Y are high in healthy sera [ 19 ]. For this reason, it is relevant that in platforms for the diagnosis of that type of cancer, along with the UEA-I lectin (which recognizes both H-type-II and Le Y ), another H-type-II-specific lectin that does not recognize Le Y ( e.g ., GLL-II), should also be included. Conversely, UEA-I could be very valuable in diagnosing of H. pylori infection where overexpression of both glycotopes occurs in the infected gastric body [ 18 , 26 ]. On the other hand, as terminal α1,2-Fuc is a biomarker of those extracellular vesicles (EV) derived from bone marrow mesenchymal stem cells (MSC) that have the potential to promote regeneration of Achilles tendon that has experienced rupture [ 27 ], then GLL-II, UEA-I and TJA-II could be tested as the basis of an isolation system for regenerative EVs; as well as, the three lectins may be useful in the diagnosis of prostate cancer due the overexpression of the H-type-II (GLL-II and UEA-I), and H-type-III/IV (TJA-II) glycotopes in the patient sera [ 20 , 22 ]. As described in previous sections, GLL-II and UEA-I are useful lectins in the discrimination between normal thyroid tissue and some thyroid alterations due the overexpression of GLL-II and UEA-I ligands depending on thyroid disorder. Conclusions The GLL-II lectin has high useful potential in diagnostic platforms due its ligands (H-type-II, TF, and Tn glycotopes) are unregulated in unhealthy conditions, allowing to distinguish between healthy and pathological states samples. Due to its high specificity towards the H-type-II glycotope, GLL-II shows great potential as a tool in the detection of this overexpressed biomarker in PTC, gastric cancer, and H. pylori-infected biopsies, as well as in serum of patients of SCC-NSCLC and prostate cancer. Besides, the existing evidence of the presence of the TF structure in PTC, as well as of Tn antigen in gastric cancer biopsies and in the serum of prostate cancer patients, represents an additive advantage when using GLL-II for diagnosing those conditions. Additionally, GLL-II could be tested as the basis of an isolation system for regenerative EVs. For the above, we consider the inclusion of GLL-II in lectin-based diagnostic platforms plausible, taking advantage of the progress in the study of its specificity. Declarations Acknowledgements We thank Dr. Fernández J.L. (from the Universidad Nacional Institute of Natural Sciences) for plant species identification. Financial support was provided by the Universidad Nacional Chemistry Department; and by the Ministry of Science, Technology and Innovation of Colombia (MinCiencias) with the Lamiaceae Lectin Structure project grant 110148925106 and the doctoral student grant 617 - 0656 (T.M.C). Conflict of interest The authors declare that they have no conflicts of interest. Author contributions Study conception, design, material preparation, data collection, and analysis, were performed by all authors. The first draft of the manuscript was written by T.M.C., N.A.V., and E.A.R.M. All authors commented on previous versions of the manuscript and read and approved the final manuscript. Other declarations To study the native species Galactia lindenii , the contract code for access to genetic resources granted by the Ministry of Environment and Sustainable Development of Colombia was number 246. Ethical approval The study was carried out following the approval of the Research Ethics Committee at Universidad Nacional de Colombia (Protocol INC GT00035). Informed consent was obtained from all patients before collecting samples for analysis. This research was classified as a minimal-risk study following the guidelines outlined in the document "RESOLUCIÓN 8430 DE 1993" on Ethical Aspects of Human Research (Title II, Chapter 1) published by the Ministry of Health of Colombia.. The samples from the analyses outlined in this project were handled according to the biosafety protocols endorsed by the national and international scientific community, as regulated by the Ministry of Social Protection of Colombia in the Resolution 8430 of 1993. References De Coninck, T., Van Damme, E.J.M.: Review: The multiple roles of plant lectins. Plant. Sci. 313 (2021). https://doi.org/10.1016/j.plantsci.2021.111096 . Verkerke, H., Dias-Baruffi, M., Cummings, R.D., Arthur, C.M., Stowell, S.R.: Galectins: An Ancient Family of Carbohydrate Binding Proteins with Modern Functions. In: Stowell, S.R., Arthur, C.M., Cummings, R.D. (eds.) Galectins. Methods in Molecular Biology, vol 2442, pp 1–40. Humana, New York, NY (2022). https://doi.org/10.1007/978-1-0716-2055-7_1 . André, S., Kaltner, H., Manning, J.C., Murphy, P.V., Gabius, H.J.: Lectins: getting familiar with translators of the sugar code. Molecules. 20(2):1788–1823 (2015). https://doi.org/10.3390/molecules20021788 . Mishra, A., Behura, A., Mawatwal, S., Kumar, A., Naik, L., Mohanty, S.S., Manna, D., Dokania, P., Mishra, A.: Structure-function and application of plant lectins in disease biology and immunity. Food. Chem. Toxicol. 134 (2019). https://doi.org/10.1016/j.fct.2019.110827 . Mattox, D.E., Baiyley-Kellogg, C.: Comprehensive analysis of lectin-glycan interactions reveals determinants of lectin specificity. Plos. Comput. Biol. (2021). https://doi.org/10.1371/journal.pcbi.1009470 . Cummings, R.D., Etzler, M.E., Hahn, M.G., Darvil, A., Godula, K., Woods, R.J., Mahal, L.K.: Glycan-Recognizing Probes as Tools. In: Varki, A., Cummings, R.D., Esko, J.D., Stanley, P., Hart, G.W., Aebi, M., Mohnen, D., Kinoshita, T., Packer, N.H., Prestegard, J.H., Schnaar, R.L., Seeberger, P.H., (eds.) Essentials of Glycobiology. 4th ed, Chap. 48. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press (2022). https://www.ncbi.nlm.nih.gov/books/NBK579992/ . Cummings, R.D., Pierce, J.M.: The challenge and promise of glycomics. Chem. Biol. 21(1):1–15 (2014). https://doi.org/10.1016/j.chembiol.2013.12.010 . Haab, B.B., Klamer. Z.: Advances in Tools to Determine the Glycan-Binding Specificities of Lectins and Antibodies. Mol. Cell. Proteomics. 19(2):224–232 (2020). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000120/ Galili, U.: Human Natural Antibodies to Mammalian Carbohydrate Antigens as Unsung Heroes Protecting against Past, Present, and Future Viral Infections. Antibodies (Basel). 9(2):25 (2020). https://doi.org/10.3390/antib9020025 . Iskratsch, T., Braun, A., Paschinger, K., Wilson, I.B.H.: Specificity analysis of lectins and antibodies using remodeled glycoproteins. Anal. Biochem. 386(2):133–146 (2009). https://doi.org/10.1016/j.ab.2008.12.005 . Zhou, D., Xu, L., Huang, W., Tonn, T.: Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy. Molecules. 23(6):1326 (2018). https://doi.org/10.3390/molecules23061326 . Mollicone, R., Cailleau, A., Imberty, A., Gane, P., Perez, S., Oriol, R.: Recognition of the blood group H type 2 trisaccharide epitope by 28 monoclonal antibodies and three lectins. Glycoconj. J. 13(2):263–271 (1996). https://doi.org/10.1007/BF00731501 . Collins, B.C., Gunn, R.J., McKitrick, T.R., Cummings, R.D., Cooper, M.D., Herrin, B.R., Wilson, I.A.: Structural Insights into VLR Fine Specificity for Blood Group Carbohydrates. Structure. 25(11):1667–1678. E4. (2017). https://doi.org/10.1016/j.str.2017.09.003 . Kappler, K., Hennet, T.: Emergence and significance of carbohydrate-specific antibodies. Genes. Immun. 21, 224–239 (2020). https://www.nature.com/articles/s41435-020-0105-9 . Dang, K., Zhang, W., Jiang, S., Lin, X., Qian, A.: Application of lectin microarrays for biomarker discovery. ChemistryOpen. 9(3):285–300 (2020). https://doi.org/10.1002/open.201900326 . Bojar, D., Meche, L., Meng, G., Eng, E., Smith, D.F., Cummings, R.D., Mahal, L.K.: A Useful Guide to Lectin Binding: Machine-Learning Directed Annotation of 57 Unique Lectin Specificities. ACS Chem. Biol. 17(11):2993–3012 (2022). https://doi.org/10.1021/acschembio.1c00689 Defaus, S., Gupta, P., Andreu, D., Gutiérrez-Gallego, R.: Mammalian protein glycosylation–structure versus function. Analyst. 139(12):2944–2967 (2014). https://doi.org/10.1039/C3AN02245E . Ogawa, R., Okimoto, T., Kodama, M., Togo, K., Fukuda, K., Okamoto, K., Mizukami, K., Murakami, K.: Changes in Gastric Mucosal Glycosylation Before and After Helicobacter pylori Eradication Using Lectin Microarray Analysis. Turk. J. Gastroenterol. 33(2):88–94 (2022). https://doi.org/10.5152/tjg.2021.201116 . Liang, Y., Han, P., Wang, T., Ren, H., Gao, L., Shi, P., Zhang, S., Yang, A., Li, Z., Chen, M.: Stage-associated differences in the serum N- and O-glycan profiles of patients with non-small cell lung cancer. Clin. Proteomics. 16:20 (2019). https://doi.org/10.1186/s12014-019-9240-6 Fukushima, K., Satoh, T., Baba, S., Yamashita, K.: alpha1,2-Fucosylated and beta-N-acetylgalactosaminylated prostate-specific antigen as an efficient marker of prostatic cancer. Glycobiology. 20(4):452–460 (2010). https://doi.org/10.1093/glycob/cwp197 . Tokuda, N., Zhang, Q., Yoshida, S., Kusunoki, S., Urano, T., Furukawa, K., Furukawa, K.: Genetic mechanisms for the synthesis of fucosyl GM1 in small cell lung cancer cell lines. Glycobiology. 16(10): 916–925 (2006). https://doi.org/10.1093/glycob/cwl022 . Tkac, J., Gajdosova, V., Hroncekova, S., Bertok, T., Hires, M., Jane, E., Lorencova, L., Kasak, P.: Prostate-specific antigen glycoprofiling as diagnostic and prognostic biomarker of prostate cancer. Interface. Focus. 9(2):20180077 (2019). http://doi.org/10.1098/rsfs.2018.0077 . Huang, W.L., Li, Y.G., Lv, Y.C., Guan, X.H., Ji, H.F., Chi, B.R.: Use of lectin microarray to differentiate gastric cancer from gastric ulcer. World. J. Gastroenterol. 20(18):5474–5482 (2014). http://dx.doi.org/10.3748/wjg.v20.i18.5474 . Duarte, H.O., Rodrigues, J.G., Gomes, C., Hensbergen, P.J., Ederveen, A.L.H, de Ru, A.H., Mereiter, S., Polónia, A., Fernandes, E., Ferreira, J.A., van Veelen, P.A., Santos, L.L., Wuhrer, M., Gomes, J., Reis, C.A.: ST6Gal1 targets the ectodomain of ErbB2 in a site-specific manner and regulates gastric cancer cell sensitivity to trastuzumab. Oncogene. 40(21):3719–3733 (2021). https://doi.org/10.1038/s41388-021-01801-w . Gomes, C., Almeida, A., Barreira, A., Calheiros, J., Pinto, F., Abrantes, R., Costa, A., Polonia, A., Campos, D., Osório, H., Sousa, H., Pinto-de-Sousa, J., Kolarich, D., Reis, C.A.: Carcinoembryonic antigen carrying SLe X as a new biomarker of more aggressive gastric carcinomas. Theranostics. 9(24):7431–7446 (2019). https://doi.org/10.7150/thno.33858 . Aziz, F., Khan, I., Shukla, S., Dey, D.K., Yan, Q., Chakraborty, A., Yoshitomi, H., Hwang, S.K., Sonwal, S., Lee, H., Haldorai, Y., Xiao, J., Huh, Y.S., Bajpai, V.K., Han, Y.K.: Partners in crime: The Lewis Y antigen and fucosyltransferase IV in Helicobacter pylori-induced gastric cancer. Pharmacol. Ther. 232:107994 (2022). https://doi.org/10.1016/j.pharmthera.2021.107994 . Hayashi, Y., Yimiti, D., Sanada, Y., Ding, C., Omoto, T., Ogura, T., Nakasa, T., Ishikawa, M., Hiemori, K., Tateno, H., Miyaki, S., Adachi, N.: The therapeutic capacity of bone marrow MSC-derived extracellular vesicles in Achilles tendon healing is passage-dependent and indicated by specific glycans. FEBS. Lett. 596(8):1047–1058 (2022). https://doi.org/10.1002/1873-3468.14333 . Xu, Y., Huo, J., Nie, R., Ge, L., Xie, C., Meng, Y., Liu, J., Wu, L., Qin, X.: Altered profile of glycosylated proteins in serum samples obtained from patients with Hashimoto's thyroiditis following depletion of highly abundant proteins. Front. Immunol. 14:1182842 (2023). https://www.frontiersin.org/articles/ 10.3389/fimmu.2023.1182842/full de Queiroz, L.P., Pastore, J.F., Cardoso, D., Snak, C., de C Lima, A.L., Gagnon, E., Vatanparast, M., Holland, A.E., Egan, A.N.: A multilocus phylogenetic analysis reveals the monophyly of a recircumscribed papilionoid legume tribe Diocleae with well-supported generic relationships. Mol. Phylogenet. Evol. 90:1–19 (2015). https://doi.org/10.1016/j.ympev.2015.04.016 . Almanza, M., Vega, N., Pérez, G.: Isolating and characterising a lectin from Galactia lindenii seeds that recognises blood group H determinants. Arch. Biochem. Biophys. 429(2):180–190 (2004). http://dx.doi.org/10.1016/j.abb.2004.06.010 . Quintero, M.: Elucidación parcial de la estructura primaria de la lectina LGL-P2 y purificación y caracterización parcial de la lectina LGL-P4 presentes en semillas de Galactia lindenii. Tesis de Maestría, Facultad de Ciencias, Departamento de Química, Universidad Nacional de Colombia. Sede Bogotá. (2014). https://repositorio.unal.edu.co/handle/unal/51820 . Cortázar, T.M., Wilson, I.B.H., Hykollari, A., Reyes, E.A., Vega, N.A.: Differential recognition of natural and remodeled glycotopes by three Diocleae lectins. Glycoconj. J. 35(2):205–216 (2018). https://doi.org/10.1007/s10719-018-9851-6 . Pérez, G.: Isolation and characterization of a novel lectin from Dioclea lehmanni (Fabaceae) seeds. Int. J. Biochem. Cell. Biol. 30:843–853 (1998). https://doi.org/10.1016/S1357-2725(98)00045-4 . Melgarejo, L.M., Vega, N., Pérez, G.: Isolation and characterization of novel lectins from Canavalia ensiformis DC and Dioclea grandiflora Mart. Ex Benth. seeds. Braz. J. Plant. Physiol. 17(3): 315–324 (2005). https://doi.org/10.1590/S1677-04202005000300006 . Dam, T.K., Cavada, B.S., Nagano, C.S., Rocha, B.A., Benevides, R.G., Nascimento, K.S., de Sousa, L.A., Oscarson, S., Brewer, C.F.: Fine specificities of two lectins from Cymbosema roseum seeds: a lectin specific for high-mannose oligosaccharides and a lectin specific for blood group H type II trisaccharide. Glycobiology. 21(7):925–933 (2011). https://doi.org/10.1093/glycob/cwr025 . Cavada, B.S., Pinto-Junior, V.R., Osterne, V.J.S., Lossio, C.F., Silva, M.T.L., Correia, J.L.A., Correia, S.E.G., Nagano, C.S., Oliveira, M.V., Lima, L.D., Vital, A.P.M.S., Leal, R.B., Nascimento, K.S.: A Diocleinae type II lectin from Dioclea lasiophylla Mart. Ex Benth seeds specific to α-lactose/GalNAc. Process. Biochem. 93, 104–114 (2020). https://doi.org/10.1016/j.procbio.2020.03.026 . Rocha, B.A.M., Moreno, F.B.M.B, Delatorre, P., Souza, E.P., Marinho, E.S., Benevides, R.G., Rustiguel, J.K.R., Souza, L.A.G., Nagano, C.S., Debray, H., Sampaio, A.H., de Azevedo Jr, W.F., Cavada, B.S.: Purification, characterization, and preliminary X-ray diffraction analysis of a lactose-specific lectin from Cymbosema roseum seeds. Appl. Biochem. Biotechnol. 152(3):383–393 (2009). https://doi.org/10.1007/s12010-008-8334-9 . Batista, F.A.H, Goto, L.S., Garcia, W., Moraes, D.I., Neto, M.O., Polikarpov, I., Cominetti, M.R., Selistre-de-Araújo, H.S., Beltramini, L.M., Araujo, A.P.U.: Camptosemin, a tetrameric lectin of Camptosema ellipticum: structural and functional analysis. Eur Biophys J. 39(8):1193–1205 (2010). https://link.springer.com/article/ 10.1007/s00249-009-0571-5 . Pérez, G., Hernández, M., Mora, E.: Isolation and characterization of a lectin from the seeds of Dioclea lehmanni. Phytochem. 29(6):1745–1749 (1990). https://doi.org/10.1016/0031-9422(90)85007-3 . Dam, T.K., Cavada, B.S., Grangeiro, T.B., Santos, C.F., de Sousa, F.A., Oscarson, S., Brewer, C.F.: Diocleinae lectins are a group of proteins with conserved binding sites for the core trimannoside of asparagine-linked oligosaccharides and differential specificities for complex carbohydrates. J. Biol. Chem. 273(20):12082–12088 (1998). https://doi.org/10.1074/jbc.273.20.12082 Calvete, J.J., Thole, H.H., Raida, M., Urbanke, C., Romero, A., Grangeiro, T.B., Ramos, M.V., Almeida da Rocha, I.M., Guimarães, F.N., Cavada, B.S.: Molecular characterization and crystallization of Diocleinae lectins. Biochim. Biophys. Acta. 1430(2):367–375 (1999). doi: 10.1016/s0167-4838(99)00020-5 Hermanson, G.T.: Immobilization of Ligands on Chromatography Supports. In: Audet, J., Preap, M. (eds.) Bioconjugate Techniques Third Edition. Elsevier, London, UK (2013). http://dx.doi.org/10.1016/B978-0-12-382239-0.00015-7 . Smith, P.K., Krohn, R.I., Hermanson, G.T., Mallia, A.K., Gartner, F.H., Provenzano, M.D., Fujimoto, E.K., Goeke, N.M., Olson, B.J., Klenk, D.C.: Measurement of protein using Bicinchoninic Acid. Anal. Biochem. 150:76–85 (1985). https://doi:10.1016/0003-2697(85)90442-7 . Laemmli, U. K.: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 227(5259): 680–685 (1970). https://doi.org/10.1038/227680a0 Iglesias, J.L., Lis, H., Sharon, N.: Purification and Properties of a D-Galactose/N-Acetyl-D-galactosamine-Specific Lectin from Erythrina cristagalli. Eur. J. Biochem. 123(2):247–252 (1982). https://doi.org/10.1111/j.1432-1033.1982.tb19760.x . Hirohashi, S., Clausen, H., Yamada, T., Shimosato, Y., Hakomori, S.: Blood group A cross-reacting epitope defined by monoclonal antibodies NCC-LU-35 and – 81 expressed in cancer of blood group O or B individuals: its identification as Tn antigen. Proc. Natl. Acad. Sci. USA. 82(20):7039–7043 (1985). https://doi.org/10.1073/pnas.82.20.7039 . Koizumi, T., Matsumoto-Takasaki, A., Nakada, H., Nakata, M., Fujita-Yamaguchi, Y.: Preparation of asialo-agalacto-glycophorin A for screening of anti-Tn antibodies. BioSci. Trends. 4(6):308–311 (2010). Wu, A.M., Duk, M., Lin, M., Broadberry, R.E., Lisowska, E.: Identification of variant glycophorins of human red cells by lectinoblotting: Application to the Mi. III variant that is relatively frequent in the Taiwanese population. Transfusion. 35(7):571–576 (1995). https://doi.org/10.1046/j.1537-2995.1995.35795357879.x Evans, S.V., MacKenzie, C.R.: Characterization of protein-glycolipid recognition at the membrane bilayer. J. Mol. Recognit. 12(3): 155–168 (1999). https://doi.org/10.1002/(SICI)1099-1352(199905/06)12:33.0.CO;2-S . Stanley, P., Wuhrer, M., Lauc, G., Stowell, S.R., Cummings, R.D.: Structures Common to Different Glycans. In: Varki, A., Cummings, R.D., Esko, J.D., Stanley, P., Hart, G.W., Aebi, M., Mohnen, D., Kinoshita, T., Packer, N.H., Prestegard, J.H., Schnaar, R.L., Seeberger, P.H, (eds.) Essentials of Glycobiology [Internet]. 4th Edition. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press (2022), Chap. 14. https://doi.org/10.1101/glycobiology.4e.1 Dean, L.: The ABO blood group. In: Blood Groups and Red Cell Antigens [Internet]. Bethesda (MD): National Center for Biotechnology Information (US) (2005), Chap. 5. https://www.ncbi.nlm.nih.gov/books/NBK2267/ Aoki, T.: A Comprehensive Review of Our Current Understanding of Red Blood Cell (RBC) Glycoproteins. Membranes (Basel). 7(4):56 (2017). https://doi.org/10.3390/membranes7040056 . Ogawa, H., Galili, U.: Profiling terminal N-acetyllactosamines of glycans on mammalian cells by an immuno-enzymatic assay. Glycoconj. J. 23(9):663–674 (2006). https://doi.org/10.1007/s10719-006-9005-0 . Ito, T., Suzuki, Y., Mitnaul, L., Vines, A., Kida, H., Kawaoka, Y.: Receptor specificity of influenza A viruses correlates with the agglutination of erythrocytes from different animal species.Virology. 227(2):493–499 (1997). https://doi.org/10.1006/viro.1996.8323 Altman, M.O., Gagneux, P.: Absence of Neu5Gc and Presence of Anti-Neu5Gc Antibodies in Humans-An Evolutionary Perspective. Front. Immunol. 10:789 (2019). https://doi.org/10.3389/fimmu.2019.00789 . Sreenivasan, C.C., Sheng, Z., Wang, D., Li, F.: Host Range, Biology, and Species Specificity of Seven-Segmented Influenza Viruses-A Comparative Review on Influenza C and D. Pathogens. 10(12):1583 (2021). https://doi.org/10.3390/pathogens10121583 . Yamamoto, T., Hara, H., Iwase, H., Jagdale, A., Bikhet, M.H., Morsi, M.A., Cui, Y., Nguyen, H.Q., Wang, Z.Y., Anderson, D.J., Foote, J., Schuurman, H.J., Ayares, D., Eckhoff, D.E., Cooper, D.KC.: The final obstacle to successful pre-clinical xenotransplantation? Xenotransplantation. 27(5):e12596 (2020). https://doi.org/10.1111/xen.12596 . Feizi, T.: Demonstration by monoclonal antibodies that carbohydrate structures of glycoproteins and glycolipids are onco-developmental antigens. Nature. 314, 53–57 (1985). https://doi.org/10.1038/314053a0 . Schneider, M., Al-Shareffi, E., Haltiwanger, R.S.: Biological functions of fucose in mammals. Glycobiology. 27(7):601–618 (2017). https://doi.org/10.1093/glycob/cwx034 . Ravn, V., Dabelsteen, E.: Tissue distribution of histo-blood group antigens. APMIS. 108(1):1–28 (2000). https://doi.org/10.1034/j.1600-0463.2000.d01-1.x . Wu, F., Qin, Y., Jiang, Q., Zhang, J., Li, F., Li, Q., Wang, X., Gao, Y., Miao, J., Guo, C., Yang, Y., Ni, L., Liu, L., Zhang, S., Huang C.: MyoD1 suppresses cell migration and invasion by inhibiting FUT4 transcription in human gastric cancer cells. Cancer. Gene. Ther. 27(10–11):773–784 (2020). https://doi.org/10.1038/s41417-019-0153-3 . Chessa, D., Winter, M.G., Jakomin, M., Bäumler, A.J.: Salmonella enterica serotype Typhimurium Std fimbriae bind terminal alpha(1,2)fucose residues in the cecal mucosa. Mol. Microbiol. 71(4):864–875 (2009). https://doi.org/10.1111/j.1365-2958.2008.06566.x . Arenas, M.I., Royuela, M., Fraile, B., Paniagua, R., Wilhelm, B., Aumüller, G.: Identification of N- and O-linked oligosaccharides in human seminal vesicles. J. Androl. 22(1):79–87 (2001). https://doi.org/10.1002/j.1939-4640.2001.tb02156.x . Dall’Olio, F., Pucci, M., Malagolini, N.: The Cancer-Associated Antigens Sialyl Lewis a/x and Sd a : Two Opposite Faces of Terminal Glycosylation. Cancers. 13(21):5273 (2021). https://doi.org/10.3390/cancers13215273 . Pinho, S., Reis, C.: Glycosylation in cancer: mechanisms and clinical implications. Nat. Rev. Cancer. 15(9):540–555 (2015). https://doi.org/10.1038/nrc3982 Thomas, D., Rathinavel, A.K., Radhakrishnan, P.: Altered glycosylation in cancer: A promising target for biomarkers and therapeutics. Biochim. Biophys. Acta. Rev. Cancer. 1875(1):188464 (2021). https://doi : 10.1016/j.bbcan.2020.188464 . Radovani, B., Gudelj, I.: N-Glycosylation and Inflammation; the Not-So-Sweet Relation. Front. Immunol. 13: 893365 (2022). https://www.frontiersin.org/articles/ 10.3389/fimmu.2022.893365/full Reily, C., Stewart, T.J., Renfrow, M.B., Novak, J.: Glycosylation in health and disease. Nat. Rev. Nephrol. 15(6): 346–366 (2019). https://www.nature.com/articles/s41581-019-0129-4 Zhou, X., Motta, F., Selmi, C., Ridgway, W.M., Gershwin, M.E., Zhang, W.: Antibody Glycosylation in Autoimmune Diseases. Autoimmun. Rev. 20(5):102804 (2021). https://doi.org/10.1016/j.autrev.2021.102804 Gabius, H.J., Kaltner, H., Kopitz, J., André, S.: The glycobiology of the CD system: a dictionary for translating marker designations into glycan/lectin structure and function. Trends. Biochem. Sci. 40(7):360–376 (2015). https://doi.org/10.1016/j.tibs.2015.03.013 . www.functionalglycomics. org/static/consortium/Nomenclature.shtml . Accessed 20 January 2023. Schjoldager, K.T., Narimatsu, Y., Joshi, H.J., Clausen, H.: Global view of human protein glycosylation pathways and functions. Nat. Rev. Mol. Cell. Biol. 21(12):729–749 (2020). https://www.nature.com/articles/s41580-020-00294-x Vajaria, B.N., Patel, P.S.: Glycosylation: a hallmark of cancer?. Glycoconj. J. 34(2):147–156 (2017). https://link.springer.com/article/10.1007/s 10719-016-9755-2 Hollander, N., Haimovich, J.: Altered N-Linked Glycosylation in Follicular Lymphoma and Chronic Lymphocytic Leukemia: Involvement in Pathogenesis and Potential Therapeutic Targeting. Front. Immunol. 8:912 (2017). https://www.frontiersin.org/articles/ 10.3389/fimmu.2017.00912/full Bastian, K., Scott, E., Elliott, D.J., Munkley. J.: FUT8 Alpha-(1,6)-Fucosyltransferase in Cancer. Int. J. Mol. Sci. 22(1):455 (2021). https://www.mdpi.com/1422-0067/22/1/455 Broekhuis, J.M., James, B.C., Cummings, R.D., Hasselgren, P.O.: Posttranslational Modifications in Thyroid Cancer: Implications for Pathogenesis, Diagnosis, Classification, and Treatment. Cancers (Basel). 14(7):1610 (2022). https://www.mdpi.com /2072-6694/14/7/1610 González-Cámpora, R., Sanchez Gallego, F., Martin Lacave, I., Mora Marin, J., Montero Linares, C., Galera-Davidson, H.: Lectin histochemistry of the thyroid gland. Cancer. 62(11):2354–2362 (1988). https://doi.org/10.1002/1097-0142(19881201)62:113.0.CO;2-D Audette, G.F., Olson, D.J.H., Ross, A.R.S., Quail, J.W., Delbaere, L.T.J.: Examination of the structural basis for O(H) blood group specificity by Ulex europaeus Lectin I. Canadian. J. Chem. 80(8) (2002). https://doi.org/10.1139/v02-134 . Gao, C., Hanes, M.S., Byrd-Leotis, L.A., Wei, M., Jia, N., Kardish, R.J., McKitrick, T.R., Steinhauer, D.A., Cummings, R.D.: Unique Binding Specificities of Proteins toward Isomeric Asparagine-Linked Glycans. Cell. Chem. Biol. 26(4):535–547.e4 (2019). https://doi:10.1016/j.chembiol.2019.01.002 . Yamashita, K., Ohkura, T., Umetsu, K., Suzuki, T.: Purification and characterization of a Fuc alpha 1–>2Gal beta 1–> and GalNAc beta 1–>-specific lectin in root tubers of Trichosanthes japonica. J. Biol. Chem. 267(35):25414–25422 (1992). Prete, A., Borges de Souza, P., Censi, S., Muzza, M., Nucci, N., Sponziello, M.: Update on Fundamental Mechanisms of Thyroid Cancer. Front. Endocrinol. (Lausanne). 