COLEC10 and COLEC11 are new serum biomarkers of chronic liver disease

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COLEC10 and COLEC11 are presumed to act as pattern recognition receptors to activate the complement system via binding to MASP1. A recent study has demonstrated that COLEC10 is predominantly produced by hepatic stellate cells and involved in the pathogenesis of liver fibrosis, which indicates the function of COLEC10 is beyond the pattern recognition receptors. However, it is not clear whether the serum concentrations of COLEC10 and COLEC11 can be diagnostic markers of chronic liver disease (CLD). Therefore, we designed a study quantifying the serum concentrations of COLEC10, COLEC11 and MASP1 in healthy donors and patients with chronic liver disease to investigate the correlation between the serum concentrations of COLEC10, COLEC11 and MASP1, and clinical liver disease markers. The results demonstrate that the serum concentrations of COLEC10 and COLEC11 are significantly increased in the patients with CLD. But the serum concentration of MASP1 didn’t show significant changes in CLD patients. The result of univariate correlation analysis reveals that the serum concentrations of COLEC10, COLEC11 and MASP1 are not strongly correlated with other clinical markers. Subgroup analysis based on the etiology of chronic liver disease demonstrates that the serum concentrations of COLEC10 and COLEC11 are increased in patients with viral hepatitis, autoimmune hepatitis and alcoholic hepatitis but not metabolic dysfunction-associated steatotic liver disease whereas MASP1 is only increased in patients with autoimmune hepatitis. Serum concentrations of COLEC10, COLEC11 and MASP1 are increased in patients with liver cirrhosis. In addition, the serum concentrations of COLEC10 and COLEC11 are increased in patients with stage B or C but the serum concentration of MAPS1 is only increased in patients with stage C. In summary, our study demonstrates that the serum concentrations of COLEC10 and COLEC11 are new biomarkers of chronic liver disease and MASP1 is a biomarker of liver cirrhosis. Further studies are needed to investigate the clinical value of serum concentrations of COLEC10 and COLEC11 in the diagnosis and prognosis of chronic liver disease. Health sciences/Biomarkers Health sciences/Gastroenterology/Hepatology Chronic Liver Disease Serum Marker Collectin Lectin Hepatic Stellate Cell Figures Figure 1 Figure 2 Figure 3 Introduction Various etiology including viruses, alcohol, metabolic dysfunction and et cetra, can induce liver injury and eventually lead to chronic liver disease (CLD) (1, 2). The hepatocyte function of albumin production, liver-specific coagulation factor production, and bile acid metabolism are impaired in chronic liver disease, which is represented by the reduction of serum albumin concentration, increase of prothrombin time and elevation of serum bile acids. Meanwhile, the necrotic hepatocytes release alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the serum concentration of both enzyme is increased (3). Currently, clinical diagnosis and treatment evaluation relies on the serum markers to monitor dynamic changes of liver function. In addition to hepatocyte injury, hepatic stellate cell activation also occurs in injured liver (4). The activated hepatic stellate cells produce excessive extracellular matrices which form the scar tissue in the fibrotic liver (5, 6). However, the activity of hepatic stellate cells can’t be accurately monitored by the commonly used serum markers. Currently common clinical serum markers, including ALT, AST and Child scoring related markers, mainly represent the function and damage of hepatocytes. Few markers can be used to monitor the activity of HSCs. Colletins are a few structural similar C-type lectins characterized by containing collage-like sequence and calcium dependent carbohydrate recognition domain. COLEC10 and COLEC11 are the members of soluble collectins, which are considered to function as pattern recognition molecule and binds to mannose binding lectin associated serine proteases 1 (MASP1) to activate the lectin pathway of complement activation (7). In addition, the mutation of COLEC10, COLEC11 and MASP1 is known to induce a kind of autosomal recessive disorder, 3MC syndrome (8). However, little is known about the role of COLEC10 and COLEC11 in chronic liver disease. In our previous study, we have demonstrated the COLEC10 is predominantly produced by hepatic stellate cells and involved in the pathogenesis of liver fibrosis (9). In addition, the serum concentration of COLEC10 is increased in patients with CLD (9). Therefore, we are wondering if the serum concentration of COLEC10 can be used as a diagnostic marker in chronic liver disease. COLEC11, also named CL-11, is an important paralog of COLEC10 that amino acid sequences, genomic organization, ubiquitous expression, and specific lectin activity of COLEC11 are in common with COLEC10 (10). However, the serum concentrations of COLEC10, COLEC11 and MASP1 are not fully investigated in patients with CLD. In this study, we collect serum from healthy donors and a cohort of patients with CLD to measure the serum concentrations of COLEC10, COLEC11 and MASP1 and investigate the diagnostic value of the markers for CLD. Methods Clinical Samples and Data The study included a cohort including 17 healthy donors and 128 patients who were diagnosed with chronic liver disease admitted to the Tianjin Medical University General Hospital. Patients with a history of consistent liver injury or elevated serum ALT or AST more than 6 months, voluntarily participated and signed the informed consent form were included. The patients complicated with multiple organ failure, pregnancy, malignancy, and liver transplantation history were excluded. The diagnosis of etiology of chronic liver disease is in accordance with current guidelines (11, 12). The demographic data of enrolled patients and healthy donors including age, gender, etiology of liver disease, cirrhosis or not, severity of liver disease in terms of Child-Pugh score was summarized in Table 1. The study was approved by the Ethics Committee of Tianjin General Hospital (Ethical NO. IRB2023-WZ-091). The samples and clinical data were collected with informed consent of the healthy donors and patients. The research was performed in accordance with the Declaration of Helsinki. Table 1. The demographic data CLD (N= 128 ) Ctrl (N= 17 ) Total (N=145) P Value Sex 0.9780468 a Male 48 (37.5%) 7 (41.2%) 55 (37.9%) Female 80 (62.5%) 10 (58.8%) 90 (62.1%) Age (years) 0.7725551 b Mean (SD) 59.2 (13.3) 61.0 (9.77) 59.4 (13.0) Median [Min, Max] 61.0 [22.0, 86.0] 65.0 [34.0, 71.0] 61.0 [22.0, 86.0] Etiology 1.546945e -29 a AH 16 (12.5%) - 16 (11.0%) AIH 28 (21.9%) - 28 (19.3%) MASLD 13 (10.2%) - 13 (9.0%) VH 14 (10.9%) - 14 (9.7%) Other 57 (44.5%) - 57 (39.3%) Ctrl - 17 (100%) 17 (11.7%) Cirrhosis 5.573249e -06 a Yes 79 (61.7%) - 79 (54.5%) No 49 (38.3%) 17 (100%) 66 (45.5%) ChildPugh 1.203447e -10 a A 26 (20.3%) 17 (100%) 43 (29.7%) B 41 (32.0%) - 41 (28.3%) C 61 (47.7%) - 61 (42.1%) COLEC10(pg/ml) 0.0003863283 b Median [Min, Max] 115 [35.8, 652] 65.1 [37.9, 1620] 113 [35.8, 1620] COLEC11(pg/ml) 0.01010969 b Median [Min, Max] 8620 [79.0, 31300] 4590 [377, 10500] 8090 [79.0, 31300] MASP1(pg/ml) 0.1548014 b Median [Min, Max] 9540 [794, 23500] 8060 [3960, 15400] 9330 [794, 23500] a ,The chi-square test (χ² test) was used for group comparisons. Count data were presented as the number of cases (percentage). b ,The Wilcoxon rank - sum test was used for group comparisons of numerical variables. Numerical variables were presented as Mean (SD) and Median [Min, Max]. Enzyme-Linked Immunosorbent Assay The serum concentrations of COLEC10, COLEC11 and MASP1 were measured with ELISA kits including Human Collectin-10(COLEC10) ELISA kit (CSB-EL005760HU, CUSABIO, China), Human Collectin-11(COLEC11) ELISA kit (JL14807-96T, JianglaiBio, China) and Human Mannose Associated Serine Protease 1 (MASP1) ELISA Kit (JL16890-96T, JianglaiBio, China). The procedure was performed following the manufacturer’s protocol. The blood samples were stored in EDTA tube and then centrifuged at 2-8 °C with 3000 rpm for 15 min and the supernatant was used for further analysis. The diluted serum samples and standard calibration samples were added into the pre-coated 96-well plates and then incubated at 37 °C for 1 h. After the solution was removed, the wells were washed with a washing solution. The enzyme conjugates were added to the wells with 50 μL per well except for the blank control wells and the plates were incubated at 37 °C for 30 min and then washed five times. The 100 μL TMB substrate solution was added into each well. After 10 min’s incubation, the reaction stop solution was added into each well and the plates were measured the optical density at 450 nm using SpectraMax i3x. Statistical Analysis Statistical significance of numerical variables was analyzed by Mann–Whitney test (Wilcoxon test) between the two groups and by Kruskal-Wallis test between the multiple groups. The chi-square test (χ² test) was used for comparison of categorical variables. The post-hoc analysis of the data was adjusted by Bonferroni correction. The correlation matrix was calculated with Pearson correlation analysis. ROC (Receiver Operating Characteristic) curve and AUC (Area Under Curve) and analysis of data was performed with R software (Version 4.3). p < 0.05 was considered statistically significant (*: p<0.05, **: p<0.01, ***: p<0.001, ****: p0.05). Results The serum concentrations of COLEC10, COLEC11 and MASP1 are increased in patients with CLD To investigate the serum concentrations of COLEC10, COLEC11 and MASP1 in patients with CLD, we measured theses protein with ELISA assay. The results revealed that the serum concentration of COLEC10 was elevated in the patients with CLD (65.1[37.9, 1620]pg/ml) compared to healthy donors (115 [35.8, 652]pg/ml) (p 0.001) (Fig.1A). Serum COLEC11 was also increased in patients (8620 [79.0, 31300]pg/ml) compared to donors (4590 [377, 10500]pg/ml)(p 0.05) (Fig.1B). However, the serum concentration of MASP1 did not increase in patients with CLD (9540 [794, 23500]pg/ml) compared to healthy donors (8060 [3960, 15400])(p 0.05) (Fig.1C). Then, we performed the univariate correlation test between the selected proteins including COLEC10, COLEC11 and MASP1 and common clinical characteristics and serum markers including age, blood cell counts, coagulation function, liver function and renal function (Fig.1D). According to the results, there was no mild or strong positive or negative correlation between COLEC10, COLEC11 and MASP1, which indicates the COLEC10 and COLEC11 were independently increased in the peripheral blood of patients with CLD. Interestingly, the serum concentration of COLEC11 showed weak to moderate negative correlation with the serum concentration of albumin (ALB) and moderate positive correlation with total bilirubin (Tbil) and direct bilirubin (Dbil), which indicated the serum concentration of COLEC11 was correlated with the deterioration of liver function. ROC curve and AUC were analyzed to evaluate the sensitivity and specificity of serum COLEC10, COLEC11 and MASP1 in CLD (Fig.1E). The results showed that COLEC10, COLEC11 and MASP1 had an AUC larger than 0.5. In addition, COLEC10 had the highest AUC, which suggests the COLEC10 had a better diagnostic performance than COLEC11 and MASP1. 2. COLEC10 and COLEC11 are elevated by various etiology of chronic liver disease. According to the diagnosis of patients with chronic liver disease, we performed subgroup analysis to investigate the serum concentration of COLEC10, COLEC11 and MASP1 among different etiologies of the chronic liver disease. The serum concentration of COLEC10 was elevated in all groups apart from the metabolic associated steatosis liver disease (MASLD) groups (Fig.2A). The serum concentration of COLEC11 was only elevated in patients with viral hepatitis (VH), autoimmune hepatitis (AIH) and alcoholic hepatitis (AH) (Fig.2B). Among the etiology of chronic liver disease, patients with VH had the highest median level of serum COLEC11. In contrast, the serum concentration of MASP1 was not elevated in most of the groups but only elevated a bit in AH group (Fig.2C). The results revealed that the serum concentrations of COLEC10 and COLEC11 were varied in different etiology of chronic liver disease. The cases were re-grouped by the cirrhosis state. The results showed that COLEC10, COLEC11 and MASP1 were significantly increased in the patients with cirrhosis (Fig.2D-F). 3. The serum concentration of COLEC10, COLEC11 and MASP1 is associated with liver function. In the previous results, the increase of serum concentrations of COLEC10 and COLEC11 varied by the etiology of chronic liver disease. We assumed the variation may be induced by the severity of chronic liver disease. Since the Child-Pugh stages were widely used to stratify the severity of patients with CLD, we were wondering if the increase of concentration was associated with the Child-Pugh scores. The whole cohort was classified into three groups based on their Child-Pugh scores. The results of subgroup analysis demonstrated that both COLEC10 and COLEC11 were significantly increased in Child C stages (p 0.001) (Fig.3A, B). However, the serum concentration of MASP1 was not increased between stage A group and stage B group (p 0.05) (Fig.3C). The results indicated that the increase of serum concentrations of COLEC10 and COLEC11 was in line with the severity of chronic liver disease. The results suggested serum concentrations of COLEC10 and COLEC11 were more sensitive than MASP1 to represent the deterioration of the chronic liver disease. Discussion Collectin subfamily member 10 (COLEC10), also named as CL-L1, is a member of C-type lectin family. The COLEC10 gene is located at 8q24.12 and the COLEC10 protein contains collagen-like sequences and carbohydrate recognition domain (13). COLEC11, also named CL-11, is an important paralog of COLEC10. COLEC11 and COLEC10 are proved to form homo- or hetero- hexamer and function as pattern recognition receptors in reaction to pathogens to activate lectin pathway of complement system (14). The current evidence demonstrates that the COLEC10 protein is predominantly in the adult liver (13). The COLEC10 was considered mainly to be expressed in hepatocytes (15). However, our previous work has demonstrated the COLEC10 is not produced by hepatocytes but by hepatic stellate cells and is involved in the pathogenesis of liver fibrosis (9). Interestingly, COLEC11 is a conserved marker of hepatic stellate cells of zebrafish, which suggests the hepatic stellate cells can produce COLEC11. In our previous results, we also find the mRNA of Colec11 is highly expressed in the hepatic stellate cells based on single-cell RNA sequencing (9). MASP1 has been reported to be secreted by hepatocytes and activates the haptic stellate cell to promote liver fibrosis (16). We are wondering if the serum concentration of COLEC10, COLEC11 and MASP1 is associated with the activity of hepatic stellate cells and possess the potential to be serum markers for the diagnosis of CLD. Therefore, we collect the serum samples of a cohort including healthy donors and patient with CLD to evaluate the diagnostic value of the serum concentrations of COLEC10, COLEC11 and MASP1. Although the mutations of COLEC10, COLEC11 and MASP1 are associated with 3MC syndrome, few studies measure the serum concentration of the three proteins in the patients with 3MC syndrome. MASP1/3 acts as an essential activator in the lectin pathway of complement activation (17). The serum concentrations of COLEC10 and COLEC11 in preterm are reported to range from 172 ng/ml to 1173 ng/ml and 78 ng/ml to 1306 ng/ml, respectively (18). The increased serum concentration of COLEC10 and COLEC11 has been reported to be associated with the long-term prognosis of kidney transplant recipient (19). The serum concentration of COLEC10 is increased in the patients with acute liver failure and cirrhosis (20). COLEC11 has different isoforms and COLEC11 and COLEC10 forms heterocomplexes in blood (21, 22), which suggests they may have complex post-translational modification. In our results, the serum concentration of COLEC10 and COLEC11 is significantly increased in the patients with CLD. A recent study also finds COLEC10 is a conserved hepatic stellate cell marker the serum concentration of COLEC10 is increased in the patients with liver fibrosis (23). COLEC11 is reported to be produced by extrahepatic cells (13, 24). But the concentration of COLEC11 in the patients of CLD is not comprehensively investigated. The serum concentration of MASP1 has no significant difference between CLD patients and healthy donors. The higher concentration of MASP1 is associated with worse prognosis of cervical cancer (25). However, few studies investigate the association between serum concentration of MAPS1 and CLD. No strong correlation is observed between COLEC10, COLEC11 and MASP1, and common clinical serum markers, which indicates the variation of the serum concentration of COLEC10 and COLEC11 is independent of the clinical serum markers, especially serum markers associated with hepatocyte injury. Although COLEC10 and COLEC11 are considered as paralogous genes, we have no idea why the correlation coefficient of their serum concentration is weak. Therefore, we assume the serum COLEC10 and COLEC11 are independent variables associated with the CLD. Furthermore, the subgroup analysis is performed to further evaluate the serum concentrations of COLEC10, COLEC11 and MASP1 in different etiologies of chronic liver disease. In the patients diagnosed with VH, AIH and AH, the serum concentrations of COLEC10 and COLEC11 are significantly increased. However, the serum concentrations of COLEC10 and COLEC11 are not altered in the patients with MASLD. MASLD can be diagnosed with common imaging techniques which indicate the accumulation of liver fat (26). The advanced liver fibrosis occurs in patients with MASH, which is the sever form of MASLD (2). Therefore, patients with MASLD may exhibit obvious hepatocyte steatosis but not liver fibrosis. Typical liver cirrhosis can be diagnosed with radiological images which indicate abnormal liver and spleen morphology with or without esophageal and/or gastric varices (27). MASP1 activity is increased in patients with hepatitis C virus induced severe liver fibrosis (28). Whereas few studies report the changes of COELC10 and COLEC11 in liver cirrhosis. Child-Pugh scoring system is widely used to evaluate the liver function of the patients with CLD (29). With the subgroup analysis based on the Child-Pugh stages, we find that the serum concentrations of COLEC10 and COLEC11 are higher in patients with severer Child stages. However, the serum concentration of MASP1 only shows significant increase in the patients with stage C. The reason may be most patients with stage C also complicated by liver cirrhosis. In summary, our study demonstrates that the serum COLEC10 and COLEC11 but not MASP1 are new independent biomarkers of the CLD. Increase of COLEC10 and COLEC11 is independently correlated with the deterioration of liver function. MASP1 can be a diagnostic marker for liver cirrhosis. More studies are needed to evaluate the diagnostic and prognostic value of the serum COLEC10 and COLEC11 in the CLD. Abbreviations Abbreviations Full Name WBC White Blood Cells RBC Red Blood Cells Hb Hemoglobin PLT Platelet NEUT Neutrophils LY Lymphocytes INR International Normalized Ratio PT Prothrombin Time ALB Albumin GLB Globulin ALT Alanine Aminotransferase AST Aspartate Transaminase GGT Gamma Glutamyltransferase Tbil Total Bilirubin Dbil Direct Bilirubin CREA Creatine UA Uric Acid CLD Chronic Liver Disease VH Viral Hepatitis AIH Autoimmune Hepatitis AH Alcoholic Hepatitis MASLD Metabolic Associated Steatosis Liver Disease COLEC10 Collectin Superfamily Number 10 COLEC11 Collectin Superfamily Number 11 MASP1 Mannose Associated Serine Protease 1 Declarations Conflict of interest The authors declare no conflict of interest. Data availability The data that support the findings of this study are provided in supplementary material. Author contribution MFZ designed the study. YJ and ZZ collected the sample and performed the ELISA assay. KL, MZW and SGJ performed the data analysis. MFZ, XCC and JZR reviewed the results, interpreted the data and wrote the manuscript. All authors reviewed the manuscript. Fundings The study is supported by the Department of Science and Technology of Henan Province (Grant No.24B320022) and the Health Commission of Henan Province (Grant No.LHGJ20210287). References Iwakiri Y, Trebicka J. Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy. JHEP Rep 2021;3:100316. Unagolla JM, Das S, Flanagan R, Oehler M, Menon JU. Targeting chronic liver diseases: Molecular markers, drug delivery strategies and future perspectives. International Journal of Pharmaceutics 2024;660. Thiele M, Pose E, Juanola A, Mellinger J, Gines P. Population screening for cirrhosis. Hepatol Commun 2024;8. Zhang M, Serna-Salas S, Damba T, Borghesan M, Demaria M, Moshage H. Hepatic stellate cell senescence in liver fibrosis: Characteristics, mechanisms and perspectives. Mech Ageing Dev 2021;199:111572. Tsuchida T, Friedman SL. 