11:102 (2020). https://www.frontiersin.org/articles/ 10.3389/fendo.2020.00102/full Bikas, A., Burman, K.D.: Epidemiology of thyroid cancer: a comprehensive guide for the clinician. In: The Thyroid and Its Diseases. 541–547 (2019). doi: 10.1007/978-3-319-72102-6_35 Basolo, F., Macerola, E., Poma, A.M., Torregrossa, L.: The 5th edition of WHO classification of tumors of endocrine organs: changes in the diagnosis of follicular-derived thyroid carcinoma. Endocrine. 80(3):470–476 (2023). https://link.springer.com/article/ 10.1007/s12020-023-03336-4 Baloch, Z.W., Asa, S.L., Barletta, J.A., Ghossein, R.A., Juhlin, C.C., Jung, C.K., LiVolsi, V.A., Papotti, M.G., Sobrinho-Simões, M., Tallini, G., Mete, O.: Overview of the 2022 WHO Classification of Thyroid Neoplasms. Endocr. Pathol. 33(1):27–63 (2022). https://link.springer.com/article/ 10.1007/s12022-022-09707-3 Koçak, Ö.F., Kayili, H.M., Albayrak, M., Yaman, M.E., Kadıoğlu, Y., Salih, B.: N-glycan profiling of papillary thyroid carcinoma tissues by MALDI-TOF-MS. Anal. Biochem. 584:113389 (2019). doi: 10.1016/j.ab.2019.113389 . Cao, Z., Zhang, Z., Liu, R., Wu, M., Li, Z., Xu, X., Liu, Z.: Serum Linkage-Specific Sialylation Changes Are Potential Biomarkers for Monitoring and Predicting the Recurrence of Papillary Thyroid Cancer Following Thyroidectomy. Front. Endocrinol (Lausanne). 13:858325 (2022). https://www.frontiersin.org/articles/ 10.3389/fendo.2022.858325/full Zhang, Z., Reiding, K.R., Wu, J., Li, Z., Xu, X.: Distinguishing Benign and Malignant Thyroid Nodules and Identifying Lymph Node Metastasis in Papillary Thyroid Cancer by Plasma N -Glycomics. Front. Endocrinol. (Lausanne). 12:692910 (2021). https://www.frontiersin.org/articles/ 10.3389/fendo.2021.692910/full Shimizu, K., Nakamura, K., Kobatake, S., Satomura, S., Maruyama, M., Kameko, F., Tajiri, J., Kato, R.: The clinical utility of Lens culinaris agglutinin-reactive thyroglobulin ratio in serum for distinguishing benign from malignant conditions of the thyroid. Clin. Chim. Acta. 379(1–2):101–104 (2007). doi: 10.1016/j.cca.2006.12.017 . Tarutani, O., Ui, N.: Properties of thyroglobulins from normal thyroid and thyroid tumor on a concanavalin A-sepharose column. J. Biochem. 98(3):851–857 (1985). https://doi.org/10.1093/oxfordjournals.jbchem.a135344 . Ząbczyńska, M., Kozłowska, K., Pocheć, E.: Glycosylation in the Thyroid Gland: Vital Aspects of Glycoprotein Function in Thyrocyte Physiology and Thyroid Disorders. Int. J. Mol. Sci. 19(9):2792 (2018). https://doi.org/10.3390/ijms19092792 Zhan, X.X., Zhao, B., Diao, C., Cao, Y., Cheng, R.C.: Expression of MUC1 and CD176 (Thomsen-Friedenreich antigen) in Papillary Thyroid Carcinomas. Endocr. Pathol. 26(1):21–26 (2015). https://doi-org.ezproxy.unal.edu.co/ 10.1007/s12022-015-9356-9 . Sun, X., Tie, H.C., Chen, B., Lu, L.: Glycans function as a Golgi export signal to promote the constitutive exocytic trafficking. J. Biol. Chem. 295(43):14750–14762 (2020). https://www.jbc.org/article/S0021- 9258(17)49351-3/fulltext Limaiem, F., Rehman, A., Anastasopoulou, C., Mazzoni, T.: Papillary Thyroid Carcinoma. [Updated 2023 Jan 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. Available from: https://www.ncbi.nlm.nih.gov/books/NBK536943/ Kamma, H., Kameyama, K., Kondo, T., Imamura, Y., Nakashima, M., Chiba, T., Hirokawa, M.: Pathological diagnosis of general rules for the description of thyroid cancer by Japanese Society of Thyroid Pathology and Japan Association of Endocrine Surgery. Endocr. J. 69(2):139–154 (2022). https://www.jstage.jst.go.jp/article/endocrj/69/2/69_EJ 21-0388/_article Vowden, P., Lowe, A.D., Lennox, E.S., Bleehen NM.: Thyroid blood group isoantigen expression: a parallel with ABH isoantigen expression in the distal colon. Br. J. Cancer. 53(6):721–725 (1986). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2001419/ Ito, N., Yokota, M., Nagaike, C., Morimura, Y., Hatake, K., Matsunaga, T.: Histochemical demonstration and analysis of poly-N-acetyllactosamine structures in normal and malignant human tissues. Histol. Histopathol. 11(1):203–214 (1996). Ito, N., Yokota, M., Nagaike, C., Morimura, Y., Hatake, K., Tanaka, O., Matsunaga, T.: Simultaneous expression of keratan sulphate epitope (a sulphated poly-N-acetyllactosamine) and blood group ABH antigens in papillary carcinomas of the human thyroid gland. Histochem. J. 28(9):613–623 (1996). https://link.springer.com/article/ 10.1007/BF02331382 Fonseca, E., Castanhas, S., Sobrinho-Simoes, M.: Expression of Simple Mucin Type Antigens and Lewis Type 1 and Type 2 Chain Antigens in the Thyroid Gland: An Immunohistochemical Study of Normal Thyroid Tissues, Benign Lesions, and Malignant Tumors. Endocr. Pathol. 7(4):291–301 (1996). https://link.springer.com/article/ 10.1007/BF02739836 Ito, Y., Miyauchi, A., Yoshida, H., Uruno, T., Nakano, K., Takamura, Y., Miya, A., Kobayashi, K., Yokozawa, T., Matsuzuka, F., Taniguchi, N., Matsuura, N., Kuma, K., Miyoshi, E.: Expression of alpha1,6-fucosyltransferase (FUT8) in papillary carcinoma of the thyroid: its linkage to biological aggressiveness and anaplastic transformation. Cancer. Lett. 200(2):167–172 (2003). doi: 10.1016/s0304-3835(03)00383-5 . Sancakli, A., Kaptan, E.: Lectin Treatment Affects Malignant Characteristics of TPC-1 Papillary Thyroid Cancer Cells. Eur. J. Biol. 78(1): 51–57 (2019). doi: 10.26650/EurJBiol.2019.0006 González-Cámpora, R., García-Sanatana, J.A., Jordà i Heras, M.M., Salaverri, C.O., Vázquez-Ramírez, F.J., Argueta-Manzano, O.E., Galera-Davidson, H.: Blood group antigens in differentiated thyroid neoplasms. Arch. Pathol. Lab. Med. 122(11):957–965 (1998). Peng, Y., Zhan, X.X., Cao, Y., Zhang, H.W., Cao, W.H., Su, Y.J., Diao, C., Sun, Q.M., Cheng, R.C.: The Potential Action of Thomsen-Friedenreich Monoclonal Antibody (A78-G/A7) in Thyroid Cancer. Onco. Targets. Ther. 13:8677–8689 (2020). https://doi.org/10.2147/OTT.S261685 Vijayakumar, T., Augustine, J., Mathew, L., Aleykutty, M.A., Nair, M.B., Remani, P., Nair, M.K.: Tissue binding pattern of plant lectins in benign and malignant lesions of thyroid. J. Exp. Pathol. 6(1–2):11–23 (1992). Sarker, A.B., Akagi, T., Teramoto, N., Nose, S., Yoshino, T., Kondo, E.: Bauhinia purpurea (BPA) binding to normal and neoplastic thyroid glands. Pathol. Res. Pract. 190(11):1005–1011 (1994). https://doi.org/10.1016/S0344-0338(11)80894-0 . Vecchio, G., Parascandolo, A., Allocca, C., Ugolini, C., Basolo, F., Moracci, M., Strazzulli, A., Cobucci-Ponzano, B., Laukkanen, M.O., Castellone, M.D., Tsuchida, N.: Human a-L-fucosidase-1 attenuates the invasive properties of thyroid cancer. Oncotarget. 8(16):27075–27092 (2017). doi: 10.18632/oncotarget.15635 . Kaltner, H., Gabius, H.J.: Sensing Glycans as Biochemical Messages by Tissue Lectins: The Sugar Code at Work in Vascular Biology. Thromb. Haemost. 119(4):517–533 (2019). doi: 10.1055/s-0038-1676968 . Jung, J.Y., Oh, J.H., Lee, D.H., Lee, S., Chung, J.H.: Blood type B antigen modulates cell migration through regulating cdc42 expression and activity in HaCaT cells. J. Cell. Physiol. 228(11):2243–2251 (2013). doi: 10.1002/jcp.24393 . Tsuchida, N., Ikeda, M.A., Ιshino, Υ., Grieco, M., Vecchio, G.: FUCA1 is induced by wild-type p53 and expressed at different levels in thyroid cancers depending on p53 status. Int. J. Oncol. 50(6):2043–2048 (2017). doi: 10.3892/ijo.2017.3968 . Lin, W.M., Karsten, U., Goletz, S., Cheng, R.C., Cao, Y.: Co-expression of CD173 (H2) and CD174 (Lewis Y) with CD44 suggests that fucosylated histo-blood group antigens are markers of breast cancer-initiating cells. Virchows. Arch. 456(4):403–409 (2010). doi: 10.1007/s00428-010-0897-5 . Hautala, L.C., Pang, P.C., Antonopoulos, A., Pasanen, A., Lee, C.L., Chiu, P.C.N., Yeung, W.S.B., Loukovaara, M., Bützow, R., Haslam, S.M., Dell, A., Koistinen, H.: Altered glycosylation of glycodelin in endometrial carcinoma. Lab. Invest. 100(7):1014–1025 (2020). doi: 10.1038/s41374-020-0411-x . Larena, A., Vierbuchen, M., Fischer, R.: Blood group antigen expression in malignant tumors of the thyroid: a parallel between medullary and nonmedullary carcinomas. Langenbecks. Arch. Chir. 380(5):269–272 (1995). doi: 10.1007/BF00184101 . Säljö, K., Thornell, A., Jin, C., Norlén, O., Teneberg, S.: Characterization of Human Medullary Thyroid Carcinoma Glycosphingolipids Identifies Potential Cancer Markers. Int. J. Mol. Sci. 22(19):10463 (2021). https://www.mdpi.com/ 1422-0067/22/19/10463 Blanas, A., Sahasrabudhe, N.M., Rodriguez, E., van Kooyk, Y., van Vliet, S.J.: Fucosylated Antigens in Cancer: An Alliance toward Tumor Progression, Metastasis, and Resistance to Chemotherapy. Front. Oncol. 8, 39 (2018). Adhikari, E., Liu, Q., Burton, C., Mockabee-Macias, A., Lester, D.K., Lau, E.: L-fucose, a sugary regulator of antitumor immunity and immunotherapies. Mol. Carcinog. 61(5):439–453 (2022). doi: 10.1002/mc.23394 . Fu, J., Guo, Q., Feng, Y., Cheng, P., Wu, A.: Dual role of fucosidase in cancers and its clinical potential. J. Cancer. 13(10):3121–3132 (2022). doi: 10.7150/jca.75840 . Lai, T.Y., Chen, I.J., Lin, R.J.,, G.S., Yeo, H.L., Ho, C.L., Wu, J.C., Chang, N.C., Lee, A.C., Yu, A.L.: Fucosyltransferase 1 and 2 play pivotal roles in breast cancer cells. Cell. Death. Discov. 5, 74 (2019). https://doi.org/10.1038/s41420-019-0145-y Keeley, T.S., Yang, S., Lau, E.: The Diverse Contributions of Fucose Linkages in Cancer. Cancers (Basel). 11(9):1241 (2019). doi: 10.3390/cancers11091241] . Zhang, Z., Sun, P., Liu, J., Fu, L., Yan, J., Liu, Y., Yu, L., Wang, X., Yan, Q.: Suppression of FUT1/FUT4 expression by siRNA inhibits tumor growth. Biochim. Biophys. Acta. 1783(2):287–296 (2008). doi: 10.1016/j.bbamcr.2007.10.007 . Ma, M., Fu, Y., Zhou, X., Guan, F., Wang, Y., Li, X.: Functional roles of fucosylated and O-glycosylated cadherins during carcinogenesis and metastasis. Cell. Signal. 63:109365 (2019). doi: 10.1016/j.cellsig.2019.109365 . Yokota, M., Ito, N., Hirota, T., Yane, K., Tanaka, O., Miyahara, H., Matsunaga, T.: Histochemical differences of the lectin affinities of backbone polylactosamine structures carrying the ABO blood group antigens in papillary carcinoma and other types of thyroid neoplasm. Histochem. J. 27(2):139–147 (1995). doi: 10.1007/BF00243909 . Vierbuchen, M., Schröder, S., Uhlenbruck, G., Ortmann, M., Fischer, R.: CA 50 and CA 19 – 9 antigen expression in normal, hyperplastic, and neoplastic thyroid tissue. Lab. Invest. 60(5):726–732 (1989). Vierbuchen, M., Larena, A., Schröder, S., Hanisch, F.G., Ortmann, M., Larena, A., Uhlenbruck, G., Fischer, R.: Blood group antigen expression in medullary carcinoma of the thyroid. An immunohistochemical study on the occurrence of type 1 chain-derived antigens. Virchows. Arch B Cell Pathol Incl Mol Pathol. 62(2):79–88 (1992). doi: 10.1007/BF02899668 . Cheng, S.P., Yang, P.S., Chien, M.N., Chen, M.J., Lee, J.J., Liu, CL.: Aberrant expression of tumor-associated carbohydrate antigen Globo H in thyroid carcinoma. J. Surg. Oncol. 114(7):853–858 (2016). Ito, N., Yokota, M., Kawahara, S., Nagaike, C., Morimura, Y., Hirota, T., Matsunaga, T.: Histochemical demonstration of different types of poly-N-acetyllactosamine structures in human thyroid neoplasms using lectins and endo-beta-galactosidase digestion. Histochem. J. 27(8):620–629 (1995). Khoury, E.L.: Reexpression of blood group ABH antigens on the surface of human thyroid cells in culture. J. Cell. Biol. 94(1):193–200 (1982). doi: 10.1083/jcb.94.1.193 . Dogan, O.: Evaluation of ABO/Rh blood group distributions in papillary thyroid cancer patients. Medicine (Baltimore). 102(32):e34564 (2023). doi: 10.1097/MD.0000000000034564 Grewal, R.K., Shaikh, A.R., Gorle, S., Kaur, M., Videira, P.A., Cavallo, L., Chawla, M.: Structural Insights in Mammalian Sialyltransferases and Fucosyltransferases: We Have Come a Long Way, but It Is Still a Long Way Down. Molecules. 26(17):5203 (2021). doi: 10.3390/molecules26175203 . Qin, H., Liu, J., Yu, M., Wang, H., Thomas, A.M., Li, S., Yan, Q., Wang, L.: FUT7 promotes the malignant transformation of follicular thyroid carcinoma through α-1,3-fucosylation of EGF receptor. Exp. Cell Res. 393:112095 (2020). doi: 10.1016/j.yexcr.2020.112095 . Karsten, U., Goletz, S.: What controls the expression of the core-1 (Thomsen-Friedenreich) glycotope on tumor cells? Biochemistry (Mosc). 80(7):801–807 (2015). doi: 10.1134/S0006297915070019 . Glinskii, O.V., Sud, S., Mossine, V.V., Mawhinney, T.P., Anthony, D.C., Glinsky, G.V., Pienta, K.J., Glinsky, V.V.: Inhibition of prostate cancer bone metastasis by synthetic TF antigen mimic/galectin-3 inhibitor lactulose-L-leucine. Neoplasia. 14(1):65–73 (2012). doi: 10.1593/neo.111544 . Saeland, E., Belo, A.I., Mongera, S., van Die, I., Meijer, G.A., van Kooyk, Y.: Differential glycosylation of MUC1 and CEACAM5 between normal mucosa and tumour tissue of colon cancer patients. Int. J. Cancer. 131(1):117–128 (2012). doi: 10.1002/ijc.26354 . Yu, L.G., Andrews, N., Zhao, Q., McKean, D., Williams, J.F., Connor, L.J., Gerasimenko, O.V., Hilkens, J., Hirabayashi, J., Kasai, K., Rhodes, J.M.: Galectin-3 interaction with Thomsen-Friedenreich disaccharide on cancer-associated MUC1 causes increased cancer cell endothelial adhesion. J. Biol. Chem. 282(1):773–781 (2007). doi: 10.1074/jbc.M606862200 . Glinsky, V.V., Glinsky, G.V., Rittenhouse-Olson, K., Huflejt, M.E., Glinskii, O.V., Deutscher, S.L., Quinn, TP.: The role of Thomsen-Friedenreich antigen in adhesion of human breast and prostate cancer cells to the endothelium. Cancer. Res. 61(12):4851–4857 (2001). Heimburg, J., Yan, J., Morey, S., Glinskii, O.V., Huxley, V.H., Wild, L., Klick, R., Roy, R., Glinsky, V.V., Rittenhouse-Olson, K.: Inhibition of spontaneous breast cancer metastasis by anti-Thomsen-Friedenreich antigen monoclonal antibody JAA-F11. Neoplasia. 8(11): 939–948 (2006). doi: 10.1593/neo.06493 . Chandler, K.B., Costello, C.E., Rahimi, N.: Glycosylation in the Tumor Microenvironment: Implications for Tumor Angiogenesis and Metastasis. Cells. 8(6):544 (2019). doi: 10.3390/cells8060544 . Cao, Y., Stosiek, P., Springer, G.F., Karsten, U.: Thomsen-Friedenreich-related carbohydrate antigens in normal adult human tissues: a systematic and comparative study. Histochem. Cell. Biol.106:197–207 (1996). Videira, P.A., Amado, I.F., Crespo, H.J., Algueró, M.C., Dall'Olio, F., Cabral, M.G., Trindade, H.: Surface alpha 2-3- and alpha 2-6-sialylation of human monocytes and derived dendritic cells and its influence on endocytosis. Glycoconj. J. 25(3):259–268 (2008). doi: 10.1007/s10719-007-9092-6 Cid, E., Yamamoto, M., Yamamoto, F.: Mixed-Up Sugars: Glycosyltransferase Cross-Reactivity in Cancerous Tissues and Their Therapeutic Targeting. Chembiochem. 23(5):e202100460 (2022). https://doi.org/10.1002/cbic.202100460 . Kurtenkov, O.: Profiling of Naturally Occurring Antibodies to the Thomsen-Friedenreich Antigen in Health and Cancer: The Diversity and Clinical Potential. Biomed. Res. Int. 2020:9747040 (2020). https://doi.org/10.1155/2020/9747040 Hoffmann, M., Hayes, M.R., Pietruszka, J., Elling, L.: Synthesis of the Thomsen-Friedenreich-antigen (TF-antigen) and binding of Galectin-3 to TF-antigen presenting neo-glycoproteins. Glycoconj. J. 37(4):457–470 (2020). doi: 10.1007/s10719-020-09926-y . Renaud, F., Gnemmi, V., Devos, P., Aubert, S., Crépin, M., Coppin, L., Ramdane, N., Bouchindhomme, B., d'Herbomez, M., Van Seuningen, I., Do Cao, C., Pattou, F., Carnaille, B., Pigny, P., Wémeau, J-L., Leteurtre, E.: Thyroid. 24(9):1375–1384 (2014). http://doi.org/10.1089/thy.2013.0594 Huang, D.H., Jin, L., Xie, W.W., Lin, Q., Chen, X.: Clinicopathological significance of golgi phosphoprotein 3 expression in papillary thyroid carcinoma. Zhonghua. Yi. Xue. Za. Zhi. 99:2831–2835 (2019). Liu, R., Cao, Z., Wu, M. Li, X., Fan, P., Liu, Z.: Golgi-apparatus genes related signature for predicting the progression-free interval of patients with papillary thyroid carcinoma. BMC Med. Genomics. 16(1):60 (2023). https://doi.org/10.1186/s12920-023-01485-z Topilko, A., Caillou, B.: Acetylcholinesterase and butyrylcholinesterase activities in human thyroid cancer cells. Cancer. 61:491–499 (1988). doi: 10.1002/1097-0142(19880201)61:33.0.CO;2-N . Saini, S., Sripada, L., Tulla, K., Qiao, G., Kunda, N., Maker, A.V., Prabhakar, B.S.: MADD silencing enhances anti-tumor activity of TRAIL in anaplastic thyroid cancer. Endocr. Relat. Cancer. 26(6):551–563 (2019). doi: 10.1530/ERC-18-0517 . Liu, J., Huang, Y., Li, T., Jiang, Z., Zeng, L., Hu, Z.: The role of the golgi apparatus in disease (review). Int. J. Mol. Med. 47:38 (2021). Pakdel, M., von Blume, J.: Exploring new routes for secretory protein export from the trans -Golgi network. Mol. Biol. Cell. 29, 235–240 (2018). doi: 10.1091/mbc.E17-02-0117 Polishchuk, E. V., Di Pentima, A., Luini, A., Polishchuk, R.S.: Mechanism of constitutive export from the Golgi: bulk flow via the formation, protrusion, and en bloc cleavage of large trans -Golgi network tubular domains. Mol. Biol. Cell. 14, 4470–4485 (2003). doi: 10.1091/mbc.e03-01-0033 Kulkarni-Gosavi, P., Makhoul, C., Gleeson, P.A.: Form and function of the golgi apparatus: scaffolds, cytoskeleton and signalling. FEBS Lett. 593:2289–2305 (2019). doi: 10.1002/1873-3468.13567 Rapoport, E.M., Ryzhov, I.M., Slivka, E.V., Korchagina, E.Y., Popova, I.S., Khaidukov, S.V., André, S., Kaltner, H., Gabius, H.J., Henry, S., Bovin, N.V.: Galectin-9 as a Potential Modulator of Lymphocyte Adhesion to Endothelium via Binding to Blood Group H Glycan. Biomolecules. 13(8):1166 (2023). doi: 10.3390/biom13081166 . Herzog, B.H., Fu, J., Xia, L.: Mucin-type O-glycosylation is critical for vascular integrity. Glycobiology. 24(12):1237–1241 (2014). doi: 10.1093/glycob/cwu058 . Kayili, H.M., Salih, B.: Site-specific N-glycosylation analysis of human thyroid thyroglobulin by mass spectrometry-based Glyco-analytical strategies. J. Proteomics. 267:104700 (2022). doi: 10.1016/j.jprot.2022.104700 . Conte, M., Arcaro, A., D'Angelo, D., Gnata, A., Mamone, G., Ferranti, P., Formisano, S., Gentile, F.: A single chondroitin 6-sulfate oligosaccharide unit at Ser-2730 of human thyroglobulin enhances hormone formation and limits proteolytic accessibility at the carboxyl terminus. Potential insights into thyroid homeostasis and autoimmunity. J. Biol. Chem. 281(31):22200–22211 (2006). doi: 10.1074/jbc.M513382200 . Antonelli, A., Ferrari, S.M., Corrado, A., Di Domenicantonio, A., Fallahi, P.: Autoimmune thyroid disorders. Autoimmun. Rev. 14(2):174–180 (2015). doi: 10.1016/j.autrev.2014.10.016 Ralli, M., Angeletti, D., Fiore, M., D’Aguanno, V., Lambiase, A., Artico, M., de Vincentiis, M., Greco, A.: Hashimoto’s thyroiditis: an update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation. Autoimmun. Rev. 19(10):102649 (2020). doi: 10.1016/j.autrev.2020.102649 Renkonen, J., Tynninen, O., Häyry, P., Paavonen, T., Renkonen, R.: Glycosylation might provide endothelial zip codes for organ-specific leukocyte traffic into inflammatory sites. Am. J. Pathol. 161(2):543–550 (2002). doi: 10.1016/S0002-9440(10)64210-1 . Trzos, S., Link-Lenczowski, P., Sokołowski, G., Pocheć, E.: Changes of IgG N-Glycosylation in Thyroid Autoimmunity: The Modulatory Effect of Methimazole in Graves' Disease and the Association With the Severity of Inflammation in Hashimoto's Thyroiditis. Front. Immunol. 13:841710 (2022). doi: 10.3389/fimmu.2022.841710 . Kuo, E.J., Thi, W.J., Zheng, F., Zanocco, K.A., Livhits, M.J., Yeh, M.W.: Individualizing Surgery in Papillary Thyroid Carcinoma Based on a Detailed Sonographic Assessment of Extrathyroidal Extension. Thyroid. 27(12):1544–1549 (2017). doi: 10.1089/thy.2017.0457 . Kaptan, E., Sancar-Bas, S., Sancakli, A., Bektas, S., Bolkent, S.: The effect of plant lectins on the survival and malignant behaviors of thyroid cancer cells. J. Cell. Biochem. 119(7):6274–6287 (2018). doi: 10.1002/jcb.26875 . Nozawa, Y., Ami, H., Suzuki, S., Tuchiya, A., Abe, R., Abe, M.: Distribution of sialic acid-dependent carbohydrate epitope in thyroid tumors: immunoreactivity of FB21 in paraffin-embedded tissue sections. Pathol. Int. 49(5):403–407 (1999). doi: 10.1046/j.1440-1827.1999.00884.x . Jones, M., Oswald, D., Joshi, S., Whiteheart, S., Orlando, R., Cobb, B.: B-Cell-Independent Sialylation of IgG. Proc. Natl. Acad. Sci. USA. 113(26):7207–7212 (2016). doi: 10.1073/pnas.1523968113 Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterialGLLIIv.08.05.24NAVC.doc Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4406005","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":303375793,"identity":"3bade612-ff6b-4e8c-a862-c5ce17f6b62a","order_by":0,"name":"Tania M. Cortázar","email":"","orcid":"","institution":"Universidad Nacional de Colombia. Bogotá","correspondingAuthor":false,"prefix":"","firstName":"Tania","middleName":"M.","lastName":"Cortázar","suffix":""},{"id":303375794,"identity":"1175163b-7ad2-4e81-ac0e-c8bddb64bc04","order_by":1,"name":"Nohora A. 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Bogotá","correspondingAuthor":false,"prefix":"","firstName":"Edgar","middleName":"A.","lastName":"Reyes-Montaño","suffix":""},{"id":303375796,"identity":"0a4b1f0c-121c-41e3-9582-a030dc57dc9e","order_by":3,"name":"Manuel A. Ballen-Vanegas","email":"","orcid":"","institution":"Universidad Nacional de Colombia. Bogotá","correspondingAuthor":false,"prefix":"","firstName":"Manuel","middleName":"A.","lastName":"Ballen-Vanegas","suffix":""},{"id":303375797,"identity":"53193c6a-7d27-4caf-ab71-23f6e58ec9c2","order_by":4,"name":"Jinneth Acosta","email":"","orcid":"","institution":"Universidad Nacional de Colombia. Bogotá","correspondingAuthor":false,"prefix":"","firstName":"Jinneth","middleName":"","lastName":"Acosta","suffix":""},{"id":303375798,"identity":"8341f642-f1a0-43c6-976d-67291828dc36","order_by":5,"name":"Orlando Ricuarte","email":"","orcid":"","institution":"Universidad Nacional de Colombia. Bogotá","correspondingAuthor":false,"prefix":"","firstName":"Orlando","middleName":"","lastName":"Ricuarte","suffix":""}],"badges":[],"createdAt":"2024-05-11 15:38:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4406005/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4406005/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":56934658,"identity":"382a8f57-bf8a-4aef-a813-cc4275ab7f17","added_by":"auto","created_at":"2024-05-22 10:38:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":129984,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChromatographic profiles, SDS-PAGE, and Western blotting of \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eGalactia lindenii\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e lectin II (GLL-II) obtained by DEAE anionic exchange and lactose-affinity chromatography.\u003c/strong\u003e a) DEAE profile: I (unretained) and II (retained and eluted) fractions monitored by optical density at 280 nm. b) Sepharose 4B-Lac profile. c) SDS-PAGE: Lanes 1 and 2: MW (kDa); lanes 4 and 5: Sepharose-Lac-RF containing the GLL-II subjected to 0.2 M of DTT and heating at 100 °C for 10 min (20 μg protein/lane). Lanes 6 and 7: Western blot for biotinylated GLL-II (6 μg).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4406005/v1/8f73e2e739755ba3ad321507.png"},{"id":56934661,"identity":"fd79669b-09bb-4966-b44c-b194ee6b7a95","added_by":"auto","created_at":"2024-05-22 10:38:38","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":766508,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGLL-II staining in classic Papillary Thyroid Carcinoma (PTC)\u003c/strong\u003e. Intense membrane labelling is identified in its apical portion and moderate granular in cytoplasm. a) 10x. b) 20x. c) 40 x\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4406005/v1/133ad624f4957dbc04f7b0e6.png"},{"id":56934662,"identity":"1a4198dd-3ac9-456a-bdcd-8dba5c783d28","added_by":"auto","created_at":"2024-05-22 10:38:38","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":779864,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGLL-II staining in thyroid non-neoplastic and PTC neoplastic tissues. \u003c/strong\u003eIntense apical membrane and moderate granular cytoplasm staining in PTC. Panel \u003cstrong\u003ea\u003c/strong\u003e also shows a non-neoplastic thyroid (arrow and area under the triangle) with intense granular cytoplasmic staining, but prominent apical membrane label is not evident. a) 4x, b) 10x, c) 20x, d) 40x.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4406005/v1/74d3c9b01c76b4205bbe0e51.png"},{"id":56934663,"identity":"e3559497-3ccd-4644-b46c-617c1bc6baa0","added_by":"auto","created_at":"2024-05-22 10:38:38","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":870221,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGLL-II staining in invasive encapsulated follicular variant papillary carcinoma (IEFV-PTC). \u003c/strong\u003eSpecific\u003cstrong\u003e \u003c/strong\u003emoderate and intense staining in the Golgi complex a.10x, b. 20x, c.40x.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4406005/v1/6710f8a6b64534f050a79ee3.png"},{"id":56934665,"identity":"c344f138-5756-41c6-8531-40093002ef5c","added_by":"auto","created_at":"2024-05-22 10:38:38","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":674466,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGLL-II staining in non-neoplastic thyroid with goiter changes.\u003c/strong\u003e Moderate cytoplasmic granular staining in follicular and C-cells, and non-uniform in colloid. Black arrows in (a) indicate staining of blood vessels and O-type RBCs. a) 20x, b) 40x, c) 20x.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-4406005/v1/8a414882fda62b5eab975692.png"},{"id":56934659,"identity":"2874c799-39c3-4509-b780-66a75ca1d88d","added_by":"auto","created_at":"2024-05-22 10:38:37","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":673099,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGLL-II staining patterns in Hashimoto's thyroiditis.\u003c/strong\u003e Staining in the lymphoid follicle germinal center, and in some cases, in follicular cell apical and granular cytoplasmic portion. a.10x, b. 20x, c. Negative control 10x.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-4406005/v1/9f271957a9e92350c6a736cb.png"},{"id":57781652,"identity":"e235a9a3-9b52-4adc-a28f-f794aeda5fa3","added_by":"auto","created_at":"2024-06-05 15:07:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4629387,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4406005/v1/83fb4bb1-a574-44c7-bb89-da32c78019c5.pdf"},{"id":56935088,"identity":"89c1265b-5e64-4d10-b468-00912a207561","added_by":"auto","created_at":"2024-05-22 10:46:37","extension":"doc","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":131072,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterialGLLIIv.08.05.24NAVC.doc","url":"https://assets-eu.researchsquare.com/files/rs-4406005/v1/5dddc4821f507577e1f1804e.doc"}],"financialInterests":"No competing interests reported.","formattedTitle":"Galactia lindenii lectin type-II. Proposal of its potential use in diagnostic tools","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLectins are proteins that possess carbohydrate recognition domains (CRD) through which they interact specifically and reversibly with structures in free carbohydrates or associated with proteins and lipids, and these interactions are fundamental in several biological activities [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The sequence of sugars and the glycosidic bond configurations contribute significantly to the affinity in the interaction between lectins and multivalent oligosaccharides in cellular glycoconjugates [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Glycotopes, three-dimensional epitopes represented by carbohydrates, are the minimal structural units confer maximum binding affinity to a specific glycan [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. These sugar epitopes occur at specific sites on glycoconjugates where they can be recognized by lectins or antibodies [\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11 CR12 CR13\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The glycotope concept has allowed an understanding of the contributions of individual structures in the glycan functions and biosynthetic pathways [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePlant lectins recognize their glycotopes playing a role in developmental and homeostatic functions; they can also recognize glycotopes in foreign organisms promoting symbiosis with nitrogen-fixing bacteria or engaging in defense mechanisms showing insecticidal, antifungal, or antimicrobial properties [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Lectins are used for various biomedical and agricultural applications due to their biotechnological potential and the increasingly detailed investigation of the binding specificity of their particular ligands [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Global glycosylation patterns are heterogeneous between glycoconjugates, cells, tissues, or body fluids, and at the same time are dependent on physiological conditions which allow the comparison of glycomic profiles in biological samples from patients under pathological and healthy states [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Current diagnosis platforms that include several plant lectins with different specificities (\u003cem\u003ee.g\u003c/em\u003e., lectin histochemistry, lectin blotting, lectin microarrays) have become valuable tools allowing the detection of glycosylation alterations and the determination of new glycotope biomarkers of healthy or pathological conditions [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe \u003cem\u003eGalactia lindenii\u003c/em\u003e plant is endemic to Colombia and belongs to the Diocleae tribu of the Fabaceae family [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The Diocleae type-I lectins are mainly mannose/glucose (Man/Glc)-specific, while Diocleae type-II lectins show affinity for determined galactosides depending on the lectin [\u003cspan additionalcitationids=\"CR31 CR32 CR33 CR34 CR35 CR36 CR37 CR38 CR39 CR40\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. In agreement with the above, the \u003cem\u003eG. lindenii\u003c/em\u003e seed contains the lectins GLL-I (mannose-specific) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]; and GLL-II which recognizes the trisaccharide that represents the histo-blood group H-type-II (Fucα1,2Galβ1,4GlcNAc-R), shows preference for O-glycans in comparison to N-glycans, and its binding activity is inhibited by the monosaccharide N-acetylgalactosamine (GalNAc) [\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe present study selected thyroid tissues from patients diagnosed previously with PTC, IEFV-PTC, HT, or non-neoplastic thyroid with goiter changes for histochemical evaluation using the lectin GLL-II. Besides, HA assays on RBCs of distinct glycomic profile were performed, complementing previous data. The results of all the above, along with a review of the glycoprofiles of other unhealthy conditions, indicate the potential utility of GLL-II as part of the lectin platforms used to discriminate human pathological samples from normal ones. The present work sheds light on the potential applications of GLL-II in diagnostic tools.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eMaterials\u003c/h2\u003e \u003cp\u003e \u003cem\u003eGalactia lindenii\u003c/em\u003e seeds collected in F\u0026uacute;quene, Cundinamarca (Colombia) were botanically identified at the Natural Sciences Institute (vouchers COL 15115 and COL 580116) from Universidad Nacional de Colombia (UNAL). Paraffin-embedded tissue specimens block of tissues from patients diagnosed previously with PTC, IEFV-PTC, HT, or non-neoplastic thyroid with goiter changes, were selected from the UNAL Pathology Department Tissue Bank at the Medicine Faculty. Fresh human and sheep blood samples were obtained from the UNAL Clinical Laboratory and Veterinary Faculty\u0026rsquo;s Hematology Laboratory. Pharmacia and Bio-Rad equipment was used for ion exchange and affinity chromatographies. Sepharose-4B, DEAE-Sephacel, NaCl, protein standards, \u003cem\u003eClostridium perfringens\u003c/em\u003e α-sialidase, bovine liver β-galactosidase, streptavidin and peroxidase were obtained from Sigma-Aldrich. N-hydroxysuccinimide (NHS) ester of biotin (sulfobiotin-X-NHS) was purchased from Calbiochem. The reagents were all analytical grade.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eExtraction and Purification of GLL-II\u003c/h2\u003e \u003cp\u003eThe purification of GLL-II was carried out as previously described [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The Sepharose-Lactose (Sepharose-Lac) matrix was prepared by coupling ethanol-washed lactose to divinyl sulphone-activated Sepharose 4B [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Buffer changes and protein concentration were performed by ultrafiltration using a 10 kDa MW cut-off cellulose membrane (Millipore, PLG CO6210; Amicon Bioseparations, USA). Protein content was determined by the bicinchoninic acid (BCA) assay [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. GLL-II purification steps were evaluated by SDS-PAGE electrophoresis according to Laemmli [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e], and the hemagglutinating activity in each step of lectin purification was determined.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eHemagglutinating activity (HA)\u003c/h2\u003e \u003cp\u003eThe HA was assayed by serial lectin dilutions in phosphate buffer saline (PBS, pH 7.2) on microtiter plates using RBC suspensions [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. The erythrocytes exposing the Thomsen-Friedenreich (TF) and Thomsen-nouveau (Tn) glycotopes were prepared from suspensions of human type-A RBCs subjected to enzymatic treatment using α-sialidase, or sequentially α-sialidase and β-galactosidase, respectively, following the methodologies described [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. The minimum agglutinating concentration (MAC) represents the lowest tested concentration in a serial dilution of lectin at which cell agglutination was visible.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eTissue specimens\u003c/h2\u003e \u003cp\u003eA block of 21 formalin-fixed paraffin-embedded tissue specimens from patients diagnosed previously with thyroid disorders were selected from the Tissue Bank. Two observers determined the labeling location and percentage of reactive cells on neoplastic and non-neoplastic thyroid tissues. Labeling intensity was assessed using a semiquantitative scale: slight +, moderate ++, and intense +++ (Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eLectin histochemistry\u003c/h2\u003e \u003cp\u003eGLL-II lectin was coupled to biotin following a methodology modified by Wu et al [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e], using two successive additions of sulfobiotin-X-NHS (2:1 w/w, 12 h interval). A streptavidin-peroxidase conjugate (SP) was obtained by coupling 1 mg streptavidin to 5 mg peroxidase as described [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Tissue sections were deparaffinized over 12 h at 60 ˚C, hydrated with xylol, and subjected to differential treatment with ethanol (absolute, 96%, and 70%) for 4 min each. The subsequent steps were performed at room temperature. Tissues were cleared with Triton X-100 at 0.1% in PBS for 30 min. An additional recovery step was then taken in a citrate-phosphate buffer, pH 6, for 20 min followed by three washes with PBS-Tween (0.1%) for 5 min. Endogenous peroxidase was inactivated using 0.3% hydrogen peroxide and 10% methanol solution over 30 min. The slices were washed with PBS-Tween and incubated with 200 \u0026micro;l fetal bovine serum (FBS, 10%) for 30 min. Then, the blocking solution was discarded, and the slices were incubated with 10 \u0026micro;g/mL of biotinylated GLL-II in 10% PBS-FBS over 30 min. Next, the tissues were washed with PBS-Tween, incubated with SP (1:1000) in PBS-FBS over 1 h, and developed with 1% 3,3\u0026rsquo;-diaminobenzidine (DAB) tetrahydrochloride solution (Dako 3468 kit) in Tris-HCl 50 mM, pH 7.3, and 5 \u0026micro;l of H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e at 30% /10 mL of solution. Harris hematoxylin stain was used for contrast. Negative controls were processed simultaneously. Progressive dehydration was done with 70, 90, and 96% ethanol for 4 min each. Finally, the slices were mounted on slides with cytoresin and read.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results and discussion","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eGLL-II purification and coupling to biotin\u003c/h2\u003e \u003cp\u003eThe \u003cem\u003eG. lindenii\u003c/em\u003e seed extracts were fractioned on diethylaminoethyl cellulose (DEAE)-Sephacel support equilibrated in PBS (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). This anion exchange chromatography allows GLL-II to be separated from other proteins including the other lectin present in the seeds. GLL-II is in the DEAE-unretained fraction (DEAE-URF: profile fraction I) considering its basic isoelectric point (pI)\u0026thinsp;~\u0026thinsp;8.3, [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], while GLL-I (pI: 6.15) is in the DEAE-retained fraction (DEAE-RF: profile fraction II) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. DEAE-URF was fractionated on Sepharose-Lac supports. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb presents a Lac-affinity chromatographic profile wherein the GLL-II activity is found in the Sepharose-Lac retained fraction (Sepharose-Lac-RF: profile fraction II) eluted with 0.2 M lactose in PBS. No lectin activity has been detected for Sepharose-Lac-URF. SDS-PAGE for Sepharose-Lac-RF consistently revealed the 24 kDa band as being the principal constituent corresponding to the GLL-II monomer (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec, lanes 4 and 5). A band\u0026thinsp;~\u0026thinsp;50 kDa can sometimes be observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec) corresponding to the lectin dimer due to incomplete tetramer dissociation, concurring with previous reports [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Biotin-conjugated GLL-II agglutinated O-type RBCs at a minimum concentration of 1.4 \u0026micro;g/mL (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), indicating the lectin activity was preserved after the coupling process. Using Dot-blot, the biotinylated lectin could still be detected with quantities below 0.2 \u0026micro;g (not shown). In Western blot assays, the biotin-conjugated GLL-II subjected to denaturation and heating showed bands of 24 kDa or 50 kDa (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec, lanes 6 and 7). The biotinylated lectin was used in the histochemical assays.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStages of Galactia lindenii lectin II (GLL-II) purification and coupling to biotin\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSteps\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVol\u003c/p\u003e \u003cp\u003e(mL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProtein concentration\u003c/p\u003e \u003cp\u003e(mg/mL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003eprotein\u003c/p\u003e \u003cp\u003e(mg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTitle\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMAC\u003c/p\u003e \u003cp\u003e(\u0026micro;g/mL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePurification fold\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePool of extracts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1080\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1:256\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDEAE-URF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e510\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1:2048\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSepharose-Lac-RF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1:2048\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiotinylated GLL-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1:2048\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMAC: minimum agglutinating concentration on O\u003csup\u003e+\u003c/sup\u003e RBCs (100 \u0026micro;l of protein solution). URF: unretained fraction, RF: retained fraction.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eHemagglutinating activity on erythrocytes of different glycomic profile\u003c/h2\u003e \u003cp\u003eThe HA was evaluated with serial dilutions of pure GLL-II on erythrocytes (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), complementing previous results with different human and animal RBCs (Table S2). HA approach allows testing multivalent oligosaccharide ligands in the context of a cellular surface environment [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e] and evaluating broad specificities of the lectins [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] since each RBC type exposes determined predominant glycans [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR51 CR52 CR53 CR54 CR55 CR56\" citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. The histo-blood groups and related antigens are non-reducing terminal elements of the oligosaccharide chains in glycolipids and glycoproteins expressed on RBCs, as well as, in epithelial and endothelial cells [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan additionalcitationids=\"CR59 CR60 CR61 CR62\" citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e]. These terminal carbohydrate structures are particularly relevant in medicine because the change in their expression level alters the cell\u0026acute;s phenotype and can serve as markers of unhealthy states [\u003cspan additionalcitationids=\"CR65 CR66 CR67 CR68\" citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e]. Some human glycotopes are listed in the cluster of differentiation (CD) nomenclature for classifying cell surface antigens [\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e]. The predominant glycotopes exposed in the RBCs tested in the present study are described in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e using the textual structural representations proposed by the Consortium for Functional Glycomics (CFG) [\u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e] and indicating the CD number where applicable.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMinimum hemagglutinating concentration (MAC) of GLL-II lectin on different erythrocyte types\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eErythrocyte type\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMAC (\u0026micro;g/mL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePredominant glycotope\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGlycotope textual structural nomenclature \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eO *\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH-type-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFucα1,2Galβ1,4GlcNAc-R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCD173\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTF\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThomsen-Friedenreich\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGalβ1,3GalNAcα1-O-S\u0026frasl;T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCD176\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTn\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGalNAcα1-O-S\u0026frasl;T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCD175\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSheep\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eForssman\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGalNAcα1,3GalNAcβ-R-Cer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e* No difference between Rh\u0026thinsp;+\u0026thinsp;and Rh-. \u003csup\u003ea\u003c/sup\u003e Proposed by the CFG [\u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e]. Cer: ceramide. CD: cluster of differentiation [\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e]. Fuc: fucose. Gal: galactose. GalNAc: N-acetylgalactosamine. GlcNAc: N-acetylglucosamine. NA: no agglutination. R: N/O-glycan or glycolipid remaining part. S/T: serine/threonine. α/β: glycosidic bond configuration. For the agglutination assays, the pure lectin was used (Sepharose-Lac-RF fraction).\u003c/p\u003e \u003cp\u003eThe HA results corroborated the GLL-II marked preference for human O type RBCs (MAC: 1.2 \u0026micro;g/mL) among all types of human and non-human RBCs evaluated so far (Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and S2), which correlates with the predominance of the H-type-II glycotope expression in the human O type erythrocyte glycoconjugates (\u0026asymp;\u0026thinsp;2.0 x 10\u003csup\u003e6\u003c/sup\u003e sites/erythrocyte) [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. The higher specificity of GLL-II towards the H-type-II glycotope, compared to other glycoforms, has also been observed previously in Enzyme-Linked Lectinosorbent (ELLSA) and lectin inhibition assays [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. On the other hand, here it was probed the agglutinating activity of GLL-II on TF- and Tn-RBCs, which were agglutinated by GLL-II with the second (2.1 \u0026micro;g/mL) and the third (4.3 \u0026micro;g/mL) minimum MACs, respectively, after that of the O type RBCs (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The last agreed with the interactions between GLL-II with free O-glycoforms exhibiting the TF- or Tn-glycotopes, as observed in Dot-blot (DB) assays [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. All \u003cem\u003ein vitro\u003c/em\u003e tests together indicate that the GLL-II ligands, in order of interaction, are the H-type-II\u0026thinsp;\u0026gt;\u0026thinsp;TF\u0026thinsp;\u0026gt;\u0026thinsp;Tn glycotopes (Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and S2). The above results are relevant because those three glycotopes have are unregulated in some unhealthy conditions, as indicated later in the text.\u003c/p\u003e \u003cp\u003eWe also confirmed the lack of GLL-II activity on sheep RBCs (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), whose predominant glycotope is the Forssman antigen [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. It is noteworthy that despite GLL-II interacting with RBCs and glycoforms exposing the α-GalNAc monosaccharide (Tn) or the Galβ1,3GalNAcα disaccharide (TF), its interaction with oligosaccharides that present α/β-GalNAc or α/βGal in the terminal position is very weak or absent, as is the case of Forssman, LacDiNAc, Galili, and A/B group oligosaccharides [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Furthermore, GLL-II does not agglutinate canine, murine, equine or cattle RBCs using concentrations up to 1.4 mg/mL of the lectin [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]; in those RBCs predominate glycans and gangliosides exposing different types of sialic acids (Neu5Ac; Neu5,9Ac2; or Neu5Gc) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR53 CR54 CR55 CR56\" citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. Similarly, GLL-II did not interact with glycoproteins exposing N/O-glycans carrying terminal Neu5Ac [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePotential uses of GLL-II lectin in diagnostic tools\u003c/h2\u003e \u003cp\u003eGlycosylation is a complex post-translational modification involved in critical biological processes, such as protein folding and stability, cell growth, and cellular interactions [\u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e]. In humans, an altered protein and lipid glycosylation is a hallmark of cancer [\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e]. It can impact all steps in tumor progression and immune evasion due to their effects on cell-cell and cell-extracellular matrix (ECM) interactions, cell growth, apoptosis, and cell death [\u003cspan additionalcitationids=\"CR75\" citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e]. In the diagnosis platforms based on glycosylation changes, the commercial lectins UEA-I from \u003cem\u003eUlex europaeus\u003c/em\u003e seeds and TJA-II from \u003cem\u003eTrichosanthes japonica\u003c/em\u003e root tubers, which can recognize the fucosylated trisaccharide H-type-II (Fucα1,2Galβ1,4GlcNAc-R), have usually been included [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e]. The results obtained so far show that GLL-II presents less tolerance to substitutions on the moieties that make up the trisaccharide, compared to UEA-I and TJA-II; furthermore, although the three lectins share some ligands, each of them also has different additional ligands (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). So, we propose the inclusion of GLL-II in the lectin platforms to complement the results that can be obtained with UEA-I and TJA-II as described above.