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Collectin-11 promotes cancer cell proliferation and tumor growth. JCI Insight 2023;8. Maestri CA, Nisihara R, Mendes HW, Jensenius J, Thiel S, Messias-Reason I, de Carvalho NS. MASP-1 and MASP-2 Serum Levels Are Associated With Worse Prognostic in Cervical Cancer Progression. Front Immunol 2018;9:2742. Parola M, Pinzani M. Liver fibrosis in NAFLD/NASH: from pathophysiology towards diagnostic and therapeutic strategies. Mol Aspects Med 2024;95:101231. Zhao H, Zhang X, Huang B, Shi X, Xiao L, Li Z. Application of machine learning methods for predicting esophageal variceal bleeding in patients with cirrhosis. Eur Radiol 2025;35:1440-1450. Brown KS, Keogh MJ, Tagiuri N, Grainge MJ, Presanis JS, Ryder SD, Irving WL, et al. Severe fibrosis in hepatitis C virus-infected patients is associated with increased activity of the mannan-binding lectin (MBL)/MBL-associated serine protease 1 (MASP-1) complex. Clin Exp Immunol 2007;147:90-98. Kok B, Abraldes JG. Child-Pugh Classification: Time to Abandon? Semin Liver Dis 2019;39:96-103. Additional Declarations No competing interests reported. Supplementary Files supplementarymaterial.pdf 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-5229457","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":443986196,"identity":"57201a17-1606-4a53-83a0-ab4458593e44","order_by":0,"name":"Mengfan Zhang","email":"","orcid":"","institution":"First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Mengfan","middleName":"","lastName":"Zhang","suffix":""},{"id":443986197,"identity":"a1f85197-aa98-40f8-8ac4-f43f1b3b8e93","order_by":1,"name":"Yang Jing","email":"","orcid":"","institution":"Tianjin Medical University General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Jing","suffix":""},{"id":443986198,"identity":"cbf4c723-46c0-4b21-b578-0aefff906800","order_by":2,"name":"Kun Li","email":"","orcid":"","institution":"First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Kun","middleName":"","lastName":"Li","suffix":""},{"id":443986200,"identity":"e688b107-50ad-48a1-b94a-9d4abb75a5e6","order_by":3,"name":"Manzhou Wang","email":"","orcid":"","institution":"First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Manzhou","middleName":"","lastName":"Wang","suffix":""},{"id":443986201,"identity":"f3d3ce23-fe24-4a22-8452-4c73ed253a5f","order_by":4,"name":"Shuguang Ju","email":"","orcid":"","institution":"First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Shuguang","middleName":"","lastName":"Ju","suffix":""},{"id":443986202,"identity":"d5078d96-ad82-4d0a-8d22-d30cbae1b094","order_by":5,"name":"Zhe Zhou","email":"","orcid":"","institution":"Tianjin Third Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhe","middleName":"","lastName":"Zhou","suffix":""},{"id":443986203,"identity":"c87248d1-92e3-40f7-8ccb-6da32f0e1b43","order_by":6,"name":"Xiaocang Cao","email":"","orcid":"","institution":"Tianjin Medical University General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiaocang","middleName":"","lastName":"Cao","suffix":""},{"id":443986204,"identity":"5af34f4f-f948-476f-abcf-7213169cb122","order_by":7,"name":"Jianzhuang Ren","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0UlEQVRIie3RsQrCMBCA4QuByxJ1PQffoVAoQoe+SrvYRZwdHAJCNuncN3GMFOpScXUVoXMdHRStOte4CeZfjkA+whEAl+sHE+o5EAavM/9MpHmTofqSAHjGmoiibs7rfuTvtzXBPEyU2JluIid+nlfIA2MmBFWaKDmLO0lEkvOeRgw2qiSmi0SR9LpfaclVo/SXTBO72RKmkTzkSEzZkMcubKXRo8c+47hMfS2nH4goTnDRZTTItsdDswhHmai6ybvyNWJof9WuheU9l8vl+svu1Ac4PQvYABsAAAAASUVORK5CYII=","orcid":"","institution":"First Affiliated Hospital of Zhengzhou University","correspondingAuthor":true,"prefix":"","firstName":"Jianzhuang","middleName":"","lastName":"Ren","suffix":""}],"badges":[],"createdAt":"2024-10-09 05:38:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5229457/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5229457/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":80997154,"identity":"a45ae175-5ec7-42a0-bc93-8e9bbcb636ec","added_by":"auto","created_at":"2025-04-21 05:34:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":8636281,"visible":true,"origin":"","legend":"\u003cp\u003eA-C The serum concentration of COLEC10, COLEC11 and MASP1 between healthy donors and patients with CLD. D The correlation matrix of serum markers of healthy donors and patients with CLD. E The ROC curve and AUC of COLEC10, COLEC11 and MASP1.\u003c/p\u003e","description":"","filename":"Figure100.png","url":"https://assets-eu.researchsquare.com/files/rs-5229457/v1/85d0e17f677b9bba781ee3c5.png"},{"id":80997158,"identity":"bc6eb5db-afb1-44e6-8949-4cdf7089bba8","added_by":"auto","created_at":"2025-04-21 05:34:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":10879468,"visible":true,"origin":"","legend":"\u003cp\u003eA-C The serum concentration of COLEC10, COLEC11 and MASP1 in different etiology of chronic liver disease. D-F The serum concentration of COLEC10, COLEC11 and MASP1 in all cases with or without liver cirrhosis.\u003c/p\u003e","description":"","filename":"Figure200.png","url":"https://assets-eu.researchsquare.com/files/rs-5229457/v1/9bb7779721b1503a09aaa3d4.png"},{"id":80997162,"identity":"4d215a48-36a6-4857-becf-167a47881fd5","added_by":"auto","created_at":"2025-04-21 05:34:32","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":3143029,"visible":true,"origin":"","legend":"\u003cp\u003eA-C The comparison of serum concentration of COLEC10, COLEC11 and MASP1 across different Child-Pugh stages in patients with CLD.\u003c/p\u003e","description":"","filename":"figure300.png","url":"https://assets-eu.researchsquare.com/files/rs-5229457/v1/df5798b208dc5a22ce0ade76.png"},{"id":82343071,"identity":"0a85f58e-1469-4181-b438-1827442f77fa","added_by":"auto","created_at":"2025-05-09 09:32:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":20042881,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5229457/v1/f907c056-11d8-46e2-a237-aa464d19a598.pdf"},{"id":80997157,"identity":"19cbc55c-9f2e-45a4-9e42-1b0ef46edef9","added_by":"auto","created_at":"2025-04-21 05:34:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":110266,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarymaterial.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5229457/v1/f6413ff431970d84a89f8223.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"COLEC10 and COLEC11 are new serum biomarkers of chronic liver disease","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVarious etiology including viruses, alcohol, metabolic dysfunction and et cetra, can induce liver injury and eventually lead to chronic liver disease (CLD) (1, 2). The hepatocyte function of albumin production, liver-specific coagulation factor production, and bile acid metabolism are impaired in chronic liver disease, which is represented by the reduction of serum albumin concentration, increase of prothrombin time and elevation of serum bile acids. Meanwhile, the necrotic hepatocytes release alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the serum concentration of both enzyme is increased (3). Currently, clinical diagnosis and treatment evaluation relies on the serum markers to monitor dynamic changes of liver function. In addition to hepatocyte injury, hepatic stellate cell activation also occurs in injured liver (4). The activated hepatic stellate cells produce excessive extracellular matrices which form the scar tissue in the fibrotic liver (5, 6). However, the activity of hepatic stellate cells can\u0026rsquo;t be accurately monitored by the commonly used serum markers. Currently common clinical serum markers, including ALT, AST and Child scoring related markers, mainly represent the function and damage of hepatocytes. Few markers can be used to monitor the activity of HSCs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eColletins are a few structural similar C-type lectins characterized by containing collage-like sequence and calcium dependent carbohydrate recognition domain. COLEC10 and COLEC11 are the members of soluble collectins, which are considered to function as pattern recognition molecule and binds to mannose binding lectin associated serine proteases 1 (MASP1) to activate the lectin pathway of complement activation (7). In addition, the mutation of COLEC10, COLEC11 and MASP1 is known to induce a kind of autosomal recessive disorder, 3MC syndrome (8). However, little is known about the role of COLEC10 and COLEC11 in chronic liver disease. In our previous study, we have demonstrated the COLEC10 is predominantly produced by hepatic stellate cells and involved in the pathogenesis of liver fibrosis (9). In addition, the serum concentration of COLEC10 is increased in patients with CLD (9). Therefore, we are wondering if the serum concentration of COLEC10 can be used as a diagnostic marker in chronic liver disease. COLEC11, also named CL-11, is an important paralog of COLEC10 that amino acid sequences, genomic organization, ubiquitous expression, and specific lectin activity of COLEC11 are in common with COLEC10 (10). However, the serum concentrations of COLEC10, COLEC11 and MASP1 are not fully investigated in patients with CLD.