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDifferences between GLL-II and commercial lectins that can recognize the glycotope H-type-II\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLectin\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePredominant\u003c/p\u003e \u003cp\u003eligand(s)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAdditional ligands\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTerminal\u003c/p\u003e \u003cp\u003eα1,2-Fuc\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eSubstitutions\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMono-saccharide inhibitor\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eon βGal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eon GlcNAc\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGLL-II\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eH-type-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2'-FL,\u003c/p\u003e \u003cp\u003eTF, Tn,\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIncreases interaction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDoes not tolerate\u003c/p\u003e \u003cp\u003eα2,3/6-NeuAc/NeuGc or\u003c/p\u003e \u003cp\u003eα1,3-Gal (as in Galili)\u003c/p\u003e\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDoes not tolerate\u003c/p\u003e \u003cp\u003eα1,3-Fuc (as in Le\u003csup\u003eY\u003c/sup\u003e),\u003c/p\u003e \u003cp\u003eβ1,3-Gal\u0026thinsp;+\u0026thinsp;α1,4-Fuc\u003c/p\u003e \u003cp\u003e(as in Le\u003csup\u003eA\u003c/sup\u003e) or\u003c/p\u003e\u003cp\u003eα2,6-NeuAc/NeuGc.\u003c/p\u003e\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGalNAc\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUEA-I\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eH-type-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2'-FL,\u003c/p\u003e \u003cp\u003esulfated 2'-FL, Le\u003csup\u003eY\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIncreases interaction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDoes not tolerate\u003c/p\u003e \u003cp\u003eα2,3/6-NeuAc.\u003c/p\u003e \u003cp\u003eTolerates sulfation at C6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTolerates α1,3-Fuc\u003c/p\u003e \u003cp\u003eor 6-O-sulfation.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eL-Fuc\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTJA-II\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eH-type III,\u003c/p\u003e \u003cp\u003eH-type-IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH-type-II,\u003c/p\u003e \u003cp\u003e2'-FL, Sd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIncreases interaction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDoes not tolerate\u003c/p\u003e \u003cp\u003eα2,3/6-NeuAc or\u003c/p\u003e \u003cp\u003eα1,3-GalNAc.\u003c/p\u003e\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDoes not tolerate\u003c/p\u003e \u003cp\u003eα1,3/4-Fuc.\u003c/p\u003e \u003cp\u003eTolerates α2,6-NeuAc.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGalNAc\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eData: GLL-II [30, 32 and present work]; UEA-I [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e, \u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e79\u003c/span\u003e]; TJA-II [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR80\" class=\"CitationRef\"\u003e80\u003c/span\u003e]. Galilli antigen (α-gal glycotope): Galα1,3Galβ1,4GlcNAc-R. Glc: glucose. Le\u003csup\u003eA\u003c/sup\u003e: Lewis A antigen, Galβ1,3(Fucα1,4)GlcNAcβ-R.. Le\u003csup\u003eY\u003c/sup\u003e: Lewis Y antigen, Fucα1,2Galβ1,4(Fucα1,3)GlcNAc-R. Neu5Gc: N-glycolylneuraminic acid. Sd antigen: GalNAcβl,4Galβl-R. 2'-FL: 2\u0026rsquo;fucosyllactose, Fucα1,2Galβ1,4Glc-R. Sulfonated forms of 2'-FL: Fucα1,2Galβ1,4(SO\u003csub\u003e3\u0026minus;\u003c/sub\u003eα6)O-Glc-R and Fucα1,2(SO\u003csub\u003e3\u003c/sub\u003e)Galβ1,4Glc-R. Other nomenclature and glycosidic bond configurations as in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eThe UEA-I lectin recognizes structures with exposed terminal fucose (Fuc); its predominant ligand is the H-type-II glycotope (Ka: 4,3 x 10\u003csup\u003e4\u003c/sup\u003e M\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e; Kd: 8.1 \u0026micro;M, Isothermal Titration Calorimetry, ITC), and it also interacts with the 2'-fucosyllactose (2\u0026rsquo;-FL; Kd: 12.5 \u0026micro;M, ITC), Lewis Y antigen [Le\u003csup\u003eY\u003c/sup\u003e (CD174); Kd: 19.8 \u0026micro;M; ITC], and sulfonated 2\u0026rsquo;-FL forms. UEA-I interactions are mainly centered on the fucose residues of its ligands (α1,2-Fuc or α1,3-Fuc), whereas it is less sensitive to substitutions in galactose (Gal) and N-acetylglucosamine (GlcNAc) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e, \u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e79\u003c/span\u003e]. For its part, the TJA-II lectin preferably recognizes oligosaccharides exposing the H-type-III and H-type-IV glycotopes (Fucα1,2Galβ1,3GalNacα/β), which present terminal α1,2-Fuc followed by Gal and GlcNAc linked in a β1,3 bond, as is the case of the Lacto-N-Fucopentose-I (LNFP-I, Ka: 3,05 x 10\u003csup\u003e5\u003c/sup\u003e M\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, equilibrium dialysis), whereas for this lectin the H-type-II is an additional ligand [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR80\" class=\"CitationRef\"\u003e80\u003c/span\u003e]. Last, according to our \u003cem\u003ein vitro\u003c/em\u003e results carried out so far, the GLL-II lectin predominant ligand is the H-type-II glycotope; the interactions with the three moieties within the trisaccharide are relevant since the absence of α1,2-Fuc or GlcNAc, as well as substitutions in β-Gal or GlcNAc avoid the recognition (Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). GLL-II prefers oligosaccharides with terminal α1,2-Fuc followed by Gal and GlcNAc linked in a β1,4 bond. It also interacts with the 2-FL (Ka: 1 x 10\u003csup\u003e5\u003c/sup\u003e M\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, Kd: 9,7 \u0026micro;M, by Frontal Affinity Chromatography, FAC; Vega \u003cem\u003eet al\u003c/em\u003e, unpublished), and among the non-fucosylated oligosaccharides, its additional ligands are the TF and Tn glycotopes (Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and S2). GLL-II and TJA-II do not interact with the difucosylated Le\u003csup\u003eY\u003c/sup\u003e antigen (α1,2/3-Fuc) [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR80\" class=\"CitationRef\"\u003e80\u003c/span\u003e]. The differences on the fine sugar-binding specificity of the three H-type-II-recognizing lectins will depend on the structure, shape, and size of the carbohydrate-binding sites on the lectin CRD, leading to a great diversity in their sugar-recognition capacity.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eHistochemical evaluation of thyroid disorders using the GLL-II lectin\u003c/h2\u003e \u003cp\u003eThyroid cancer is a common endocrine-related malignant tumor with a global increased incidence in recent years [\u003cspan citationid=\"CR81\" class=\"CitationRef\"\u003e81\u003c/span\u003e, \u003cspan citationid=\"CR82\" class=\"CitationRef\"\u003e82\u003c/span\u003e]. The 5th edition of the WHO classification of endocrine tumors released in 2022 integrates the tumor morphological characteristics and the oncogene-driven signaling pathways that have an impact on the intracellular metabolism (\u003cem\u003eBRAF\u003c/em\u003e-like or \u003cem\u003eRAS\u003c/em\u003e-like) [\u003cspan citationid=\"CR83\" class=\"CitationRef\"\u003e83\u003c/span\u003e, \u003cspan citationid=\"CR84\" class=\"CitationRef\"\u003e84\u003c/span\u003e], thus categorizing the follicular-derived thyroid tumors into three groups: 1) Benign tumors represented by follicular nodular disease, follicular adenoma, follicular adenoma with papillary architecture, and oncocytic adenoma; 2) Low risk-neoplasms including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), hyalinizing trabecular tumors, and well-differentiated tumor of uncertain malignant potential (WDT-UMP); and 3) Malignant neoplasms which include papillary thyroid (PTC), follicular thyroid (FTC), oncocytic thyroid (OCA), invasive encapsulated follicular variant papillary thyroid (IEFV-PTC), poorly differentiated thyroid (PDTC), differentiated high-grade thyroid (DHGTC), and anaplastic thyroid (ATC) carcinomas [\u003cspan citationid=\"CR83\" class=\"CitationRef\"\u003e83\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGlycosylation is altered in thyroid cancer showing differences in expression level of glycoforms when compared to healthy controls, and in turn, between the distinct TC tumor types [\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e, \u003cspan additionalcitationids=\"CR86 CR87 CR88 CR89\" citationid=\"CR85\" class=\"CitationRef\"\u003e85\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR90\" class=\"CitationRef\"\u003e90\u003c/span\u003e]. Those changes have been seen mainly in fucosylation, sialylation, O-GlcNAcylation, O-GalNAc extension grade [\u003cspan additionalcitationids=\"CR91\" citationid=\"CR90\" class=\"CitationRef\"\u003e90\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR92\" class=\"CitationRef\"\u003e92\u003c/span\u003e], and glycoconjugate complexity [\u003cspan citationid=\"CR85\" class=\"CitationRef\"\u003e85\u003c/span\u003e, \u003cspan citationid=\"CR87\" class=\"CitationRef\"\u003e87\u003c/span\u003e]. Research in glycobiology and endocrinology point out that oligosaccharides are critically involved in the thyroid functioning and that changes in glycosylation profiles lead to thyroid pathologies, including thyroid carcinogenesis and autoimmunity [\u003cspan citationid=\"CR90\" class=\"CitationRef\"\u003e90\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the present study, tissues from patients diagnosed previously with PTC, IEFV-PTC, HT, or non-neoplastic thyroid with goiter changes, were selected for histochemical evaluation using the biotinylated GLL-II on the different thyroid tissue samples (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). A summary of all the evaluated cases, in normal and tumor tissues, is presented in the Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e. In normal tissue a non-uniform cytoplasmic granular staining was observed in thyroid follicular cells and colloid (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea), in contrast to samples of distinct thyroid disorders which showed additional or different label intensity and/or distribution (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e) indicating a site-specific presence of GLL-II ligands in different states of the thyroid gland as described below.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePapillary thyroid carcinoma (PTC)\u003c/h2\u003e \u003cp\u003ePTC is the most frequent form of thyroid cancer. It occurs predominantly in middle-aged adults with a 3:1 female-to-male ratio, and the known risk factors for PTC include exposure to significant ionizing radiation, high dietary iodine, obesity, and genetic syndromes [\u003cspan citationid=\"CR93\" class=\"CitationRef\"\u003e93\u003c/span\u003e]. In PTC tissues, the GLL-II labeling showed an intense follicular cell apical surface staining together with a moderate cytoplasmic granular label in between 40% and 100% of the cells (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e), while non-neoplastic tissue presented cytoplasmic non-uniform and granular staining in follicular cells and colloid without evident particular membrane label (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). The marked GLL-II membrane pattern indicates that the apical surface of PTC follicular cells contains a high amount of receptors for the lectin, and coincides with previous observations where using lectins, monoclonal antibodies (mAbs), and glycosidases, it has been detected a significantly increased expression of fucosylated glycotopes, including the H-type-II [\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e, \u003cspan citationid=\"CR85\" class=\"CitationRef\"\u003e85\u003c/span\u003e, \u003cspan additionalcitationids=\"CR96 CR97 CR98 CR99 CR100\" citationid=\"CR95\" class=\"CitationRef\"\u003e95\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR101\" class=\"CitationRef\"\u003e101\u003c/span\u003e], as well as the O-glycan TF [\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e, \u003cspan citationid=\"CR91\" class=\"CitationRef\"\u003e91\u003c/span\u003e, \u003cspan citationid=\"CR98\" class=\"CitationRef\"\u003e98\u003c/span\u003e, \u003cspan additionalcitationids=\"CR103\" citationid=\"CR102\" class=\"CitationRef\"\u003e102\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR104\" class=\"CitationRef\"\u003e104\u003c/span\u003e] in human PTC. Additionally, in the same samples (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), Harris hematoxylin allowed observing the typical appearance of the enlarged, elongated and overlapping nuclei presenting irregular contours, few mitotic figures, and a pale aspect due to finely textured, evenly distributed chromatin in PTC [\u003cspan citationid=\"CR93\" class=\"CitationRef\"\u003e93\u003c/span\u003e, \u003cspan citationid=\"CR94\" class=\"CitationRef\"\u003e94\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eH-type-II glycotope\u003c/em\u003e Fucosylation is altered in inflamed and cancer tissues [\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e, \u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e, \u003cspan citationid=\"CR90\" class=\"CitationRef\"\u003e90\u003c/span\u003e]. Glycoconjugates containing α-Fuc participate in diverse interactions between cells and ECM [\u003cspan additionalcitationids=\"CR106\" citationid=\"CR105\" class=\"CitationRef\"\u003e105\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR107\" class=\"CitationRef\"\u003e107\u003c/span\u003e], and the change in their expression correlates with tumor growth, invasion, and metastasis [\u003cspan citationid=\"CR95\" class=\"CitationRef\"\u003e95\u003c/span\u003e, \u003cspan additionalcitationids=\"CR108 CR109 CR110 CR111 CR112\" citationid=\"CR107\" class=\"CitationRef\"\u003e107\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR113\" class=\"CitationRef\"\u003e113\u003c/span\u003e]. The aberrant fucosylation is mainly attributed to upregulation of fucosyltransferases (FUTs) and downregulation of α-L-fucosidases (FUCAs), promoting inflammatory conditions and malignancy [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR105\" class=\"CitationRef\"\u003e105\u003c/span\u003e, \u003cspan citationid=\"CR108\" class=\"CitationRef\"\u003e108\u003c/span\u003e, \u003cspan additionalcitationids=\"CR114\" citationid=\"CR113\" class=\"CitationRef\"\u003e113\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR115\" class=\"CitationRef\"\u003e115\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn particular, the increase of the fucosylated H-type-II glycotope is related to the overexpression of FUT1 and FUT2 that catalyze the transfer of Fuc through an α1,2 link to a terminal Gal in O/N-glycans or lipids [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR116\" class=\"CitationRef\"\u003e116\u003c/span\u003e], leading to the increase of α1,2-fucosylated glycans during the tumor progression in a variety of tissues [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR100\" class=\"CitationRef\"\u003e100\u003c/span\u003e, \u003cspan citationid=\"CR110\" class=\"CitationRef\"\u003e110\u003c/span\u003e, \u003cspan citationid=\"CR114\" class=\"CitationRef\"\u003e114\u003c/span\u003e, \u003cspan citationid=\"CR116\" class=\"CitationRef\"\u003e116\u003c/span\u003e, \u003cspan citationid=\"CR117\" class=\"CitationRef\"\u003e117\u003c/span\u003e]. Upregulated FUT1 promotes cancer cell proliferation [\u003cspan citationid=\"CR107\" class=\"CitationRef\"\u003e107\u003c/span\u003e, \u003cspan citationid=\"CR118\" class=\"CitationRef\"\u003e118\u003c/span\u003e], and the increase in both FUT1 and FUT2 induces a decrease in cadherin expression, leading to a reduced cellular adhesiveness, a defining feature of cancer [\u003cspan citationid=\"CR116\" class=\"CitationRef\"\u003e116\u003c/span\u003e, \u003cspan citationid=\"CR119\" class=\"CitationRef\"\u003e119\u003c/span\u003e]. The glycoprotein that represents the prostate antigen/kallikrein 3 (PSA/KLK3), the fucosylated GM1 ganglioside (FucGM1) in lung SCC carcinoma [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], and the globo-H glycosphingolipid in breast cancer [\u003cspan citationid=\"CR116\" class=\"CitationRef\"\u003e116\u003c/span\u003e], are α1,2-fucosylated. In they turn, the PTC carcinoma glycoconjugates decorated with α1,2-Fuc in their non-reducing termini carry the following glycotopes: a) H-type-II determined by using GLL-II (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), UEA-I [\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e], and mAbs [\u003cspan citationid=\"CR95\" class=\"CitationRef\"\u003e95\u003c/span\u003e, \u003cspan citationid=\"CR98\" class=\"CitationRef\"\u003e98\u003c/span\u003e, \u003cspan citationid=\"CR101\" class=\"CitationRef\"\u003e101\u003c/span\u003e, \u003cspan citationid=\"CR120\" class=\"CitationRef\"\u003e120\u003c/span\u003e], b) Le\u003csup\u003eY\u003c/sup\u003e recognized by UEA-I and mAbs [\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e, \u003cspan citationid=\"CR95\" class=\"CitationRef\"\u003e95\u003c/span\u003e, \u003cspan citationid=\"CR98\" class=\"CitationRef\"\u003e98\u003c/span\u003e, \u003cspan citationid=\"CR101\" class=\"CitationRef\"\u003e101\u003c/span\u003e], c) Le\u003csup\u003eB\u003c/sup\u003e detected with mAbs [\u003cspan citationid=\"CR98\" class=\"CitationRef\"\u003e98\u003c/span\u003e, \u003cspan citationid=\"CR101\" class=\"CitationRef\"\u003e101\u003c/span\u003e] (this Lewis antigen contains α1,2-Fuc and also α1,4-Fuc), and d) Globo-H ceramide recognized in tissue microarrays [\u003cspan citationid=\"CR123\" class=\"CitationRef\"\u003e123\u003c/span\u003e]. In thyroid cancer, the H-type-II glycotope has been more readily and frequently detected in PTC compared to follicular adenomas, FTC and ATC [\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e, \u003cspan citationid=\"CR95\" class=\"CitationRef\"\u003e95\u003c/span\u003e, \u003cspan citationid=\"CR97\" class=\"CitationRef\"\u003e97\u003c/span\u003e, \u003cspan citationid=\"CR98\" class=\"CitationRef\"\u003e98\u003c/span\u003e, \u003cspan citationid=\"CR101\" class=\"CitationRef\"\u003e101\u003c/span\u003e, \u003cspan citationid=\"CR120\" class=\"CitationRef\"\u003e120\u003c/span\u003e, \u003cspan citationid=\"CR121\" class=\"CitationRef\"\u003e121\u003c/span\u003e]; meanwhile, it also has been found in the non-acid glycosphingolipid fraction isolated from human neuroendocrine medullary thyroid carcinoma (MTC), as determined by mass spectrometry [\u003cspan citationid=\"CR112\" class=\"CitationRef\"\u003e112\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNeoexpression of poly-N-acetyllactosamine structures (poly-LacNAc) is another motif related to the presence of the H-type-II in PTC since poly-LacNAc are direct precursors of that glycotope in cancer cells [\u003cspan citationid=\"CR96\" class=\"CitationRef\"\u003e96\u003c/span\u003e]. Short and long linear unbranched-, and highly branched poly-LacNAc sequences, have been detected in PTC, while lectins specific to the distinct types of poly-LacNAc exhibited slight or no reactivity with the cells in follicular adenomas and FTC [\u003cspan citationid=\"CR96\" class=\"CitationRef\"\u003e96\u003c/span\u003e, \u003cspan citationid=\"CR97\" class=\"CitationRef\"\u003e97\u003c/span\u003e, \u003cspan citationid=\"CR124\" class=\"CitationRef\"\u003e124\u003c/span\u003e]. Last, although normal adult thyroid follicular cells do not express the ABH histo-blood antigens [\u003cspan additionalcitationids=\"CR96\" citationid=\"CR95\" class=\"CitationRef\"\u003e95\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR97\" class=\"CitationRef\"\u003e97\u003c/span\u003e, \u003cspan citationid=\"CR120\" class=\"CitationRef\"\u003e120\u003c/span\u003e, \u003cspan citationid=\"CR125\" class=\"CitationRef\"\u003e125\u003c/span\u003e], and the clinical and pathological features did not differ according the ABH blood group of the PTC patient [\u003cspan citationid=\"CR126\" class=\"CitationRef\"\u003e126\u003c/span\u003e], the reappearance of the H-type-II glycotope had shown a correlation with a loss of A or B antigens during metastases due probably to the lack of A- and B-glycosyltransferase activities [\u003cspan citationid=\"CR95\" class=\"CitationRef\"\u003e95\u003c/span\u003e, \u003cspan citationid=\"CR101\" class=\"CitationRef\"\u003e101\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOther types of fucosylation also are increased in PTC compared to normal thyroid. That is how the α1,6-Fuc core (FUT8) is a factor related with PTC tumor size and lymph node metastasis [\u003cspan citationid=\"CR99\" class=\"CitationRef\"\u003e99\u003c/span\u003e]. Furthermore, in addition to Le\u003csup\u003eY\u003c/sup\u003e and Le\u003csup\u003eB\u003c/sup\u003e, the PTC carcinomas also show stronger immunoreactivity to other fucosylated or sialofucosylated forms of Lewis antigens (Le\u003csup\u003eA\u003c/sup\u003e, Le\u003csup\u003eX\u003c/sup\u003e, sLe\u003csup\u003eA\u003c/sup\u003e and sLe\u003csup\u003eX\u003c/sup\u003e) [\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e, \u003cspan additionalcitationids=\"CR97 CR98 CR99 CR100\" citationid=\"CR96\" class=\"CitationRef\"\u003e96\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR101\" class=\"CitationRef\"\u003e101\u003c/span\u003e, \u003cspan citationid=\"CR120\" class=\"CitationRef\"\u003e120\u003c/span\u003e, \u003cspan citationid=\"CR121\" class=\"CitationRef\"\u003e121\u003c/span\u003e], which carry α1,3-Fuc or α1,4-Fuc added on GlcNAc by FUT3-FUT7 or FUT9 [\u003cspan citationid=\"CR127\" class=\"CitationRef\"\u003e127\u003c/span\u003e]. The ectopic expression of sLe\u003csup\u003eA\u003c/sup\u003e and sLe\u003csup\u003eX\u003c/sup\u003e (normally expressed by leukocytes) by several cancers is associated with malignancy [\u003cspan citationid=\"CR113\" class=\"CitationRef\"\u003e113\u003c/span\u003e]. The number of Lewis positive cases has been higher in PTC than in FTC carcinomas [\u003cspan citationid=\"CR98\" class=\"CitationRef\"\u003e98\u003c/span\u003e, \u003cspan citationid=\"CR120\" class=\"CitationRef\"\u003e120\u003c/span\u003e, \u003cspan citationid=\"CR121\" class=\"CitationRef\"\u003e121\u003c/span\u003e]. However, the α1,3-fucosylation (FUT7) of sialylated glycans in the EGFR receptor promotes tumor-cell proliferation and migration in FTC [\u003cspan citationid=\"CR128\" class=\"CitationRef\"\u003e128\u003c/span\u003e]. In other ways, the downregulation of FUCAs involved in the hydrolysis of terminal Fuc residues linked via α1,2/3/4/6 bounds to oligosaccharide chains has also been related to increased aggressiveness in thyroid cancer [\u003cspan citationid=\"CR99\" class=\"CitationRef\"\u003e99\u003c/span\u003e, \u003cspan citationid=\"CR105\" class=\"CitationRef\"\u003e105\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cem\u003eTF glycotope\u003c/em\u003e The Thomsen-Friedenreich glycotope is exposed during tumorigenesis due to the defect of glycosyltransferases and chaperones involved in the elongation of the O-glycans [\u003cspan citationid=\"CR129\" class=\"CitationRef\"\u003e129\u003c/span\u003e]. The interactions mediated by its overexpression play an important role in thyroid, colon, prostate, and bone cancers [\u003cspan citationid=\"CR91\" class=\"CitationRef\"\u003e91\u003c/span\u003e, \u003cspan citationid=\"CR102\" class=\"CitationRef\"\u003e102\u003c/span\u003e, \u003cspan citationid=\"CR130\" class=\"CitationRef\"\u003e130\u003c/span\u003e, \u003cspan citationid=\"CR131\" class=\"CitationRef\"\u003e131\u003c/span\u003e], including tumor cell attachment to vascular endothelial cells (ECs), invasion and migration [\u003cspan citationid=\"CR102\" class=\"CitationRef\"\u003e102\u003c/span\u003e, \u003cspan additionalcitationids=\"CR133 CR134\" citationid=\"CR132\" class=\"CitationRef\"\u003e132\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR135\" class=\"CitationRef\"\u003e135\u003c/span\u003e]. The TF antigen is overexpressed in the membrane and cytoplasm of different cells of PTC tissues in comparison to human normal thyroid [\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e, \u003cspan citationid=\"CR91\" class=\"CitationRef\"\u003e91\u003c/span\u003e, \u003cspan citationid=\"CR98\" class=\"CitationRef\"\u003e98\u003c/span\u003e, \u003cspan additionalcitationids=\"CR103\" citationid=\"CR102\" class=\"CitationRef\"\u003e102\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR104\" class=\"CitationRef\"\u003e104\u003c/span\u003e]. In adult normal tissues, the TF glycotope is masked by sialic acid (sTF) [\u003cspan citationid=\"CR91\" class=\"CitationRef\"\u003e91\u003c/span\u003e, \u003cspan citationid=\"CR102\" class=\"CitationRef\"\u003e102\u003c/span\u003e, \u003cspan citationid=\"CR130\" class=\"CitationRef\"\u003e130\u003c/span\u003e, \u003cspan additionalcitationids=\"CR137 CR138 CR139\" citationid=\"CR136\" class=\"CitationRef\"\u003e136\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR140\" class=\"CitationRef\"\u003e140\u003c/span\u003e]. The GLL-II can react with the TF present in the PTC tissues, but not with the sTF form in normal thyroid, as the lectin does not interact with sialylated glycotopes [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Mucin-1 (MUC1) is a common carrier of TF in PTC, and mucin altered glycosylation reduces the interaction with E-selectin, leading to greater invasive and metastatic capacities. MUC1-TF is overexpressed at the apical and lateral membranes in PTC cancer cells [\u003cspan citationid=\"CR91\" class=\"CitationRef\"\u003e91\u003c/span\u003e], sites that coincide with the intense GLL-II staining in PTC follicular cell membrane (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed), in contrast to the diffuse cytoplasmic binding pattern predominant in FTC when TF-specific lectins have been used [\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e, \u003cspan citationid=\"CR104\" class=\"CitationRef\"\u003e104\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe high expression of α1,2-fucosylated glycotopes (H-type-II, Le\u003csup\u003eY\u003c/sup\u003e, Le\u003csup\u003eB\u003c/sup\u003e, globo-H glycosphingolipid) and TF antigen shows the potential utility of these glycan structures as biomarkers for PTC tissues. Multivariate analyses have indicated a strong association between the globo-H and MUC1-TF expressions with the presence of the BRAF-phenotype and lymph node metastasis [\u003cspan citationid=\"CR123\" class=\"CitationRef\"\u003e123\u003c/span\u003e, \u003cspan citationid=\"CR141\" class=\"CitationRef\"\u003e141\u003c/span\u003e]. Since those glycotopes are exposed in a greater proportion in PTC cell membranes than in FTC, it could be hypothesized that they play a role in promote the first steps of the BRAF-transcriptomic profile observed in PTC [\u003cspan citationid=\"CR83\" class=\"CitationRef\"\u003e83\u003c/span\u003e, \u003cspan citationid=\"CR84\" class=\"CitationRef\"\u003e84\u003c/span\u003e]. At the same time, the typical RAS-signaling in FTC would depend on other types of glycotopes. Future research into the relationship between the type of membrane glycoconjugates and transcriptomics could support the distinction between the different TC types in more detail.