\u003c/p\u003e\n\u003cp\u003eIn this study, we collect serum from healthy\u0026nbsp;donors and a cohort of patients with CLD to measure the serum concentrations of COLEC10, COLEC11 and MASP1 and investigate the diagnostic value of the markers for CLD.\u003cbr\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eClinical Samples and Data\u003c/p\u003e\n\u003cp\u003eThe study included a cohort including 17 healthy donors and 128 patients who were diagnosed with chronic liver disease admitted to the Tianjin Medical University General Hospital. Patients with a history of consistent liver injury or elevated serum ALT or AST more than 6 months, voluntarily participated and signed the informed consent form were included. The patients complicated with multiple organ failure, pregnancy, malignancy, and liver transplantation history were excluded. The diagnosis of etiology of chronic liver disease is in accordance with current guidelines (11, 12). The demographic data of enrolled patients and healthy donors including age, gender, etiology of liver disease, cirrhosis or not, severity of liver disease in terms of Child-Pugh score was summarized in Table 1. The study was approved by the Ethics Committee of Tianjin General Hospital (Ethical NO. IRB2023-WZ-091). The samples and clinical data were collected with informed consent of the healthy donors and patients. The research was performed in accordance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003eTable 1. The demographic data\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"575\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCLD\u003cbr\u003e\u0026nbsp;(N=\u003c/strong\u003e\u003cstrong\u003e128\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCtrl\u003cbr\u003e\u0026nbsp;(N=\u003c/strong\u003e\u003cstrong\u003e17\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003cbr\u003e\u0026nbsp;(N=145)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eP Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e0.9780468\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e48 (37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e7 (41.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e55 (37.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e80 (62.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e10 (58.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e90 (62.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e0.7725551\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e59.2 (13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e61.0 (9.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e59.4 (13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eMedian [Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e61.0 [22.0, 86.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e65.0 [34.0, 71.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e61.0 [22.0, 86.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEtiology\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e1.546945e\u003csup\u003e-29\u003c/sup\u003e\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e16 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e16 (11.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eAIH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e28 (21.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e28 (19.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eMASLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e13 (10.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e13 (9.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eVH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e14 (10.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e14 (9.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e57 (44.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e57 (39.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eCtrl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e17 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e17 (11.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCirrhosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e5.573249e\u003csup\u003e-06\u003c/sup\u003e\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e79 (61.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e79 (54.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e49 (38.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e17 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e66 (45.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChildPugh\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e1.203447e\u003csup\u003e-10\u003c/sup\u003e\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e26 (20.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e17 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e43 (29.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e41 (32.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e41 (28.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e61 (47.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e61 (42.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCOLEC10(pg/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e0.0003863283\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eMedian [Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e115 [35.8, 652]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e65.1 [37.9, 1620]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e113 [35.8, 1620]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCOLEC11(pg/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e0.01010969\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eMedian [Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e8620 [79.0, 31300]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e4590 [377, 10500]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e8090 [79.0, 31300]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMASP1(pg/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e0.1548014\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eMedian [Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e9540 [794, 23500]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e8060 [3960, 15400]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e9330 [794, 23500]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e,The chi-square test (\u0026chi;\u0026sup2; test) was used for group comparisons. Count data were presented as the number of cases (percentage).