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eInvasive encapsulated follicular variant papillary thyroid carcinoma (IEFV-PTC)\u003c/h2\u003e \u003cp\u003eIn IEFV-PTC tissues, intense and moderate GLL-II staining was present in the Golgi complex (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). That organelle\u0026acute;s unique and specific label has not been described before in thyroid cancer. This result could be related to failures in transporting newly synthesized glycoconjugates (containing GLL-II ligands) from Golgi to other cellular areas in thyroid cells of IEFV-PTC patients.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e\u003c/h2\u003e \u003cp\u003eMalfunctioned Golgi apparatus plays pivotal roles in multiple human cancers [\u003cspan additionalcitationids=\"CR143 CR144 CR145\" citationid=\"CR142\" class=\"CitationRef\"\u003e142\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR146\" class=\"CitationRef\"\u003e146\u003c/span\u003e]. In the secretory pathway, once exported from the endoplasmic reticulum (ER) and reaching the \u003cem\u003etrans\u003c/em\u003e-side of the Golgi, newly synthesized cargos are packed into membrane carries destined for specific sites of cells \u003cem\u003ei.e\u003c/em\u003e., cell membrane or endolysosomes, or secreted outside [\u003cspan additionalcitationids=\"CR147 CR148\" citationid=\"CR146\" class=\"CitationRef\"\u003e146\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR149\" class=\"CitationRef\"\u003e149\u003c/span\u003e]. Recently, it was uncovered that the glycans could function as a generic Golgi export signal at the \u003cem\u003etrans\u003c/em\u003e-Golgi for constitutive exocytic trafficking; this mechanism can be alternative or complementary to the conventional amino acid short stretch signals that are recognized by diverse trafficking machineries [\u003cspan citationid=\"CR92\" class=\"CitationRef\"\u003e92\u003c/span\u003e]. By using superresolution microscopy, Golgi disassemblers and blockers of the O-GalNAc extension, it was observed that secretory cargos displayed substantial Golgi localization when their O-glycosylation is truncated, compared with the extended O\u003cem\u003e-\u003c/em\u003eglycans, which promote the Golgi export [\u003cspan citationid=\"CR92\" class=\"CitationRef\"\u003e92\u003c/span\u003e]. In that scenery, the Golgi specific GLL-II staining in IEFV-PTC carcinoma (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) could be due to higher expression of truncated O-glycans (\u003cem\u003eeg\u003c/em\u003e., Tn glycotope) in the Golgi trapped glycoproteins. Then, poor functioning/low expression level of glycosyltransferases that extend the O-glycosylation and/or failures in the protein transport system (\u003cem\u003eeg\u003c/em\u003e., glycan receptors, enzymes; free or in vesicles) would be characteristics in IEFV-PTC. Current and future research in Golgi functioning and glycosylation [\u003cspan citationid=\"CR143\" class=\"CitationRef\"\u003e143\u003c/span\u003e] could show more refined differences between the footprints in the tissues of the distinct thyroid tumor types, including IEFV-PTC.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eNon-neoplastic thyroid with goiter changes\u003c/h2\u003e \u003cp\u003eIn non-neoplastic thyroid with goiter changes, the GLL-II showed blood vessel staining, cytoplasmic granular label in follicular and C-cells, and non-uniform in colloid (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). While adult normal thyroid epithelial cells are H-type-II deficient [\u003cspan citationid=\"CR95\" class=\"CitationRef\"\u003e95\u003c/span\u003e, \u003cspan citationid=\"CR97\" class=\"CitationRef\"\u003e97\u003c/span\u003e, \u003cspan citationid=\"CR120\" class=\"CitationRef\"\u003e120\u003c/span\u003e, \u003cspan citationid=\"CR125\" class=\"CitationRef\"\u003e125\u003c/span\u003e], the vascular ECs do express that glycotope [\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e, \u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e, \u003cspan citationid=\"CR95\" class=\"CitationRef\"\u003e95\u003c/span\u003e, \u003cspan citationid=\"CR101\" class=\"CitationRef\"\u003e101\u003c/span\u003e, \u003cspan citationid=\"CR150\" class=\"CitationRef\"\u003e150\u003c/span\u003e]. It has been reported that the α1,2-fucosylated trisaccharide can participate in cell adhesion on endothelia through its interaction with some galectins [\u003cspan citationid=\"CR150\" class=\"CitationRef\"\u003e150\u003c/span\u003e]. On the other hand, the TF antigen is also present in ECs, and it is critical for the vascular integrity [\u003cspan citationid=\"CR151\" class=\"CitationRef\"\u003e151\u003c/span\u003e]. Both GLL-II (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e) as well as UEA-I [\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e] mark the vascular ECs as these structures contain receptors carrying exposed ligands for the two lectins [\u003cspan citationid=\"CR101\" class=\"CitationRef\"\u003e101\u003c/span\u003e, \u003cspan citationid=\"CR135\" class=\"CitationRef\"\u003e135\u003c/span\u003e, \u003cspan citationid=\"CR150\" class=\"CitationRef\"\u003e150\u003c/span\u003e], \u003cem\u003ei.e\u003c/em\u003e., H-type-II (shared ligand), Le\u003csup\u003eY\u003c/sup\u003e (UEA-I), TF (GLL-II), and Tn (GLL-II) glycotopes. The label of vascular endothelia using GLL-II or UEA-I is independent of the patient\u0026acute;s ABH blood type, so both lectins could be useful to demonstrate small vessel invasion. On the other hand, the moderate C-cell labeling with GLL-II coincides with the pattern previously observed in those cells using H-type-II-specific lectins in neoplastic and non-neoplastic thyroid tissues [\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn some thyroid goiter samples it was observed moderate irregular colloid staining with GLL-II (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ec). The colloid is composed mainly of the highly glycosylated prohormone thyroglobulin (Tg), which carryies N-glycans containing high mannose, sialylated, α1,6-fucosylated, bisecting, and LacNAc glycotopes [\u003cspan citationid=\"CR152\" class=\"CitationRef\"\u003e152\u003c/span\u003e]. A single chondroitin sulfate unit is linked to the residue Ser2730 [\u003cspan citationid=\"CR153\" class=\"CitationRef\"\u003e153\u003c/span\u003e], however, the precise structure of other O-glycans on Tg is still unknown [\u003cspan citationid=\"CR90\" class=\"CitationRef\"\u003e90\u003c/span\u003e]. None of the Tg glycotope structures reported above represents a GLL-II ligand. Meanwhile, colloid is TF-deficient [\u003cspan citationid=\"CR91\" class=\"CitationRef\"\u003e91\u003c/span\u003e]; and colloid in benign goiter has showed weak positive reaction to Forssman-specific lectins [\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e]. The moderate staining with GLL-II (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ec) and UEA-I [\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e] evidences a probable increase in the H-type-II glycotope in non-neoplastic thyroid with goiter changes, which could be verified in the future using other platforms.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eHashimoto\u0026rsquo;s thyroiditis (HT)\u003c/h2\u003e \u003cp\u003eThe common autoimmune thyroid disorder HT is characterized by marked lymphocyte and plasma cell infiltration of the parenchyma and antibodies specific to thyroid antigens [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan additionalcitationids=\"CR155\" citationid=\"CR154\" class=\"CitationRef\"\u003e154\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR156\" class=\"CitationRef\"\u003e156\u003c/span\u003e]. The thyroid structure can be destroyed by activated T-lymphocytes inducing chronic inflammation and the late-stage disease can resemble the histology of lymphatic tissue [\u003cspan citationid=\"CR156\" class=\"CitationRef\"\u003e156\u003c/span\u003e, \u003cspan citationid=\"CR157\" class=\"CitationRef\"\u003e157\u003c/span\u003e]. Inflammatory infiltrates in tumor tissue may represent a condition preceding the development of malignancy, and that is how HT can be frequently observed in PTC, and immune dysregulation is involved in both disorders [\u003cspan citationid=\"CR158\" class=\"CitationRef\"\u003e158\u003c/span\u003e]. In the HT tissues, the GLL-II staining was observed in the germinal center of the lymphoid follicles and, in some cases, in the apical and granular cytoplasmic portions of the follicular cells (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). The GLL-II label of lymphoid follicles is in agreement with the presence of the H-type-II and TF glycotopes, which in conjunction with sialofucosylated glycotopes (sLe\u003csup\u003eX\u003c/sup\u003e, sLe\u003csup\u003eA\u003c/sup\u003e, and 6-sulfo sLe\u003csup\u003eX\u003c/sup\u003e) and hyaluronic acid, regulate the adhesion/rolling of leukocytes migrating to the inflammation sites, interacting with carbohydrate binding proteins as galectin-9, galectin-3, selectins and CD44, respectively [\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e, \u003cspan citationid=\"CR135\" class=\"CitationRef\"\u003e135\u003c/span\u003e, \u003cspan citationid=\"CR150\" class=\"CitationRef\"\u003e150\u003c/span\u003e, \u003cspan citationid=\"CR151\" class=\"CitationRef\"\u003e151\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eThyroid biological sample source and glycosylation\u003c/h2\u003e \u003cp\u003eGlycosylation differs in pathological when compared to healthy conditions, and in turn some features also depend on the source of the biological sample, \u003cem\u003ei.e\u003c/em\u003e., tissues or fluids. Using sialic acid-binding lectins, mAb, and MALDI-TOF approaches, it was found upregulation of α2,6-sialylated glycans in both thyroid tissue and plasma of PTC patients [\u003cspan additionalcitationids=\"CR86\" citationid=\"CR85\" class=\"CitationRef\"\u003e85\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR87\" class=\"CitationRef\"\u003e87\u003c/span\u003e, \u003cspan citationid=\"CR98\" class=\"CitationRef\"\u003e98\u003c/span\u003e, \u003cspan citationid=\"CR159\" class=\"CitationRef\"\u003e159\u003c/span\u003e, \u003cspan citationid=\"CR160\" class=\"CitationRef\"\u003e160\u003c/span\u003e]; as well as downregulation of high-mannose type N\u003cem\u003e-\u003c/em\u003eglycans was found in both types of PTC samples [\u003cspan citationid=\"CR85\" class=\"CitationRef\"\u003e85\u003c/span\u003e, \u003cspan additionalcitationids=\"CR88\" citationid=\"CR87\" class=\"CitationRef\"\u003e87\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR89\" class=\"CitationRef\"\u003e89\u003c/span\u003e]. On the other hand, fucosylation and complex type N\u003cem\u003e-\u003c/em\u003eglycans increase in PTC tissues [\u003cspan citationid=\"CR85\" class=\"CitationRef\"\u003e85\u003c/span\u003e] while both decrease in plasma and serum N-glycome of PTC patients [\u003cspan citationid=\"CR87\" class=\"CitationRef\"\u003e87\u003c/span\u003e, \u003cspan citationid=\"CR88\" class=\"CitationRef\"\u003e88\u003c/span\u003e] when compared with the respective healthy controls.\u003c/p\u003e \u003cp\u003eIncreased levels of terminal mono- and disaccharide α/β-GalNAc glycotopes are present in HT patient\u0026acute;s thyroid tissue and blood [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e]. However, unlike HT tissues, low levels of α1,2-Fuc have been detected in the glycan antennas of HT peripheral blood mononuclear cells (PBMCs) [\u003cspan citationid=\"CR90\" class=\"CitationRef\"\u003e90\u003c/span\u003e], and high levels of sialylated glycans are present in the sera of HT patients with advanced thyroid destruction [\u003cspan citationid=\"CR157\" class=\"CitationRef\"\u003e157\u003c/span\u003e]. The increase in serum glycoconjugate sialylation is related to the presence of the β-galactoside α2,6-sialyltransferase 1 (ST6Gal1), which is active in the bloodstream of the HT patients, independently from the classical pathway of cellular glycosylation in ER and Golgi [\u003cspan citationid=\"CR157\" class=\"CitationRef\"\u003e157\u003c/span\u003e, \u003cspan citationid=\"CR161\" class=\"CitationRef\"\u003e161\u003c/span\u003e]. In this regard, it has been pointed out that the process of IgG sialylation may explain the great dynamics of inflammatory processes mediated by antibodies in HT [\u003cspan citationid=\"CR161\" class=\"CitationRef\"\u003e161\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003ePotential uses of GLL-II lectin in diagnostic of other conditions\u003c/h2\u003e \u003cp\u003eDetermination of the H-type-II glycotope as the predominant ligand of GLL-II allows us to propose this lectin as part of lectin-based diagnostic platforms that permit differentiating samples where the glycotope expression levels differ between healthy and pathological states. In addition to the patterns observed in neoplastic and non-neoplastic thyroid tissues (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e), in the consulted bibliography, we found other cases that show differences in the expression of the H-type-II glycotope in different conditions. For example, the H-type-II glycotope is among the overexpressed motifs in serum samples from patients with squamous cell carcinoma (SCC) of non-small cell lung cancer (NSCLC) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] or prostate cancer [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], and in biopsies from patients with gastric cancer [\u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] or \u003cem\u003eHelicobacter pylori\u003c/em\u003e-infected [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]; compared to the healthy conditions or other pathologies in the same organs (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePotential uses of GLL-II lectin in the diagnosis of human organism conditions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCondition\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSample\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eChanges in glycosylation patterns\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePotential\u003c/p\u003e \u003cp\u003eGLL-II appication\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eExpected results using GLL-II\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOverexpression in pathological\u003c/p\u003e \u003cp\u003eCondition\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh expression in healthy/different condition\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThyroid\u003c/p\u003e \u003cp\u003ebiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH-type-II, Globo-H, Le\u003csup\u003eY\u003c/sup\u003e, α1,6-Fuc; TF, LacdiNAc, Forssman, terminal GlcNAcα/β, poly-IIβ, Siaα2,6-Tn; Siaα2,3-Le\u003csup\u003eX\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSiaα2,3-IIβ and oligomannosides.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDifferentiate between PTC and healthy control.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh signal intensity in FC apical membrane and cytoplasm in tissue of PTC patients\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSCC- NSCLC pulmonary cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSerum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH-type-II; α1,2/6-Fuc; Siaα2,3-TF, LacDiNAc; 3/6-O-sulfated-TF; GlcNAcβ1,4/6Man; Group A; Group B; terminal Man\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSiaα2,6-Iβ/IIβ;\u003c/p\u003e \u003cp\u003eα1,3-Fuc (Le\u003csup\u003eX\u003c/sup\u003e/Le\u003csup\u003eY\u003c/sup\u003e), poly-IIβ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDifferentiate between SCC carcinoma and healthy control.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh signal intensity in serum from patients with SCC carcinoma in NSCLC.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProstate cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSerum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH-types-II/III/IV; α1,2/6-Fuc; LacDiNAc; Poly-IIβ; α/β-GalNAc; Siaα2,3-IIβ/Le\u003csup\u003eX\u003c/sup\u003e/TF;\u003c/p\u003e \u003cp\u003e3/6-O-sulfated-IIβ;\u003c/p\u003e \u003cp\u003eGlcNAcβ1,4Man\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSiaα2,6-IIβ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDifferentiate between prostate cancer and benign prostatic hyperplasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh signal intensity in serum from patients with prostate cancer.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastric cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGastric\u003c/p\u003e \u003cp\u003ebiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH-type-II; α1,2/6-Fuc; α/β-Gal/GalNAc; Siaα2,3-TF/Le\u003csup\u003eA\u003c/sup\u003e/Le\u003csup\u003eX\u003c/sup\u003e;\u003c/p\u003e \u003cp\u003eGlcNAcβ1,4/6Man; Siaα2,6-LacDiNAc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMulti/poly-IIβ on branched N-glycans in gastric ulcer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDiscriminate gastric cancer from gastric ulcer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh signal intensity in gastric tissues from patients with gastric cancer.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eH. pylori\u003c/em\u003e infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGastric body biopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH-type-II; Le\u003csup\u003eX\u003c/sup\u003e/Le\u003csup\u003eY\u003c/sup\u003e;\u003c/p\u003e \u003cp\u003eSiaα2,6Gal/GalNAc.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGlcNAcβ1,2/4-Man; terminal α1,3/6-Man; IIβ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDiscriminate infected from uninfected patient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh signal intensity in gastric mucosa of infected patient.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAquilles\u003c/em\u003e tendon rupture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEV derived from bone marrow MSC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLower level of Fucα1,2 in non-regenerative EV.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eα1,2-fucosylated glycoconjugates in regenerative EV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEstablish an isolation system of regenerative EVs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh signal intensity in EV with Aquilles tendon regenerative potential\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood\u003c/p\u003e \u003cp\u003etyping\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHuman RBCs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eABO groups\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRecognize\u003c/p\u003e \u003cp\u003eO-type RBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSpecific O-type RBC agglutination\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eEV: extracellular vesicles. FC: follicular cells. Iβ: LacNAc-I. IIβ: LacNAc-II. Le: Lewis antigens A, Y or X. MSC: mesenchymal stem cells. SCC: squamous cell carcinoma. Sia: sialic acid. Data: Aquilles tendon rupture [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]; Blood typing [Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and S2], Gastric cancer [\u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]; \u003cem\u003eH. pylori\u003c/em\u003e infection [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]; NSCLC: non-small cell lung cancer [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]; PTC: Papillary Thyroid Carcinoma [77, 85\u0026ndash;87, 90, 98, 103, 104, 112, 124, and present work]; Prostate cancer [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The predominant ligands of the lectins used in the different studies have been updated as described in [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBy associating the differences and similarities between the H-type-II-recognizing lectins and the glycosylation changes reported in different states of the organism (Tables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), some considerations regarding to the glycotopes overexpressed under the opposite physiological conditions should be considered. For example, in the discrimination of patients with pulmonary SCC carcinoma, H-type-II glycotope levels are overexpressed in serum in the pathological condition, while those of the antigen Le\u003csup\u003eY\u003c/sup\u003e are high in healthy sera [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. For this reason, it is relevant that in platforms for the diagnosis of that type of cancer, along with the UEA-I lectin (which recognizes both H-type-II and Le\u003csup\u003eY\u003c/sup\u003e), another H-type-II-specific lectin that does not recognize Le\u003csup\u003eY\u003c/sup\u003e (\u003cem\u003ee.g\u003c/em\u003e., GLL-II), should also be included. Conversely, UEA-I could be very valuable in diagnosing of \u003cem\u003eH. pylori\u003c/em\u003e infection where overexpression of both glycotopes occurs in the infected gastric body [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. On the other hand, as terminal α1,2-Fuc is a biomarker of those extracellular vesicles (EV) derived from bone marrow mesenchymal stem cells (MSC) that have the potential to promote regeneration of Achilles tendon that has experienced rupture [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], then GLL-II, UEA-I and TJA-II could be tested as the basis of an isolation system for regenerative EVs; as well as, the three lectins may be useful in the diagnosis of prostate cancer due the overexpression of the H-type-II (GLL-II and UEA-I), and H-type-III/IV (TJA-II) glycotopes in the patient sera [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. As described in previous sections, GLL-II and UEA-I are useful lectins in the discrimination between normal thyroid tissue and some thyroid alterations due the overexpression of GLL-II and UEA-I ligands depending on thyroid disorder.