\u003csup\u003eb\u003c/sup\u003e,The Wilcoxon rank - sum test was used for group comparisons of numerical variables. Numerical variables were presented as Mean (SD) and Median [Min, Max].\u003c/p\u003e\n\u003cp\u003eEnzyme-Linked Immunosorbent Assay\u003c/p\u003e\n\u003cp\u003eThe serum concentrations of COLEC10, COLEC11 and MASP1 were measured with ELISA kits including Human Collectin-10(COLEC10) ELISA kit (CSB-EL005760HU, CUSABIO, China), Human Collectin-11(COLEC11) ELISA kit (JL14807-96T, JianglaiBio, China) and Human Mannose Associated Serine Protease 1 (MASP1) ELISA Kit (JL16890-96T, JianglaiBio, China). The procedure was performed following the manufacturer\u0026rsquo;s protocol. The blood samples were stored in EDTA tube and then centrifuged at 2-8 \u0026deg;C with 3000 rpm for 15 min and the supernatant was used for further analysis. The diluted serum samples and standard calibration samples were added into the pre-coated 96-well plates and then incubated at 37 \u0026deg;C for 1 h. After the solution was removed, the wells were washed with a washing solution. The enzyme conjugates were added to the wells with 50 \u0026mu;L per well except for the blank control wells and the plates were incubated at 37 \u0026deg;C for 30 min and then washed five times. The 100 \u0026mu;L TMB substrate solution was added into each well. After 10 min\u0026rsquo;s incubation, the reaction stop solution was added into each well and the plates were measured the optical density at 450 nm using SpectraMax i3x.\u003c/p\u003e\n\u003cp\u003eStatistical Analysis\u003c/p\u003e\n\u003cp\u003eStatistical significance of numerical variables was analyzed by Mann\u0026ndash;Whitney test (Wilcoxon test) between the two groups and by Kruskal-Wallis test between the multiple groups. The chi-square test (\u0026chi;\u0026sup2; test) was used for comparison of categorical variables. The post-hoc analysis of the data was adjusted by Bonferroni correction. The correlation matrix was calculated with Pearson correlation analysis. ROC (Receiver Operating Characteristic) curve and AUC (Area Under Curve) and analysis of data was performed with R software (Version 4.3). p \u0026lt; 0.05 was considered statistically significant (*: p\u0026lt;0.05, **: p\u0026lt;0.01, ***: p\u0026lt;0.001, ****: p\u0026lt;0.001, ns: p\u0026gt;0.05).\u003c/p\u003e"},{"header":"Results","content":"\u003col\u003e\n \u003cli\u003eThe serum concentrations of COLEC10, COLEC11 and MASP1 are increased in patients with CLD\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eTo investigate the serum concentrations of COLEC10, COLEC11 and MASP1 in patients with CLD, we measured theses protein with ELISA assay. The results revealed that the serum concentration of COLEC10 was elevated in the patients with CLD (65.1[37.9, 1620]pg/ml) compared to healthy donors (115 [35.8, 652]pg/ml) (p\u003cimg width=\"11\" height=\"20\" src=\"https://myfiles.space/user_files/69519_bce2c0439cd956a6/69519_custom_files/img1744885490.png\" alt=\"image\"\u003e0.001)\u0026nbsp;(Fig.1A). Serum COLEC11 was also increased in patients (8620 [79.0, 31300]pg/ml) compared to donors (4590 [377, 10500]pg/ml)(p\u003cimg width=\"11\" height=\"20\" src=\"https://myfiles.space/user_files/69519_bce2c0439cd956a6/69519_custom_files/img174488549027.png\" alt=\"image\"\u003e0.05) (Fig.1B).\u0026nbsp;However, the serum concentration of MASP1 did not increase in patients with CLD (9540 [794, 23500]pg/ml) compared to healthy donors (8060 [3960, 15400])(p\u003cimg width=\"11\" height=\"20\" src=\"https://myfiles.space/user_files/69519_bce2c0439cd956a6/69519_custom_files/img174488549028.png\" alt=\"image\"\u003e0.05) (Fig.1C). Then, we performed the univariate correlation test between the selected proteins including COLEC10, COLEC11 and MASP1 and common clinical characteristics and serum markers including age, blood cell counts, coagulation function, liver function and renal function (Fig.1D). According to the results, there was no mild or strong positive or negative correlation between COLEC10, COLEC11 and MASP1, which indicates the COLEC10 and COLEC11 were independently increased in the peripheral blood of patients with CLD. Interestingly, the serum concentration of COLEC11 showed weak to moderate negative correlation with the serum concentration of albumin (ALB) and moderate positive correlation with total bilirubin (Tbil) and direct bilirubin (Dbil), which indicated the serum concentration of COLEC11 was correlated with the deterioration of liver function. ROC curve and AUC were analyzed to evaluate the sensitivity and specificity of serum COLEC10, COLEC11 and MASP1 in CLD (Fig.1E). The results showed that COLEC10, COLEC11 and MASP1 had an AUC larger than 0.5. In addition, COLEC10 had the highest AUC, which suggests the COLEC10 had a better diagnostic performance than COLEC11 and MASP1. \u003c/p\u003e\n\u003cp\u003e2. COLEC10 and COLEC11 are elevated by various etiology of chronic liver disease.\u003c/p\u003e\n\u003cp\u003eAccording to the diagnosis of patients with chronic liver disease, we performed subgroup analysis to investigate the serum concentration of COLEC10, COLEC11 and MASP1 among different etiologies of the chronic liver disease. The serum concentration of COLEC10 was elevated in all groups apart from the metabolic associated steatosis liver disease (MASLD) groups (Fig.2A). The serum concentration of COLEC11 was only elevated in patients with viral hepatitis (VH), autoimmune hepatitis (AIH) and alcoholic hepatitis (AH) (Fig.2B). Among the etiology of chronic liver disease, patients with VH had the highest median level of serum COLEC11. In contrast, the serum concentration of MASP1 was not elevated in most of the groups but only elevated a bit in AH group (Fig.2C). The results revealed that the serum concentrations of COLEC10 and COLEC11 were varied in different etiology of chronic liver disease. The cases were re-grouped by the cirrhosis state. The results showed that COLEC10, COLEC11 and MASP1 were significantly increased in the patients with cirrhosis (Fig.2D-F).\u003c/p\u003e\n\u003cp\u003e3. The serum concentration of COLEC10, COLEC11 and MASP1 is associated with liver function.\u003c/p\u003e\n\u003cp\u003eIn the previous results, the increase of serum concentrations of COLEC10 and COLEC11 varied by the etiology of chronic liver disease. We assumed the variation may be induced by the severity of chronic liver disease. Since the Child-Pugh stages were widely used to stratify the severity of patients with CLD, we were wondering if the increase of concentration was associated with the Child-Pugh scores. The whole cohort was classified into three groups based on their Child-Pugh scores. The results of subgroup analysis demonstrated that both COLEC10 and COLEC11 were significantly increased in Child C stages (p\u003cimg width=\"11\" height=\"20\" src=\"https://myfiles.space/user_files/69519_bce2c0439cd956a6/69519_custom_files/img174488549113.png\" alt=\"image\"\u003e0.001)\u0026nbsp;(Fig.3A, B). However, the serum concentration of MASP1 was not increased between stage A group and stage B group (p\u003cimg width=\"11\" height=\"20\" src=\"https://myfiles.space/user_files/69519_bce2c0439cd956a6/69519_custom_files/img174488549148.png\" alt=\"image\"\u003e0.05) (Fig.3C). The results indicated that the increase of serum concentrations of COLEC10 and COLEC11 was in line with the severity of chronic liver disease. The results suggested serum concentrations of COLEC10 and COLEC11 were more sensitive than MASP1 to represent the deterioration of the chronic liver disease.