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe GLL-II lectin has high useful potential in diagnostic platforms due its ligands (H-type-II, TF, and Tn glycotopes) are unregulated in unhealthy conditions, allowing to distinguish between healthy and pathological states samples. Due to its high specificity towards the H-type-II glycotope, GLL-II shows great potential as a tool in the detection of this overexpressed biomarker in PTC, gastric cancer, and \u003cem\u003eH.\u003c/em\u003e pylori-infected biopsies, as well as in serum of patients of SCC-NSCLC and prostate cancer. Besides, the existing evidence of the presence of the TF structure in PTC, as well as of Tn antigen in gastric cancer biopsies and in the serum of prostate cancer patients, represents an additive advantage when using GLL-II for diagnosing those conditions. Additionally, GLL-II could be tested as the basis of an isolation system for regenerative EVs. For the above, we consider the inclusion of GLL-II in lectin-based diagnostic platforms plausible, taking advantage of the progress in the study of its specificity.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Dr. Fern\u0026aacute;ndez J.L. (from the Universidad Nacional Institute of Natural Sciences) for plant species identification. Financial support was provided by the Universidad Nacional Chemistry Department; and by the Ministry of Science, Technology and Innovation of Colombia (MinCiencias) with the Lamiaceae Lectin Structure project grant 110148925106 and the doctoral student grant 617 - 0656 (T.M.C).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy conception, design, material preparation, data collection, and analysis, were performed by all authors. The first draft of the manuscript was written by T.M.C., N.A.V., and E.A.R.M. All authors commented on previous versions of the manuscript and read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOther declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo study the native species \u003cem\u003eGalactia lindenii\u003c/em\u003e, the contract code for access to genetic resources granted by the Ministry of Environment and Sustainable Development of Colombia was number 246.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was carried out following the approval of the Research Ethics Committee at Universidad Nacional de Colombia (Protocol INC GT00035). Informed consent was obtained from all patients before collecting samples for analysis. This research was classified as a minimal-risk study following the guidelines outlined in the document \u0026quot;RESOLUCI\u0026Oacute;N 8430 DE 1993\u0026quot; on Ethical Aspects of Human Research (Title II, Chapter 1) published by the Ministry of Health of Colombia.. The samples from the analyses outlined in this project were handled according to the biosafety protocols endorsed by the national and international scientific community, as regulated by the Ministry of Social Protection of Colombia in the Resolution 8430 of 1993.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDe Coninck, T., Van Damme, E.J.M.: Review: The multiple roles of plant lectins. Plant. Sci. 313 (2021). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.plantsci.2021.111096\u003c/span\u003e\u003cspan address=\"10.1016/j.plantsci.2021.111096\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVerkerke, H., Dias-Baruffi, M., Cummings, R.D., Arthur, C.M., Stowell, S.R.: Galectins: An Ancient Family of Carbohydrate Binding Proteins with Modern Functions. In: Stowell, S.R., Arthur, C.M., Cummings, R.D. (eds.) Galectins. Methods in Molecular Biology, vol 2442, pp 1\u0026ndash;40. Humana, New York, NY (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/978-1-0716-2055-7_1\u003c/span\u003e\u003cspan address=\"10.1007/978-1-0716-2055-7_1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAndr\u0026eacute;, S., Kaltner, H., Manning, J.C., Murphy, P.V., Gabius, H.J.: Lectins: getting familiar with translators of the sugar code. Molecules. 20(2):1788\u0026ndash;1823 (2015). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/molecules20021788\u003c/span\u003e\u003cspan address=\"10.3390/molecules20021788\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMishra, A., Behura, A., Mawatwal, S., Kumar, A., Naik, L., Mohanty, S.S., Manna, D., Dokania, P., Mishra, A.: Structure-function and application of plant lectins in disease biology and immunity. Food. Chem. Toxicol. 134 (2019). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.fct.2019.110827\u003c/span\u003e\u003cspan address=\"10.1016/j.fct.2019.110827\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMattox, D.E., Baiyley-Kellogg, C.: Comprehensive analysis of lectin-glycan interactions reveals determinants of lectin specificity. Plos. Comput. Biol. (2021). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1371/journal.pcbi.1009470\u003c/span\u003e\u003cspan address=\"10.1371/journal.pcbi.1009470\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCummings, R.D., Etzler, M.E., Hahn, M.G., Darvil, A., Godula, K., Woods, R.J., Mahal, L.K.: Glycan-Recognizing Probes as Tools. In: Varki, A., Cummings, R.D., Esko, J.D., Stanley, P., Hart, G.W., Aebi, M., Mohnen, D., Kinoshita, T., Packer, N.H., Prestegard, J.H., Schnaar, R.L., Seeberger, P.H., (eds.) Essentials of Glycobiology. 4th ed, Chap. 48. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/books/NBK579992/\u003c/span\u003e\u003cspan address=\"https://www.ncbi.nlm.nih.gov/books/NBK579992/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCummings, R.D., Pierce, J.M.: The challenge and promise of glycomics. Chem. Biol. 21(1):1\u0026ndash;15 (2014). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.chembiol.2013.12.010\u003c/span\u003e\u003cspan address=\"10.1016/j.chembiol.2013.12.010\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaab, B.B., Klamer. Z.: Advances in Tools to Determine the Glycan-Binding Specificities of Lectins and Antibodies. Mol. Cell. Proteomics. 19(2):224\u0026ndash;232 (2020). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000120/\u003c/span\u003e\u003cspan address=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000120/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGalili, U.: Human Natural Antibodies to Mammalian Carbohydrate Antigens as Unsung Heroes Protecting against Past, Present, and Future Viral Infections. Antibodies (Basel). 9(2):25 (2020). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/antib9020025\u003c/span\u003e\u003cspan address=\"10.3390/antib9020025\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIskratsch, T., Braun, A., Paschinger, K., Wilson, I.B.H.: Specificity analysis of lectins and antibodies using remodeled glycoproteins. Anal. Biochem. 386(2):133\u0026ndash;146 (2009). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ab.2008.12.005\u003c/span\u003e\u003cspan address=\"10.1016/j.ab.2008.12.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou, D., Xu, L., Huang, W., Tonn, T.: Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy. Molecules. 23(6):1326 (2018). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/molecules23061326\u003c/span\u003e\u003cspan address=\"10.3390/molecules23061326\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMollicone, R., Cailleau, A., Imberty, A., Gane, P., Perez, S., Oriol, R.: Recognition of the blood group H type 2 trisaccharide epitope by 28 monoclonal antibodies and three lectins. Glycoconj. J. 13(2):263\u0026ndash;271 (1996). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/BF00731501\u003c/span\u003e\u003cspan address=\"10.1007/BF00731501\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollins, B.C., Gunn, R.J., McKitrick, T.R., Cummings, R.D., Cooper, M.D., Herrin, B.R., Wilson, I.A.: Structural Insights into VLR Fine Specificity for Blood Group Carbohydrates. Structure. 25(11):1667\u0026ndash;1678. E4. (2017). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.str.2017.09.003\u003c/span\u003e\u003cspan address=\"10.1016/j.str.2017.09.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKappler, K., Hennet, T.: Emergence and significance of carbohydrate-specific antibodies. Genes. Immun. 21, 224\u0026ndash;239 (2020). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.nature.com/articles/s41435-020-0105-9\u003c/span\u003e\u003cspan address=\"https://www.nature.com/articles/s41435-020-0105-9\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDang, K., Zhang, W., Jiang, S., Lin, X., Qian, A.: Application of lectin microarrays for biomarker discovery. ChemistryOpen. 9(3):285\u0026ndash;300 (2020). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/open.201900326\u003c/span\u003e\u003cspan address=\"10.1002/open.201900326\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBojar, D., Meche, L., Meng, G., Eng, E., Smith, D.F., Cummings, R.D., Mahal, L.K.: A Useful Guide to Lectin Binding: Machine-Learning Directed Annotation of 57 Unique Lectin Specificities. ACS Chem. Biol. 17(11):2993\u0026ndash;3012 (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1021/acschembio.1c00689\u003c/span\u003e\u003cspan address=\"10.1021/acschembio.1c00689\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDefaus, S., Gupta, P., Andreu, D., Guti\u0026eacute;rrez-Gallego, R.: Mammalian protein glycosylation\u0026ndash;structure versus function. Analyst. 139(12):2944\u0026ndash;2967 (2014). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1039/C3AN02245E\u003c/span\u003e\u003cspan address=\"10.1039/C3AN02245E\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOgawa, R., Okimoto, T., Kodama, M., Togo, K., Fukuda, K., Okamoto, K., Mizukami, K., Murakami, K.: Changes in Gastric Mucosal Glycosylation Before and After Helicobacter pylori Eradication Using Lectin Microarray Analysis. Turk. J. Gastroenterol. 33(2):88\u0026ndash;94 (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5152/tjg.2021.201116\u003c/span\u003e\u003cspan address=\"10.5152/tjg.2021.201116\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiang, Y., Han, P., Wang, T., Ren, H., Gao, L., Shi, P., Zhang, S., Yang, A., Li, Z., Chen, M.: Stage-associated differences in the serum N- and O-glycan profiles of patients with non-small cell lung cancer. Clin. Proteomics. 16:20 (2019). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12014-019-9240-6\u003c/span\u003e\u003cspan address=\"10.1186/s12014-019-9240-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFukushima, K., Satoh, T., Baba, S., Yamashita, K.: alpha1,2-Fucosylated and beta-N-acetylgalactosaminylated prostate-specific antigen as an efficient marker of prostatic cancer. Glycobiology. 20(4):452\u0026ndash;460 (2010). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/glycob/cwp197\u003c/span\u003e\u003cspan address=\"10.1093/glycob/cwp197\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTokuda, N., Zhang, Q., Yoshida, S., Kusunoki, S., Urano, T., Furukawa, K., Furukawa, K.: Genetic mechanisms for the synthesis of fucosyl GM1 in small cell lung cancer cell lines. Glycobiology. 16(10): 916\u0026ndash;925 (2006). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/glycob/cwl022\u003c/span\u003e\u003cspan address=\"10.1093/glycob/cwl022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTkac, J., Gajdosova, V., Hroncekova, S., Bertok, T., Hires, M., Jane, E., Lorencova, L., Kasak, P.: Prostate-specific antigen glycoprofiling as diagnostic and prognostic biomarker of prostate cancer. Interface. Focus. 9(2):20180077 (2019). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://doi.org/10.1098/rsfs.2018.0077\u003c/span\u003e\u003cspan address=\"10.1098/rsfs.2018.0077\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang, W.L., Li, Y.G., Lv, Y.C., Guan, X.H., Ji, H.F., Chi, B.R.: Use of lectin microarray to differentiate gastric cancer from gastric ulcer. World. J. Gastroenterol. 20(18):5474\u0026ndash;5482 (2014). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.3748/wjg.v20.i18.5474\u003c/span\u003e\u003cspan address=\"10.3748/wjg.v20.i18.5474\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDuarte, H.O., Rodrigues, J.G., Gomes, C., Hensbergen, P.J., Ederveen, A.L.H, de Ru, A.H., Mereiter, S., Pol\u0026oacute;nia, A., Fernandes, E., Ferreira, J.A., van Veelen, P.A., Santos, L.L., Wuhrer, M., Gomes, J., Reis, C.A.: ST6Gal1 targets the ectodomain of ErbB2 in a site-specific manner and regulates gastric cancer cell sensitivity to trastuzumab. Oncogene. 40(21):3719\u0026ndash;3733 (2021). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41388-021-01801-w\u003c/span\u003e\u003cspan address=\"10.1038/s41388-021-01801-w\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGomes, C., Almeida, A., Barreira, A., Calheiros, J., Pinto, F., Abrantes, R., Costa, A., Polonia, A., Campos, D., Os\u0026oacute;rio, H., Sousa, H., Pinto-de-Sousa, J., Kolarich, D., Reis, C.A.: Carcinoembryonic antigen carrying SLe\u003csup\u003eX\u003c/sup\u003e as a new biomarker of more aggressive gastric carcinomas. Theranostics. 9(24):7431\u0026ndash;7446 (2019). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.7150/thno.33858\u003c/span\u003e\u003cspan address=\"10.7150/thno.33858\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAziz, F., Khan, I., Shukla, S., Dey, D.K., Yan, Q., Chakraborty, A., Yoshitomi, H., Hwang, S.K., Sonwal, S., Lee, H., Haldorai, Y., Xiao, J., Huh, Y.S., Bajpai, V.K., Han, Y.K.: Partners in crime: The Lewis Y antigen and fucosyltransferase IV in Helicobacter pylori-induced gastric cancer. Pharmacol. Ther. 232:107994 (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.pharmthera.2021.107994\u003c/span\u003e\u003cspan address=\"10.1016/j.pharmthera.2021.107994\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHayashi, Y., Yimiti, D., Sanada, Y., Ding, C., Omoto, T., Ogura, T., Nakasa, T., Ishikawa, M., Hiemori, K., Tateno, H., Miyaki, S., Adachi, N.: The therapeutic capacity of bone marrow MSC-derived extracellular vesicles in Achilles tendon healing is passage-dependent and indicated by specific glycans. FEBS. Lett. 596(8):1047\u0026ndash;1058 (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/1873-3468.14333\u003c/span\u003e\u003cspan address=\"10.1002/1873-3468.14333\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu, Y., Huo, J., Nie, R., Ge, L., Xie, C., Meng, Y., Liu, J., Wu, L., Qin, X.: Altered profile of glycosylated proteins in serum samples obtained from patients with Hashimoto's thyroiditis following depletion of highly abundant proteins. Front. Immunol. 14:1182842 (2023). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.frontiersin.org/articles/\u003c/span\u003e\u003cspan address=\"https://www.frontiersin.org/articles/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2023.1182842/full\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2023.1182842/full\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Queiroz, L.P., Pastore, J.F., Cardoso, D., Snak, C., de C Lima, A.L., Gagnon, E., Vatanparast, M., Holland, A.E., Egan, A.N.: A multilocus phylogenetic analysis reveals the monophyly of a recircumscribed papilionoid legume tribe Diocleae with well-supported generic relationships. Mol. Phylogenet. Evol. 90:1\u0026ndash;19 (2015). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ympev.2015.04.016\u003c/span\u003e\u003cspan address=\"10.1016/j.ympev.2015.04.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlmanza, M., Vega, N., P\u0026eacute;rez, G.: Isolating and characterising a lectin from Galactia lindenii seeds that recognises blood group H determinants. Arch. Biochem. Biophys. 429(2):180\u0026ndash;190 (2004). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1016/j.abb.2004.06.010\u003c/span\u003e\u003cspan address=\"10.1016/j.abb.2004.06.010\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQuintero, M.: Elucidaci\u0026oacute;n parcial de la estructura primaria de la lectina LGL-P2 y purificaci\u0026oacute;n y caracterizaci\u0026oacute;n parcial de la lectina LGL-P4 presentes en semillas de Galactia lindenii. Tesis de Maestr\u0026iacute;a, Facultad de Ciencias, Departamento de Qu\u0026iacute;mica, Universidad Nacional de Colombia. Sede Bogot\u0026aacute;. (2014). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://repositorio.unal.edu.co/handle/unal/51820\u003c/span\u003e\u003cspan address=\"https://repositorio.unal.edu.co/handle/unal/51820\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCort\u0026aacute;zar, T.M., Wilson, I.B.H., Hykollari, A., Reyes, E.A., Vega, N.A.: Differential recognition of natural and remodeled glycotopes by three Diocleae lectins. Glycoconj. J. 35(2):205\u0026ndash;216 (2018). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s10719-018-9851-6\u003c/span\u003e\u003cspan address=\"10.1007/s10719-018-9851-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eP\u0026eacute;rez, G.: Isolation and characterization of a novel lectin from Dioclea lehmanni (Fabaceae) seeds. Int. J. Biochem. Cell. Biol. 30:843\u0026ndash;853 (1998). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S1357-2725(98)00045-4\u003c/span\u003e\u003cspan address=\"10.1016/S1357-2725(98)00045-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMelgarejo, L.M., Vega, N., P\u0026eacute;rez, G.: Isolation and characterization of novel lectins from Canavalia ensiformis DC and Dioclea grandiflora Mart. Ex Benth. seeds. Braz. J. Plant. Physiol. 17(3): 315\u0026ndash;324 (2005). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1590/S1677-04202005000300006\u003c/span\u003e\u003cspan address=\"10.1590/S1677-04202005000300006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDam, T.K., Cavada, B.S., Nagano, C.S., Rocha, B.A., Benevides, R.G., Nascimento, K.S., de Sousa, L.A., Oscarson, S., Brewer, C.F.: Fine specificities of two lectins from Cymbosema roseum seeds: a lectin specific for high-mannose oligosaccharides and a lectin specific for blood group H type II trisaccharide. Glycobiology. 21(7):925\u0026ndash;933 (2011). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/glycob/cwr025\u003c/span\u003e\u003cspan address=\"10.1093/glycob/cwr025\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCavada, B.S., Pinto-Junior, V.R., Osterne, V.J.S., Lossio, C.F., Silva, M.T.L., Correia, J.L.A., Correia, S.E.G., Nagano, C.S., Oliveira, M.V., Lima, L.D., Vital, A.P.M.S., Leal, R.B., Nascimento, K.S.: A Diocleinae type II lectin from Dioclea lasiophylla Mart. Ex Benth seeds specific to α-lactose/GalNAc. Process. Biochem. 93, 104\u0026ndash;114 (2020). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.procbio.2020.03.026\u003c/span\u003e\u003cspan address=\"10.1016/j.procbio.2020.03.026\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRocha, B.A.M., Moreno, F.B.M.B, Delatorre, P., Souza, E.P., Marinho, E.S., Benevides, R.G., Rustiguel, J.K.R., Souza, L.A.G., Nagano, C.S., Debray, H., Sampaio, A.H., de Azevedo Jr, W.F., Cavada, B.S.: Purification, characterization, and preliminary X-ray diffraction analysis of a lactose-specific lectin from Cymbosema roseum seeds. Appl. Biochem. Biotechnol. 152(3):383\u0026ndash;393 (2009). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s12010-008-8334-9\u003c/span\u003e\u003cspan address=\"10.1007/s12010-008-8334-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBatista, F.A.H, Goto, L.S., Garcia, W., Moraes, D.I., Neto, M.O., Polikarpov, I., Cominetti, M.R., Selistre-de-Ara\u0026uacute;jo, H.S., Beltramini, L.M., Araujo, A.P.U.: Camptosemin, a tetrameric lectin of Camptosema ellipticum: structural and functional analysis. Eur Biophys J. 39(8):1193\u0026ndash;1205 (2010). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://link.springer.com/article/\u003c/span\u003e\u003cspan address=\"https://link.springer.com/article/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00249-009-0571-5\u003c/span\u003e\u003cspan address=\"10.1007/s00249-009-0571-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eP\u0026eacute;rez, G., Hern\u0026aacute;ndez, M., Mora, E.: Isolation and characterization of a lectin from the seeds of Dioclea lehmanni. Phytochem. 29(6):1745\u0026ndash;1749 (1990). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/0031-9422(90)85007-3\u003c/span\u003e\u003cspan address=\"10.1016/0031-9422(90)85007-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDam, T.K., Cavada, B.S., Grangeiro, T.B., Santos, C.F., de Sousa, F.A., Oscarson, S., Brewer, C.F.: Diocleinae lectins are a group of proteins with conserved binding sites for the core trimannoside of asparagine-linked oligosaccharides and differential specificities for complex carbohydrates. J. Biol. Chem. 273(20):12082\u0026ndash;12088 (1998). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1074/jbc.273.20.12082\u003c/span\u003e\u003cspan address=\"10.1074/jbc.273.20.12082\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCalvete, J.J., Thole, H.H., Raida, M., Urbanke, C., Romero, A., Grangeiro, T.B., Ramos, M.V., Almeida da Rocha, I.M., Guimar\u0026atilde;es, F.N., Cavada, B.S.: Molecular characterization and crystallization of Diocleinae lectins. Biochim. Biophys. Acta. 1430(2):367\u0026ndash;375 (1999). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0167-4838(99)00020-5\u003c/span\u003e\u003cspan address=\"10.1016/s0167-4838(99)00020-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHermanson, G.T.: Immobilization of Ligands on Chromatography Supports. In: Audet, J., Preap, M. (eds.) Bioconjugate Techniques Third Edition. Elsevier, London, UK (2013). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1016/B978-0-12-382239-0.00015-7\u003c/span\u003e\u003cspan address=\"10.1016/B978-0-12-382239-0.00015-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmith, P.K., Krohn, R.I., Hermanson, G.T., Mallia, A.K., Gartner, F.H., Provenzano, M.D., Fujimoto, E.K., Goeke, N.M., Olson, B.J., Klenk, D.C.: Measurement of protein using Bicinchoninic Acid. Anal. Biochem. 150:76\u0026ndash;85 (1985). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi:10.1016/0003-2697(85)90442-7\u003c/span\u003e\u003cspan address=\"https://doi:10.1016/0003-2697(85)90442-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaemmli, U. K.: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 227(5259): 680\u0026ndash;685 (1970). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/227680a0\u003c/span\u003e\u003cspan address=\"10.1038/227680a0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIglesias, J.L., Lis, H., Sharon, N.: Purification and Properties of a D-Galactose/N-Acetyl-D-galactosamine-Specific Lectin from Erythrina cristagalli. Eur. J. Biochem. 123(2):247\u0026ndash;252 (1982). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1432-1033.1982.tb19760.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1432-1033.1982.tb19760.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHirohashi, S., Clausen, H., Yamada, T., Shimosato, Y., Hakomori, S.: Blood group A cross-reacting epitope defined by monoclonal antibodies NCC-LU-35 and \u0026ndash;\u0026thinsp;81 expressed in cancer of blood group O or B individuals: its identification as Tn antigen. Proc. Natl. Acad. Sci. USA. 82(20):7039\u0026ndash;7043 (1985). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1073/pnas.82.20.7039\u003c/span\u003e\u003cspan address=\"10.1073/pnas.82.20.7039\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoizumi, T., Matsumoto-Takasaki, A., Nakada, H., Nakata, M., Fujita-Yamaguchi, Y.: Preparation of asialo-agalacto-glycophorin A for screening of anti-Tn antibodies. BioSci. Trends. 4(6):308\u0026ndash;311 (2010).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu, A.M., Duk, M., Lin, M., Broadberry, R.E., Lisowska, E.: Identification of variant glycophorins of human red cells by lectinoblotting: Application to the Mi. III variant that is relatively frequent in the Taiwanese population. Transfusion. 35(7):571\u0026ndash;576 (1995). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1046/j.1537-2995.1995.35795357879.x\u003c/span\u003e\u003cspan address=\"10.1046/j.1537-2995.1995.35795357879.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEvans, S.V., MacKenzie, C.R.: Characterization of protein-glycolipid recognition at the membrane bilayer. J. Mol. Recognit. 12(3): 155\u0026ndash;168 (1999). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/(SICI)1099-1352(199905/06)12:3\u0026lt;155::AID-JMR456\u0026gt;3.0.CO;2-S\u003c/span\u003e\u003cspan address=\"10.1002/(SICI)1099-1352(199905/06)12:3%3C155::AID-JMR456%3E3.0.CO;2-S\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStanley, P., Wuhrer, M., Lauc, G., Stowell, S.R., Cummings, R.D.: Structures Common to Different Glycans. In: Varki, A., Cummings, R.D., Esko, J.D., Stanley, P., Hart, G.W., Aebi, M., Mohnen, D., Kinoshita, T., Packer, N.H., Prestegard, J.H., Schnaar, R.L., Seeberger, P.H, (eds.) Essentials of Glycobiology [Internet]. 4th Edition. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press (2022), Chap. 14. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1101/glycobiology.4e.1\u003c/span\u003e\u003cspan address=\"10.1101/glycobiology.4e.1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDean, L.: The ABO blood group. In: Blood Groups and Red Cell Antigens [Internet]. Bethesda (MD): National Center for Biotechnology Information (US) (2005), Chap. 5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/books/NBK2267/\u003c/span\u003e\u003cspan address=\"https://www.ncbi.nlm.nih.gov/books/NBK2267/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAoki, T.: A Comprehensive Review of Our Current Understanding of Red Blood Cell (RBC) Glycoproteins. Membranes (Basel). 7(4):56 (2017). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/membranes7040056\u003c/span\u003e\u003cspan address=\"10.3390/membranes7040056\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOgawa, H., Galili, U.: Profiling terminal N-acetyllactosamines of glycans on mammalian cells by an immuno-enzymatic assay. Glycoconj. J. 23(9):663\u0026ndash;674 (2006). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s10719-006-9005-0\u003c/span\u003e\u003cspan address=\"10.1007/s10719-006-9005-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIto, T., Suzuki, Y., Mitnaul, L., Vines, A., Kida, H., Kawaoka, Y.: Receptor specificity of influenza A viruses correlates with the agglutination of erythrocytes from different animal species.Virology. 227(2):493\u0026ndash;499 (1997). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1006/viro.1996.8323\u003c/span\u003e\u003cspan address=\"10.1006/viro.1996.8323\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAltman, M.O., Gagneux, P.: Absence of Neu5Gc and Presence of Anti-Neu5Gc Antibodies in Humans-An Evolutionary Perspective. Front. Immunol. 10:789 (2019). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fimmu.2019.00789\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2019.00789\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSreenivasan, C.C., Sheng, Z., Wang, D., Li, F.: Host Range, Biology, and Species Specificity of Seven-Segmented Influenza Viruses-A Comparative Review on Influenza C and D. Pathogens. 10(12):1583 (2021). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/pathogens10121583\u003c/span\u003e\u003cspan address=\"10.3390/pathogens10121583\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamamoto, T., Hara, H., Iwase, H., Jagdale, A., Bikhet, M.H., Morsi, M.A., Cui, Y., Nguyen, H.Q., Wang, Z.Y., Anderson, D.J., Foote, J., Schuurman, H.J., Ayares, D., Eckhoff, D.E., Cooper, D.KC.: The final obstacle to successful pre-clinical xenotransplantation? Xenotransplantation. 27(5):e12596 (2020). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/xen.12596\u003c/span\u003e\u003cspan address=\"10.1111/xen.12596\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeizi, T.: Demonstration by monoclonal antibodies that carbohydrate structures of glycoproteins and glycolipids are onco-developmental antigens. Nature. 314, 53\u0026ndash;57 (1985). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/314053a0\u003c/span\u003e\u003cspan address=\"10.1038/314053a0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchneider, M., Al-Shareffi, E., Haltiwanger, R.S.: Biological functions of fucose in mammals. Glycobiology. 27(7):601\u0026ndash;618 (2017). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/glycob/cwx034\u003c/span\u003e\u003cspan address=\"10.1093/glycob/cwx034\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRavn, V., Dabelsteen, E.: Tissue distribution of histo-blood group antigens. APMIS. 108(1):1\u0026ndash;28 (2000). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1034/j.1600-0463.2000.d01-1.x\u003c/span\u003e\u003cspan address=\"10.1034/j.1600-0463.2000.d01-1.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu, F., Qin, Y., Jiang, Q., Zhang, J., Li, F., Li, Q., Wang, X., Gao, Y., Miao, J., Guo, C., Yang, Y., Ni, L., Liu, L., Zhang, S., Huang C.: MyoD1 suppresses cell migration and invasion by inhibiting FUT4 transcription in human gastric cancer cells. Cancer. Gene. Ther. 27(10\u0026ndash;11):773\u0026ndash;784 (2020). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41417-019-0153-3\u003c/span\u003e\u003cspan address=\"10.1038/s41417-019-0153-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChessa, D., Winter, M.G., Jakomin, M., B\u0026auml;umler, A.J.: Salmonella enterica serotype Typhimurium Std fimbriae bind terminal alpha(1,2)fucose residues in the cecal mucosa. Mol. Microbiol. 71(4):864\u0026ndash;875 (2009). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1365-2958.2008.06566.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1365-2958.2008.06566.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArenas, M.I., Royuela, M., Fraile, B., Paniagua, R., Wilhelm, B., Aum\u0026uuml;ller, G.: Identification of N- and O-linked oligosaccharides in human seminal vesicles. J. Androl. 22(1):79\u0026ndash;87 (2001). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/j.1939-4640.2001.tb02156.x\u003c/span\u003e\u003cspan address=\"10.1002/j.1939-4640.2001.tb02156.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDall\u0026rsquo;Olio, F., Pucci, M., Malagolini, N.: The Cancer-Associated Antigens Sialyl Lewis\u003csup\u003ea/x\u003c/sup\u003e and Sd\u003csup\u003ea\u003c/sup\u003e: Two Opposite Faces of Terminal Glycosylation. Cancers. 13(21):5273 (2021). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/cancers13215273\u003c/span\u003e\u003cspan address=\"10.3390/cancers13215273\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePinho, S., Reis, C.: Glycosylation in cancer: mechanisms and clinical implications. Nat. Rev. Cancer. 15(9):540\u0026ndash;555 (2015). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/nrc3982\u003c/span\u003e\u003cspan address=\"10.1038/nrc3982\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThomas, D., Rathinavel, A.K., Radhakrishnan, P.: Altered glycosylation in cancer: A promising target for biomarkers and therapeutics. Biochim. Biophys. Acta. Rev. Cancer. 1875(1):188464 (2021). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi\u003c/span\u003e\u003cspan address=\"https://doi\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.bbcan.2020.188464\u003c/span\u003e\u003cspan address=\"10.1016/j.bbcan.2020.188464\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRadovani, B., Gudelj, I.: N-Glycosylation and Inflammation; the Not-So-Sweet Relation. Front. Immunol. 13: 893365 (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.frontiersin.org/articles/\u003c/span\u003e\u003cspan address=\"https://www.frontiersin.org/articles/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2022.893365/full\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2022.893365/full\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReily, C., Stewart, T.J., Renfrow, M.B., Novak, J.: Glycosylation in health and disease. Nat. Rev. Nephrol. 15(6): 346\u0026ndash;366 (2019). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.nature.com/articles/s41581-019-0129-4\u003c/span\u003e\u003cspan address=\"https://www.nature.com/articles/s41581-019-0129-4\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou, X., Motta, F., Selmi, C., Ridgway, W.M., Gershwin, M.E., Zhang, W.: Antibody Glycosylation in Autoimmune Diseases. Autoimmun. Rev. 20(5):102804 (2021). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.autrev.2021.102804\u003c/span\u003e\u003cspan address=\"10.1016/j.autrev.2021.102804\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGabius, H.J., Kaltner, H., Kopitz, J., Andr\u0026eacute;, S.: The glycobiology of the CD system: a dictionary for translating marker designations into glycan/lectin structure and function. Trends. Biochem. Sci. 40(7):360\u0026ndash;376 (2015). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.tibs.2015.03.013\u003c/span\u003e\u003cspan address=\"10.1016/j.tibs.2015.03.013\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ewww.functionalglycomics.\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003eorg/static/consortium/Nomenclature.shtml\u003c/span\u003e\u003cspan address=\"http://org/static/consortium/Nomenclature.shtml\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed 20 January 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchjoldager, K.T., Narimatsu, Y., Joshi, H.J., Clausen, H.: Global view of human protein glycosylation pathways and functions. Nat. Rev. Mol. Cell. Biol. 21(12):729\u0026ndash;749 (2020). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.nature.com/articles/s41580-020-00294-x\u003c/span\u003e\u003cspan address=\"https://www.nature.com/articles/s41580-020-00294-x\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVajaria, B.N., Patel, P.S.: Glycosylation: a hallmark of cancer?. Glycoconj. J. 34(2):147\u0026ndash;156 (2017). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://link.springer.com/article/10.1007/s\u003c/span\u003e\u003cspan address=\"https://link.springer.com/article/10.1007/s\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e10719-016-9755-2\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHollander, N., Haimovich, J.: Altered N-Linked Glycosylation in Follicular Lymphoma and Chronic Lymphocytic Leukemia: Involvement in Pathogenesis and Potential Therapeutic Targeting. Front. Immunol. 8:912 (2017). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.frontiersin.org/articles/\u003c/span\u003e\u003cspan address=\"https://www.frontiersin.org/articles/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2017.00912/full\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2017.00912/full\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBastian, K., Scott, E., Elliott, D.J., Munkley. J.: FUT8 Alpha-(1,6)-Fucosyltransferase in Cancer. Int. J. Mol. Sci. 22(1):455 (2021). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.mdpi.com/1422-0067/22/1/455\u003c/span\u003e\u003cspan address=\"https://www.mdpi.com/1422-0067/22/1/455\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBroekhuis, J.M., James, B.C., Cummings, R.D., Hasselgren, P.O.: Posttranslational Modifications in Thyroid Cancer: Implications for Pathogenesis, Diagnosis, Classification, and Treatment. Cancers (Basel). 14(7):1610 (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.mdpi.com\u003c/span\u003e\u003cspan address=\"https://www.mdpi.com\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e/2072-6694/14/7/1610\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGonz\u0026aacute;lez-C\u0026aacute;mpora, R., Sanchez Gallego, F., Martin Lacave, I., Mora Marin, J., Montero Linares, C., Galera-Davidson, H.: Lectin histochemistry of the thyroid gland. Cancer. 62(11):2354\u0026ndash;2362 (1988). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/1097-0142(19881201)62:11\u0026lt;2354::AID-CNCR2820621117\u0026gt;3.0.CO;2-D\u003c/span\u003e\u003cspan address=\"10.1002/1097-0142(19881201)62:11%3C2354::AID-CNCR2820621117%3E3.0.CO;2-D\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAudette, G.F., Olson, D.J.H., Ross, A.R.S., Quail, J.W., Delbaere, L.T.J.: Examination of the structural basis for O(H) blood group specificity by Ulex europaeus Lectin I. Canadian. J. Chem. 80(8) (2002). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1139/v02-134\u003c/span\u003e\u003cspan address=\"10.1139/v02-134\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGao, C., Hanes, M.S., Byrd-Leotis, L.A., Wei, M., Jia, N., Kardish, R.J., McKitrick, T.R., Steinhauer, D.A., Cummings, R.D.: Unique Binding Specificities of Proteins toward Isomeric Asparagine-Linked Glycans. Cell. Chem. Biol. 26(4):535\u0026ndash;547.e4 (2019). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi:10.1016/j.chembiol.2019.01.002\u003c/span\u003e\u003cspan address=\"https://doi:10.1016/j.chembiol.2019.01.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamashita, K., Ohkura, T., Umetsu, K., Suzuki, T.: Purification and characterization of a Fuc alpha 1\u0026ndash;\u0026gt;2Gal beta 1\u0026ndash;\u0026gt; and GalNAc beta 1\u0026ndash;\u0026gt;-specific lectin in root tubers of Trichosanthes japonica. J. Biol. Chem. 267(35):25414\u0026ndash;25422 (1992).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrete, A., Borges de Souza, P., Censi, S., Muzza, M., Nucci, N., Sponziello, M.: Update on Fundamental Mechanisms of Thyroid Cancer. Front. Endocrinol. (Lausanne). 11:102 (2020). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.frontiersin.org/articles/\u003c/span\u003e\u003cspan address=\"https://www.frontiersin.org/articles/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fendo.2020.00102/full\u003c/span\u003e\u003cspan address=\"10.3389/fendo.2020.00102/full\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBikas, A., Burman, K.D.: Epidemiology of thyroid cancer: a comprehensive guide for the clinician. In: The Thyroid and Its Diseases. 541\u0026ndash;547 (2019). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/978-3-319-72102-6_35\u003c/span\u003e\u003cspan address=\"10.1007/978-3-319-72102-6_35\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBasolo, F., Macerola, E., Poma, A.M., Torregrossa, L.: The 5th edition of WHO classification of tumors of endocrine organs: changes in the diagnosis of follicular-derived thyroid carcinoma. Endocrine. 80(3):470\u0026ndash;476 (2023). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://link.springer.com/article/\u003c/span\u003e\u003cspan address=\"https://link.springer.com/article/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12020-023-03336-4\u003c/span\u003e\u003cspan address=\"10.1007/s12020-023-03336-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaloch, Z.W., Asa, S.L., Barletta, J.A., Ghossein, R.A., Juhlin, C.C., Jung, C.K., LiVolsi, V.A., Papotti, M.G., Sobrinho-Sim\u0026otilde;es, M., Tallini, G., Mete, O.: Overview of the 2022 WHO Classification of Thyroid Neoplasms. Endocr. Pathol. 33(1):27\u0026ndash;63 (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://link.springer.com/article/\u003c/span\u003e\u003cspan address=\"https://link.springer.com/article/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12022-022-09707-3\u003c/span\u003e\u003cspan address=\"10.1007/s12022-022-09707-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKo\u0026ccedil;ak, \u0026Ouml;.F., Kayili, H.M., Albayrak, M., Yaman, M.E., Kadıoğlu, Y., Salih, B.: N-glycan profiling of papillary thyroid carcinoma tissues by MALDI-TOF-MS. Anal. Biochem. 584:113389 (2019). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ab.2019.113389\u003c/span\u003e\u003cspan address=\"10.1016/j.ab.2019.113389\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCao, Z., Zhang, Z., Liu, R., Wu, M., Li, Z., Xu, X., Liu, Z.: Serum Linkage-Specific Sialylation Changes Are Potential Biomarkers for Monitoring and Predicting the Recurrence of Papillary Thyroid Cancer Following Thyroidectomy. Front. Endocrinol (Lausanne). 13:858325 (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.frontiersin.org/articles/\u003c/span\u003e\u003cspan address=\"https://www.frontiersin.org/articles/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fendo.2022.858325/full\u003c/span\u003e\u003cspan address=\"10.3389/fendo.2022.858325/full\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang, Z., Reiding, K.R., Wu, J., Li, Z., Xu, X.: Distinguishing Benign and Malignant Thyroid Nodules and Identifying Lymph Node Metastasis in Papillary Thyroid Cancer by Plasma \u003cem\u003eN\u003c/em\u003e-Glycomics. Front. Endocrinol. (Lausanne). 12:692910 (2021). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.frontiersin.org/articles/\u003c/span\u003e\u003cspan address=\"https://www.frontiersin.org/articles/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fendo.2021.692910/full\u003c/span\u003e\u003cspan address=\"10.3389/fendo.2021.692910/full\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShimizu, K., Nakamura, K., Kobatake, S., Satomura, S., Maruyama, M., Kameko, F., Tajiri, J., Kato, R.: The clinical utility of Lens culinaris agglutinin-reactive thyroglobulin ratio in serum for distinguishing benign from malignant conditions of the thyroid. Clin. Chim. Acta. 379(1\u0026ndash;2):101\u0026ndash;104 (2007). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.cca.2006.12.017\u003c/span\u003e\u003cspan address=\"10.1016/j.cca.2006.12.017\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTarutani, O., Ui, N.: Properties of thyroglobulins from normal thyroid and thyroid tumor on a concanavalin A-sepharose column. J. Biochem. 98(3):851\u0026ndash;857 (1985). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/oxfordjournals.jbchem.a135344\u003c/span\u003e\u003cspan address=\"10.1093/oxfordjournals.jbchem.a135344\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZąbczyńska, M., Kozłowska, K., Pocheć, E.: Glycosylation in the Thyroid Gland: Vital Aspects of Glycoprotein Function in Thyrocyte Physiology and Thyroid Disorders. Int. J. Mol. Sci. 19(9):2792 (2018). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/ijms19092792\u003c/span\u003e\u003cspan address=\"10.3390/ijms19092792\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhan, X.X., Zhao, B., Diao, C., Cao, Y., Cheng, R.C.: Expression of MUC1 and CD176 (Thomsen-Friedenreich antigen) in Papillary Thyroid Carcinomas. Endocr. Pathol. 26(1):21\u0026ndash;26 (2015). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi-org.ezproxy.unal.edu.co/\u003c/span\u003e\u003cspan address=\"https://doi-org.ezproxy.unal.edu.co/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12022-015-9356-9\u003c/span\u003e\u003cspan address=\"10.1007/s12022-015-9356-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun, X., Tie, H.C., Chen, B., Lu, L.: Glycans function as a Golgi export signal to promote the constitutive exocytic trafficking. J. Biol. Chem. 295(43):14750\u0026ndash;14762 (2020). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.jbc.org/article/S0021-\u003c/span\u003e\u003cspan address=\"https://www.jbc.org/article/S0021-\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e9258(17)49351-3/fulltext\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLimaiem, F., Rehman, A., Anastasopoulou, C., Mazzoni, T.: Papillary Thyroid Carcinoma. [Updated 2023 Jan 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan\u0026ndash;. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/books/NBK536943/\u003c/span\u003e\u003cspan address=\"https://www.ncbi.nlm.nih.gov/books/NBK536943/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKamma, H., Kameyama, K., Kondo, T., Imamura, Y., Nakashima, M., Chiba, T., Hirokawa, M.: Pathological diagnosis of general rules for the description of thyroid cancer by Japanese Society of Thyroid Pathology and Japan Association of Endocrine Surgery. Endocr. J. 69(2):139\u0026ndash;154 (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.jstage.jst.go.jp/article/endocrj/69/2/69_EJ\u003c/span\u003e\u003cspan address=\"https://www.jstage.jst.go.jp/article/endocrj/69/2/69_EJ\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e21-0388/_article\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVowden, P., Lowe, A.D., Lennox, E.S., Bleehen NM.: Thyroid blood group isoantigen expression: a parallel with ABH isoantigen expression in the distal colon. Br. J. Cancer. 53(6):721\u0026ndash;725 (1986). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2001419/\u003c/span\u003e\u003cspan address=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2001419/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIto, N., Yokota, M., Nagaike, C., Morimura, Y., Hatake, K., Matsunaga, T.: Histochemical demonstration and analysis of poly-N-acetyllactosamine structures in normal and malignant human tissues. Histol. Histopathol. 11(1):203\u0026ndash;214 (1996).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIto, N., Yokota, M., Nagaike, C., Morimura, Y., Hatake, K., Tanaka, O., Matsunaga, T.: Simultaneous expression of keratan sulphate epitope (a sulphated poly-N-acetyllactosamine) and blood group ABH antigens in papillary carcinomas of the human thyroid gland. Histochem. J. 28(9):613\u0026ndash;623 (1996). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://link.springer.com/article/\u003c/span\u003e\u003cspan address=\"https://link.springer.com/article/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/BF02331382\u003c/span\u003e\u003cspan address=\"10.1007/BF02331382\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFonseca, E., Castanhas, S., Sobrinho-Simoes, M.: Expression of Simple Mucin Type Antigens and Lewis Type 1 and Type 2 Chain Antigens in the Thyroid Gland: An Immunohistochemical Study of Normal Thyroid Tissues, Benign Lesions, and Malignant Tumors. Endocr. Pathol. 7(4):291\u0026ndash;301 (1996). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://link.springer.com/article/\u003c/span\u003e\u003cspan address=\"https://link.springer.com/article/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/BF02739836\u003c/span\u003e\u003cspan address=\"10.1007/BF02739836\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIto, Y., Miyauchi, A., Yoshida, H., Uruno, T., Nakano, K., Takamura, Y., Miya, A., Kobayashi, K., Yokozawa, T., Matsuzuka, F., Taniguchi, N., Matsuura, N., Kuma, K., Miyoshi, E.: Expression of alpha1,6-fucosyltransferase (FUT8) in papillary carcinoma of the thyroid: its linkage to biological aggressiveness and anaplastic transformation. Cancer. Lett. 200(2):167\u0026ndash;172 (2003). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0304-3835(03)00383-5\u003c/span\u003e\u003cspan address=\"10.1016/s0304-3835(03)00383-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSancakli, A., Kaptan, E.: Lectin Treatment Affects Malignant Characteristics of TPC-1 Papillary Thyroid Cancer Cells. Eur. J. Biol. 78(1): 51\u0026ndash;57 (2019). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.26650/EurJBiol.2019.0006\u003c/span\u003e\u003cspan address=\"10.26650/EurJBiol.2019.0006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGonz\u0026aacute;lez-C\u0026aacute;mpora, R., Garc\u0026iacute;a-Sanatana, J.A., Jord\u0026agrave; i Heras, M.M., Salaverri, C.O., V\u0026aacute;zquez-Ram\u0026iacute;rez, F.J., Argueta-Manzano, O.E., Galera-Davidson, H.: Blood group antigens in differentiated thyroid neoplasms. Arch. Pathol. Lab. Med. 122(11):957\u0026ndash;965 (1998).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeng, Y., Zhan, X.X., Cao, Y., Zhang, H.W., Cao, W.H., Su, Y.J., Diao, C., Sun, Q.M., Cheng, R.C.: The Potential Action of Thomsen-Friedenreich Monoclonal Antibody (A78-G/A7) in Thyroid Cancer. Onco. Targets. Ther. 13:8677\u0026ndash;8689 (2020). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2147/OTT.S261685\u003c/span\u003e\u003cspan address=\"10.2147/OTT.S261685\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVijayakumar, T., Augustine, J., Mathew, L., Aleykutty, M.A., Nair, M.B., Remani, P., Nair, M.K.: Tissue binding pattern of plant lectins in benign and malignant lesions of thyroid. J. Exp. Pathol. 6(1\u0026ndash;2):11\u0026ndash;23 (1992).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSarker, A.B., Akagi, T., Teramoto, N., Nose, S., Yoshino, T., Kondo, E.: Bauhinia purpurea (BPA) binding to normal and neoplastic thyroid glands. Pathol. Res. Pract. 190(11):1005\u0026ndash;1011 (1994). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S0344-0338(11)80894-0\u003c/span\u003e\u003cspan address=\"10.1016/S0344-0338(11)80894-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVecchio, G., Parascandolo, A., Allocca, C., Ugolini, C., Basolo, F., Moracci, M., Strazzulli, A., Cobucci-Ponzano, B., Laukkanen, M.O., Castellone, M.D., Tsuchida, N.: Human a-L-fucosidase-1 attenuates the invasive properties of thyroid cancer. Oncotarget. 8(16):27075\u0026ndash;27092 (2017). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.18632/oncotarget.15635\u003c/span\u003e\u003cspan address=\"10.18632/oncotarget.15635\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaltner, H., Gabius, H.J.: Sensing Glycans as Biochemical Messages by Tissue Lectins: The Sugar Code at Work in Vascular Biology. Thromb. Haemost. 119(4):517\u0026ndash;533 (2019). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1055/s-0038-1676968\u003c/span\u003e\u003cspan address=\"10.1055/s-0038-1676968\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJung, J.Y., Oh, J.H., Lee, D.H., Lee, S., Chung, J.H.: Blood type B antigen modulates cell migration through regulating cdc42 expression and activity in HaCaT cells. J. Cell. Physiol. 228(11):2243\u0026ndash;2251 (2013). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/jcp.24393\u003c/span\u003e\u003cspan address=\"10.1002/jcp.24393\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsuchida, N., Ikeda, M.A., Ιshino, Υ., Grieco, M., Vecchio, G.: FUCA1 is induced by wild-type p53 and expressed at different levels in thyroid cancers depending on p53 status. Int. J. Oncol. 50(6):2043\u0026ndash;2048 (2017). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3892/ijo.2017.3968\u003c/span\u003e\u003cspan address=\"10.3892/ijo.2017.3968\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin, W.M., Karsten, U., Goletz, S., Cheng, R.C., Cao, Y.: Co-expression of CD173 (H2) and CD174 (Lewis Y) with CD44 suggests that fucosylated histo-blood group antigens are markers of breast cancer-initiating cells. Virchows. Arch. 456(4):403\u0026ndash;409 (2010). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00428-010-0897-5\u003c/span\u003e\u003cspan address=\"10.1007/s00428-010-0897-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHautala, L.C., Pang, P.C., Antonopoulos, A., Pasanen, A., Lee, C.L., Chiu, P.C.N., Yeung, W.S.B., Loukovaara, M., B\u0026uuml;tzow, R., Haslam, S.M., Dell, A., Koistinen, H.: Altered glycosylation of glycodelin in endometrial carcinoma. Lab. Invest. 100(7):1014\u0026ndash;1025 (2020). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41374-020-0411-x\u003c/span\u003e\u003cspan address=\"10.1038/s41374-020-0411-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLarena, A., Vierbuchen, M., Fischer, R.: Blood group antigen expression in malignant tumors of the thyroid: a parallel between medullary and nonmedullary carcinomas. Langenbecks. Arch. Chir. 380(5):269\u0026ndash;272 (1995). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/BF00184101\u003c/span\u003e\u003cspan address=\"10.1007/BF00184101\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS\u0026auml;lj\u0026ouml;, K., Thornell, A., Jin, C., Norl\u0026eacute;n, O., Teneberg, S.: Characterization of Human Medullary Thyroid Carcinoma Glycosphingolipids Identifies Potential Cancer Markers. Int. J. Mol. Sci. 22(19):10463 (2021). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.mdpi.com/\u003c/span\u003e\u003cspan address=\"https://www.mdpi.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e1422-0067/22/19/10463\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlanas, A., Sahasrabudhe, N.M., Rodriguez, E., van Kooyk, Y., van Vliet, S.J.: Fucosylated Antigens in Cancer: An Alliance toward Tumor Progression, Metastasis, and Resistance to Chemotherapy. Front. Oncol. 8, 39 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAdhikari, E., Liu, Q., Burton, C., Mockabee-Macias, A., Lester, D.K., Lau, E.: L-fucose, a sugary regulator of antitumor immunity and immunotherapies. Mol. Carcinog. 61(5):439\u0026ndash;453 (2022). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/mc.23394\u003c/span\u003e\u003cspan address=\"10.1002/mc.23394\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFu, J., Guo, Q., Feng, Y., Cheng, P., Wu, A.: Dual role of fucosidase in cancers and its clinical potential. J. Cancer. 13(10):3121\u0026ndash;3132 (2022). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7150/jca.75840\u003c/span\u003e\u003cspan address=\"10.7150/jca.75840\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLai, T.Y., Chen, I.J., Lin, R.J.,, G.S., Yeo, H.L., Ho, C.L., Wu, J.C., Chang, N.C., Lee, A.C., Yu, A.L.: Fucosyltransferase 1 and 2 play pivotal roles in breast cancer cells. Cell. Death. Discov. 5, 74 (2019). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41420-019-0145-y\u003c/span\u003e\u003cspan address=\"10.1038/s41420-019-0145-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeeley, T.S., Yang, S., Lau, E.: The Diverse Contributions of Fucose Linkages in Cancer. Cancers (Basel). 11(9):1241 (2019). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/cancers11091241]\u003c/span\u003e\u003cspan address=\"10.3390/cancers11091241]\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang, Z., Sun, P., Liu, J., Fu, L., Yan, J., Liu, Y., Yu, L., Wang, X., Yan, Q.: Suppression of FUT1/FUT4 expression by siRNA inhibits tumor growth. Biochim. Biophys. Acta. 1783(2):287\u0026ndash;296 (2008). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.bbamcr.2007.10.007\u003c/span\u003e\u003cspan address=\"10.1016/j.bbamcr.2007.10.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa, M., Fu, Y., Zhou, X., Guan, F., Wang, Y., Li, X.: Functional roles of fucosylated and O-glycosylated cadherins during carcinogenesis and metastasis. Cell. Signal. 63:109365 (2019). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.cellsig.2019.109365\u003c/span\u003e\u003cspan address=\"10.1016/j.cellsig.2019.109365\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYokota, M., Ito, N., Hirota, T., Yane, K., Tanaka, O., Miyahara, H., Matsunaga, T.: Histochemical differences of the lectin affinities of backbone polylactosamine structures carrying the ABO blood group antigens in papillary carcinoma and other types of thyroid neoplasm. Histochem. J. 27(2):139\u0026ndash;147 (1995). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/BF00243909\u003c/span\u003e\u003cspan address=\"10.1007/BF00243909\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVierbuchen, M., Schr\u0026ouml;der, S., Uhlenbruck, G., Ortmann, M., Fischer, R.: CA 50 and CA 19\u0026thinsp;\u0026ndash;\u0026thinsp;9 antigen expression in normal, hyperplastic, and neoplastic thyroid tissue. Lab. Invest. 60(5):726\u0026ndash;732 (1989).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVierbuchen, M., Larena, A., Schr\u0026ouml;der, S., Hanisch, F.G., Ortmann, M., Larena, A., Uhlenbruck, G., Fischer, R.: Blood group antigen expression in medullary carcinoma of the thyroid. An immunohistochemical study on the occurrence of type 1 chain-derived antigens. Virchows. Arch B Cell Pathol Incl Mol Pathol. 62(2):79\u0026ndash;88 (1992). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/BF02899668\u003c/span\u003e\u003cspan address=\"10.1007/BF02899668\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheng, S.P., Yang, P.S., Chien, M.N., Chen, M.J., Lee, J.J., Liu, CL.: Aberrant expression of tumor-associated carbohydrate antigen Globo H in thyroid carcinoma. J. Surg. Oncol. 114(7):853\u0026ndash;858 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIto, N., Yokota, M., Kawahara, S., Nagaike, C., Morimura, Y., Hirota, T., Matsunaga, T.: Histochemical demonstration of different types of poly-N-acetyllactosamine structures in human thyroid neoplasms using lectins and endo-beta-galactosidase digestion. Histochem. J. 27(8):620\u0026ndash;629 (1995).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhoury, E.L.: Reexpression of blood group ABH antigens on the surface of human thyroid cells in culture. J. Cell. Biol. 94(1):193\u0026ndash;200 (1982). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1083/jcb.94.1.193\u003c/span\u003e\u003cspan address=\"10.1083/jcb.94.1.193\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDogan, O.: Evaluation of ABO/Rh blood group distributions in papillary thyroid cancer patients. Medicine (Baltimore). 102(32):e34564 (2023). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MD.0000000000034564\u003c/span\u003e\u003cspan address=\"10.1097/MD.0000000000034564\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrewal, R.K., Shaikh, A.R., Gorle, S., Kaur, M., Videira, P.A., Cavallo, L., Chawla, M.: Structural Insights in Mammalian Sialyltransferases and Fucosyltransferases: We Have Come a Long Way, but It Is Still a Long Way Down. Molecules. 26(17):5203 (2021). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/molecules26175203\u003c/span\u003e\u003cspan address=\"10.3390/molecules26175203\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQin, H., Liu, J., Yu, M., Wang, H., Thomas, A.M., Li, S., Yan, Q., Wang, L.: FUT7 promotes the malignant transformation of follicular thyroid carcinoma through α-1,3-fucosylation of EGF receptor. Exp. Cell Res. 393:112095 (2020). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.yexcr.2020.112095\u003c/span\u003e\u003cspan address=\"10.1016/j.yexcr.2020.112095\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarsten, U., Goletz, S.: What controls the expression of the core-1 (Thomsen-Friedenreich) glycotope on tumor cells? Biochemistry (Mosc). 80(7):801\u0026ndash;807 (2015). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1134/S0006297915070019\u003c/span\u003e\u003cspan address=\"10.1134/S0006297915070019\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGlinskii, O.V., Sud, S., Mossine, V.V., Mawhinney, T.P., Anthony, D.C., Glinsky, G.V., Pienta, K.J., Glinsky, V.V.: Inhibition of prostate cancer bone metastasis by synthetic TF antigen mimic/galectin-3 inhibitor lactulose-L-leucine. Neoplasia. 14(1):65\u0026ndash;73 (2012). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1593/neo.111544\u003c/span\u003e\u003cspan address=\"10.1593/neo.111544\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaeland, E., Belo, A.I., Mongera, S., van Die, I., Meijer, G.A., van Kooyk, Y.: Differential glycosylation of MUC1 and CEACAM5 between normal mucosa and tumour tissue of colon cancer patients. Int. J. Cancer. 131(1):117\u0026ndash;128 (2012). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ijc.26354\u003c/span\u003e\u003cspan address=\"10.1002/ijc.26354\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYu, L.G., Andrews, N., Zhao, Q., McKean, D., Williams, J.F., Connor, L.J., Gerasimenko, O.V., Hilkens, J., Hirabayashi, J., Kasai, K., Rhodes, J.M.: Galectin-3 interaction with Thomsen-Friedenreich disaccharide on cancer-associated MUC1 causes increased cancer cell endothelial adhesion. J. Biol. Chem. 282(1):773\u0026ndash;781 (2007). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1074/jbc.M606862200\u003c/span\u003e\u003cspan address=\"10.1074/jbc.M606862200\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGlinsky, V.V., Glinsky, G.V., Rittenhouse-Olson, K., Huflejt, M.E., Glinskii, O.V., Deutscher, S.L., Quinn, TP.: The role of Thomsen-Friedenreich antigen in adhesion of human breast and prostate cancer cells to the endothelium. Cancer. Res. 61(12):4851\u0026ndash;4857 (2001).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeimburg, J., Yan, J., Morey, S., Glinskii, O.V., Huxley, V.H., Wild, L., Klick, R., Roy, R., Glinsky, V.V., Rittenhouse-Olson, K.: Inhibition of spontaneous breast cancer metastasis by anti-Thomsen-Friedenreich antigen monoclonal antibody JAA-F11. Neoplasia. 8(11): 939\u0026ndash;948 (2006). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1593/neo.06493\u003c/span\u003e\u003cspan address=\"10.1593/neo.06493\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChandler, K.B., Costello, C.E., Rahimi, N.: Glycosylation in the Tumor Microenvironment: Implications for Tumor Angiogenesis and Metastasis. Cells. 8(6):544 (2019). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/cells8060544\u003c/span\u003e\u003cspan address=\"10.3390/cells8060544\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCao, Y., Stosiek, P., Springer, G.F., Karsten, U.: Thomsen-Friedenreich-related carbohydrate antigens in normal adult human tissues: a systematic and comparative study. Histochem. Cell. Biol.106:197\u0026ndash;207 (1996).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVideira, P.A., Amado, I.F., Crespo, H.J., Alguer\u0026oacute;, M.C., Dall'Olio, F., Cabral, M.G., Trindade, H.: Surface alpha 2-3- and alpha 2-6-sialylation of human monocytes and derived dendritic cells and its influence on endocytosis. Glycoconj. J. 25(3):259\u0026ndash;268 (2008). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10719-007-9092-6\u003c/span\u003e\u003cspan address=\"10.1007/s10719-007-9092-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCid, E., Yamamoto, M., Yamamoto, F.: Mixed-Up Sugars: Glycosyltransferase Cross-Reactivity in Cancerous Tissues and Their Therapeutic Targeting. Chembiochem. 23(5):e202100460 (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/cbic.202100460\u003c/span\u003e\u003cspan address=\"10.1002/cbic.202100460\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKurtenkov, O.: Profiling of Naturally Occurring Antibodies to the Thomsen-Friedenreich Antigen in Health and Cancer: The Diversity and Clinical Potential. Biomed. Res. Int. 2020:9747040 (2020). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1155/2020/9747040\u003c/span\u003e\u003cspan address=\"10.1155/2020/9747040\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoffmann, M., Hayes, M.R., Pietruszka, J., Elling, L.: Synthesis of the Thomsen-Friedenreich-antigen (TF-antigen) and binding of Galectin-3 to TF-antigen presenting neo-glycoproteins. Glycoconj. J. 37(4):457\u0026ndash;470 (2020). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10719-020-09926-y\u003c/span\u003e\u003cspan address=\"10.1007/s10719-020-09926-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRenaud, F., Gnemmi, V., Devos, P., Aubert, S., Cr\u0026eacute;pin, M., Coppin, L., Ramdane, N., Bouchindhomme, B., d'Herbomez, M., Van Seuningen, I., Do Cao, C., Pattou, F., Carnaille, B., Pigny, P., W\u0026eacute;meau, J-L., Leteurtre, E.: Thyroid. 24(9):1375\u0026ndash;1384 (2014). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://doi.org/10.1089/thy.2013.0594\u003c/span\u003e\u003cspan address=\"10.1089/thy.2013.0594\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang, D.H., Jin, L., Xie, W.W., Lin, Q., Chen, X.: Clinicopathological significance of golgi phosphoprotein 3 expression in papillary thyroid carcinoma. Zhonghua. Yi. Xue. Za. Zhi. 99:2831\u0026ndash;2835 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu, R., Cao, Z., Wu, M. Li, X., Fan, P., Liu, Z.: Golgi-apparatus genes related signature for predicting the progression-free interval of patients with papillary thyroid carcinoma. BMC Med. Genomics. 16(1):60 (2023). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12920-023-01485-z\u003c/span\u003e\u003cspan address=\"10.1186/s12920-023-01485-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTopilko, A., Caillou, B.: Acetylcholinesterase and butyrylcholinesterase activities in human thyroid cancer cells. Cancer. 61:491\u0026ndash;499 (1988). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/1097-0142(19880201)61:3\u0026lt;491::AID-CNCR2820610314\u0026gt;3.0.CO;2-N\u003c/span\u003e\u003cspan address=\"10.1002/1097-0142(19880201)61:3%3C491::AID-CNCR2820610314%3E3.0.CO;2-N\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaini, S., Sripada, L., Tulla, K., Qiao, G., Kunda, N., Maker, A.V., Prabhakar, B.S.: MADD silencing enhances anti-tumor activity of TRAIL in anaplastic thyroid cancer. Endocr. Relat. Cancer. 26(6):551\u0026ndash;563 (2019). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1530/ERC-18-0517\u003c/span\u003e\u003cspan address=\"10.1530/ERC-18-0517\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu, J., Huang, Y., Li, T., Jiang, Z., Zeng, L., Hu, Z.: The role of the golgi apparatus in disease (review). Int. J. Mol. Med. 47:38 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePakdel, M., von Blume, J.: Exploring new routes for secretory protein export from the \u003cem\u003etrans\u003c/em\u003e-Golgi network. Mol. Biol. Cell. 29, 235\u0026ndash;240 (2018). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1091/mbc.E17-02-0117\u003c/span\u003e\u003cspan address=\"10.1091/mbc.E17-02-0117\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePolishchuk, E. V., Di Pentima, A., Luini, A., Polishchuk, R.S.: Mechanism of constitutive export from the Golgi: bulk flow via the formation, protrusion, and en bloc cleavage of large \u003cem\u003etrans\u003c/em\u003e-Golgi network tubular domains. Mol. Biol. Cell. 14, 4470\u0026ndash;4485 (2003). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1091/mbc.e03-01-0033\u003c/span\u003e\u003cspan address=\"10.1091/mbc.e03-01-0033\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKulkarni-Gosavi, P., Makhoul, C., Gleeson, P.A.: Form and function of the golgi apparatus: scaffolds, cytoskeleton and signalling. FEBS Lett. 593:2289\u0026ndash;2305 (2019). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/1873-3468.13567\u003c/span\u003e\u003cspan address=\"10.1002/1873-3468.13567\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRapoport, E.M., Ryzhov, I.M., Slivka, E.V., Korchagina, E.Y., Popova, I.S., Khaidukov, S.V., Andr\u0026eacute;, S., Kaltner, H., Gabius, H.J., Henry, S., Bovin, N.V.: Galectin-9 as a Potential Modulator of Lymphocyte Adhesion to Endothelium via Binding to Blood Group H Glycan. Biomolecules. 13(8):1166 (2023). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/biom13081166\u003c/span\u003e\u003cspan address=\"10.3390/biom13081166\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHerzog, B.H., Fu, J., Xia, L.: Mucin-type O-glycosylation is critical for vascular integrity. Glycobiology. 24(12):1237\u0026ndash;1241 (2014). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/glycob/cwu058\u003c/span\u003e\u003cspan address=\"10.1093/glycob/cwu058\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKayili, H.M., Salih, B.: Site-specific N-glycosylation analysis of human thyroid thyroglobulin by mass spectrometry-based Glyco-analytical strategies. J. Proteomics. 267:104700 (2022). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jprot.2022.104700\u003c/span\u003e\u003cspan address=\"10.1016/j.jprot.2022.104700\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eConte, M., Arcaro, A., D'Angelo, D., Gnata, A., Mamone, G., Ferranti, P., Formisano, S., Gentile, F.: A single chondroitin 6-sulfate oligosaccharide unit at Ser-2730 of human thyroglobulin enhances hormone formation and limits proteolytic accessibility at the carboxyl terminus. Potential insights into thyroid homeostasis and autoimmunity. J. Biol. Chem. 281(31):22200\u0026ndash;22211 (2006). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1074/jbc.M513382200\u003c/span\u003e\u003cspan address=\"10.1074/jbc.M513382200\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAntonelli, A., Ferrari, S.M., Corrado, A., Di Domenicantonio, A., Fallahi, P.: Autoimmune thyroid disorders. Autoimmun. Rev. 14(2):174\u0026ndash;180 (2015). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.autrev.2014.10.016\u003c/span\u003e\u003cspan address=\"10.1016/j.autrev.2014.10.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRalli, M., Angeletti, D., Fiore, M., D\u0026rsquo;Aguanno, V., Lambiase, A., Artico, M., de Vincentiis, M., Greco, A.: Hashimoto\u0026rsquo;s thyroiditis: an update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation. Autoimmun. Rev. 19(10):102649 (2020). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.autrev.2020.102649\u003c/span\u003e\u003cspan address=\"10.1016/j.autrev.2020.102649\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRenkonen, J., Tynninen, O., H\u0026auml;yry, P., Paavonen, T., Renkonen, R.: Glycosylation might provide endothelial zip codes for organ-specific leukocyte traffic into inflammatory sites. Am. J. Pathol. 161(2):543\u0026ndash;550 (2002). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0002-9440(10)64210-1\u003c/span\u003e\u003cspan address=\"10.1016/S0002-9440(10)64210-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTrzos, S., Link-Lenczowski, P., Sokołowski, G., Pocheć, E.: Changes of IgG N-Glycosylation in Thyroid Autoimmunity: The Modulatory Effect of Methimazole in Graves' Disease and the Association With the Severity of Inflammation in Hashimoto's Thyroiditis. Front. Immunol. 13:841710 (2022). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2022.841710\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2022.841710\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuo, E.J., Thi, W.J., Zheng, F., Zanocco, K.A., Livhits, M.J., Yeh, M.W.: Individualizing Surgery in Papillary Thyroid Carcinoma Based on a Detailed Sonographic Assessment of Extrathyroidal Extension. Thyroid. 27(12):1544\u0026ndash;1549 (2017). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1089/thy.2017.0457\u003c/span\u003e\u003cspan address=\"10.1089/thy.2017.0457\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaptan, E., Sancar-Bas, S., Sancakli, A., Bektas, S., Bolkent, S.: The effect of plant lectins on the survival and malignant behaviors of thyroid cancer cells. J. Cell. Biochem. 119(7):6274\u0026ndash;6287 (2018). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/jcb.26875\u003c/span\u003e\u003cspan address=\"10.1002/jcb.26875\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNozawa, Y., Ami, H., Suzuki, S., Tuchiya, A., Abe, R., Abe, M.: Distribution of sialic acid-dependent carbohydrate epitope in thyroid tumors: immunoreactivity of FB21 in paraffin-embedded tissue sections. Pathol. Int. 49(5):403\u0026ndash;407 (1999). doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1046/j.1440-1827.1999.00884.x\u003c/span\u003e\u003cspan address=\"10.1046/j.1440-1827.1999.00884.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJones, M., Oswald, D., Joshi, S., Whiteheart, S., Orlando, R., Cobb, B.: B-Cell-Independent Sialylation of IgG. Proc. Natl. Acad. Sci. USA. 113(26):7207\u0026ndash;7212 (2016). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1073/pnas.1523968113\u003c/span\u003e\u003cspan address=\"10.1073/pnas.1523968113\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Galatia lindenii lectin, diagnostic tool, glycotope, biomarker, hemagglutination","lastPublishedDoi":"10.21203/rs.3.rs-4406005/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4406005/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cem\u003eGalactia lindenii\u003c/em\u003e lectin type-II (GLL-II) belongs to the group of the legume lectins. The present study investigated the GLL-II staining patterns in histological sections of neoplastic and non-neoplastic thyroid tissues. Besides, hemagglutination assays (HA) using the GLL-II on red blood cells (RBCs) of different glycomic profile were performed, complementing previous results. The differential staining in Papillary Thyroid Cancer (PTC), Invasive Encapsulated Follicular Variant Papillary Thyroid Carcinoma (IEFV-PTC), Hashimoto's thyroiditis (HT), and non-neoplastic thyroid with goiter changes, together with the HA results and along with reviewed glycoprofiles of unhealthy conditions in other organs, allowed us to propose the potential utility of GLL-II in lectin platforms used to discriminate human pathological samples from normal ones. The present study shed light on potential applications of GLL-II in determining alterations of glycosylation patterns in specific cells, tissues, or body fluids, as well as glycotopes biomarkers of healthy or pathological conditions.\u003c/p\u003e","manuscriptTitle":"Galactia lindenii lectin type-II. Proposal of its potential use in diagnostic tools","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-22 10:38:33","doi":"10.21203/rs.3.rs-4406005/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"38541212-b2e6-4184-9c22-69fc7cb5f180","owner":[],"postedDate":"May 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-05T14:59:13+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-22 10:38:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4406005","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4406005","identity":"rs-4406005","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}