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCollectin subfamily member 10 (COLEC10), also named as CL-L1, is a member of C-type lectin family. The COLEC10 gene is located at 8q24.12 and the COLEC10 protein contains collagen-like sequences and carbohydrate recognition domain (13). COLEC11, also named CL-11, is an important paralog of COLEC10. COLEC11 and COLEC10 are proved to form homo- or hetero- hexamer and function as pattern recognition receptors in reaction to pathogens to activate lectin pathway of complement system (14). The current evidence demonstrates that the COLEC10 protein is predominantly in the adult liver (13). The COLEC10 was considered mainly to be expressed in hepatocytes (15). However, our previous work has demonstrated the COLEC10 is not produced by hepatocytes but by hepatic stellate cells and is involved in the pathogenesis of liver fibrosis (9). Interestingly, COLEC11 is a conserved marker of hepatic stellate cells of zebrafish, which suggests the hepatic stellate cells can produce COLEC11. In our previous results, we also find the mRNA of Colec11 is highly expressed in the hepatic stellate cells based on single-cell RNA sequencing (9). MASP1 has been reported to be secreted by hepatocytes and activates the haptic stellate cell to promote liver fibrosis (16). We are wondering if the serum concentration of COLEC10, COLEC11 and MASP1 is associated with the activity of hepatic stellate cells and possess the potential to be serum markers for the diagnosis of CLD. Therefore, we collect the serum samples of a cohort including healthy donors and patient with CLD to evaluate the diagnostic value of the serum concentrations of COLEC10, COLEC11 and MASP1.\u003c/p\u003e\n\u003cp\u003eAlthough the mutations of COLEC10, COLEC11 and MASP1 are associated with 3MC syndrome, few studies measure the serum concentration of the three proteins in the patients with 3MC syndrome. MASP1/3 acts as an essential activator in the lectin pathway of complement activation (17). The serum concentrations of COLEC10 and COLEC11 in preterm are reported to range from 172 ng/ml to 1173 ng/ml and 78 ng/ml to 1306 ng/ml, respectively (18).\u0026nbsp;The increased serum concentration of COLEC10 and COLEC11 has been reported to be associated with the long-term prognosis of kidney transplant recipient\u0026nbsp;(19). The serum concentration of COLEC10 is increased in the patients with acute liver failure and cirrhosis\u0026nbsp;(20). COLEC11 has different isoforms and COLEC11 and COLEC10 forms heterocomplexes in blood (21, 22), which suggests they may have complex post-translational modification.\u0026nbsp;In our results, the serum concentration of COLEC10 and COLEC11 is significantly increased in the patients with CLD. A recent study also finds COLEC10 is a conserved hepatic stellate cell marker the serum concentration of COLEC10 is increased in the patients with liver fibrosis (23). COLEC11 is reported to be produced by extrahepatic cells\u0026nbsp;(13, 24). But the concentration of COLEC11 in the patients of CLD is not comprehensively investigated. The serum concentration of MASP1 has no significant difference between CLD patients and healthy donors. The higher concentration of MASP1 is associated with worse prognosis of cervical cancer\u0026nbsp;(25). However, few studies investigate the association between serum concentration of MAPS1 and CLD.\u0026nbsp;No strong correlation is observed between COLEC10, COLEC11 and MASP1, and common clinical serum markers, which indicates the variation of the serum concentration of COLEC10 and COLEC11 is independent of the clinical serum markers, especially serum markers associated with hepatocyte injury. Although COLEC10 and COLEC11 are considered as paralogous genes, we have no idea why the correlation coefficient of their serum concentration is weak. Therefore, we assume the serum COLEC10 and COLEC11 are independent variables associated with the CLD.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurthermore, the subgroup analysis is performed to further evaluate the serum concentrations of COLEC10, COLEC11 and MASP1 in different etiologies of chronic liver disease. In the patients diagnosed with VH, AIH and AH, the serum concentrations of COLEC10 and COLEC11 are significantly increased. However, the serum concentrations of COLEC10 and COLEC11 are not altered in the patients with MASLD. MASLD can be diagnosed with common imaging techniques which indicate the accumulation of liver fat (26).\u0026nbsp;The advanced liver fibrosis occurs in patients with MASH, which is the sever form of MASLD\u0026nbsp;(2). Therefore, patients with MASLD may exhibit obvious hepatocyte steatosis but not liver fibrosis. Typical liver cirrhosis can be diagnosed with radiological images which indicate abnormal liver and spleen morphology with or without esophageal and/or gastric varices (27). MASP1 activity is increased in patients with hepatitis C virus induced severe liver fibrosis\u0026nbsp;(28). Whereas few studies report the changes of COELC10 and COLEC11 in liver cirrhosis.\u0026nbsp;Child-Pugh scoring system is widely used to evaluate the liver function of the patients with CLD\u0026nbsp;(29). With the subgroup analysis based on the Child-Pugh stages, we find that the serum concentrations of COLEC10 and COLEC11 are higher in patients with severer Child stages. However, the serum concentration of MASP1 only shows significant increase in the patients with stage C. The reason may be most patients with stage C also complicated by liver cirrhosis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn summary, our study demonstrates that the serum COLEC10 and COLEC11 but not MASP1 are new independent biomarkers of the CLD. Increase of COLEC10 and COLEC11 is independently correlated with the deterioration of liver function. MASP1 can be a diagnostic marker for liver cirrhosis. More studies are needed to evaluate the diagnostic and prognostic value of the serum COLEC10 and COLEC11 in the CLD.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eAbbreviations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eFull Name\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eWBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eWhite Blood Cells\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eRBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eRed Blood Cells\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eHb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eHemoglobin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003ePLT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003ePlatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eNEUT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eNeutrophils\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eLY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eLymphocytes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eINR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eInternational Normalized Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003ePT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eProthrombin Time\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eALB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eAlbumin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eGLB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eGlobulin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eALT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eAlanine Aminotransferase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eAST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eAspartate Transaminase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eGGT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eGamma Glutamyltransferase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eTbil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eTotal Bilirubin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eDbil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eDirect Bilirubin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eCREA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eCreatine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eUA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eUric Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eChronic Liver Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eVH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eViral Hepatitis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eAIH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eAutoimmune Hepatitis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eAlcoholic Hepatitis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eMASLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eMetabolic Associated Steatosis Liver Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eCOLEC10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eCollectin Superfamily Number 10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eCOLEC11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eCollectin Superfamily Number 11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eMASP1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 306px;\"\u003e\n \u003cp\u003eMannose Associated Serine Protease 1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003eConflict of interest\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003eData availability\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are provided in supplementary material.\u003c/p\u003e\n\u003cp\u003eAuthor contribution\u003c/p\u003e\n\u003cp\u003eMFZ designed the study. YJ and ZZ collected the sample and performed the ELISA assay. KL, MZW and SGJ performed the data analysis. MFZ, XCC and JZR reviewed the results, interpreted the data and wrote the manuscript.\u0026nbsp;All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003eFundings\u003c/p\u003e\n\u003cp\u003eThe study is supported by the Department of Science and Technology of Henan Province (Grant No.24B320022) and the Health Commission of Henan Province (Grant No.LHGJ20210287).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eIwakiri Y, Trebicka J. Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy. JHEP Rep 2021;3:100316.\u003c/li\u003e\n\u003cli\u003eUnagolla JM, Das S, Flanagan R, Oehler M, Menon JU. Targeting chronic liver diseases: Molecular markers, drug delivery strategies and future perspectives. International Journal of Pharmaceutics 2024;660.\u003c/li\u003e\n\u003cli\u003eThiele M, Pose E, Juanola A, Mellinger J, Gines P. 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JHEP Rep 2025;7:101223.\u003c/li\u003e\n\u003cli\u003eWang JX, Cao B, Ma N, Wu KY, Chen WB, Wu W, Dong X, et al. Collectin-11 promotes cancer cell proliferation and tumor growth. JCI Insight 2023;8.\u003c/li\u003e\n\u003cli\u003eMaestri CA, Nisihara R, Mendes HW, Jensenius J, Thiel S, Messias-Reason I, de Carvalho NS. MASP-1 and MASP-2 Serum Levels Are Associated With Worse Prognostic in Cervical Cancer Progression. Front Immunol 2018;9:2742.\u003c/li\u003e\n\u003cli\u003eParola M, Pinzani M. Liver fibrosis in NAFLD/NASH: from pathophysiology towards diagnostic and therapeutic strategies. Mol Aspects Med 2024;95:101231.\u003c/li\u003e\n\u003cli\u003eZhao H, Zhang X, Huang B, Shi X, Xiao L, Li Z. Application of machine learning methods for predicting esophageal variceal bleeding in patients with cirrhosis. Eur Radiol 2025;35:1440-1450.\u003c/li\u003e\n\u003cli\u003eBrown KS, Keogh MJ, Tagiuri N, Grainge MJ, Presanis JS, Ryder SD, Irving WL, et al. 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Semin Liver Dis 2019;39:96-103.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"Chronic Liver Disease, Serum Marker, Collectin, Lectin, Hepatic Stellate Cell","lastPublishedDoi":"10.21203/rs.3.rs-5229457/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5229457/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"COLEC10 and COLEC11 are soluble members of collectin super family. COLEC10 and COLEC11 are presumed to act as pattern recognition receptors to activate the complement system via binding to MASP1. A recent study has demonstrated that COLEC10 is predominantly produced by hepatic stellate cells and involved in the pathogenesis of liver fibrosis, which indicates the function of COLEC10 is beyond the pattern recognition receptors. However, it is not clear whether the serum concentrations of COLEC10 and COLEC11 can be diagnostic markers of chronic liver disease (CLD). Therefore, we designed a study quantifying the serum concentrations of COLEC10, COLEC11 and MASP1 in healthy donors and patients with chronic liver disease to investigate the correlation between the serum concentrations of COLEC10, COLEC11 and MASP1, and clinical liver disease markers. The results demonstrate that the serum concentrations of COLEC10 and COLEC11 are significantly increased in the patients with CLD. But the serum concentration of MASP1 didn’t show significant changes in CLD patients. The result of univariate correlation analysis reveals that the serum concentrations of COLEC10, COLEC11 and MASP1 are not strongly correlated with other clinical markers. Subgroup analysis based on the etiology of chronic liver disease demonstrates that the serum concentrations of COLEC10 and COLEC11 are increased in patients with viral hepatitis, autoimmune hepatitis and alcoholic hepatitis but not metabolic dysfunction-associated steatotic liver disease whereas MASP1 is only increased in patients with autoimmune hepatitis. Serum concentrations of COLEC10, COLEC11 and MASP1 are increased in patients with liver cirrhosis. In addition, the serum concentrations of COLEC10 and COLEC11 are increased in patients with stage B or C but the serum concentration of MAPS1 is only increased in patients with stage C. In summary, our study demonstrates that the serum concentrations of COLEC10 and COLEC11 are new biomarkers of chronic liver disease and MASP1 is a biomarker of liver cirrhosis. Further studies are needed to investigate the clinical value of serum concentrations of COLEC10 and COLEC11 in the diagnosis and prognosis of chronic liver disease.","manuscriptTitle":"COLEC10 and COLEC11 are new serum biomarkers of chronic liver disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-21 05:34:26","doi":"10.21203/rs.3.rs-5229457/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":"37aa989b-600e-4031-960e-2ffcde1aa133","owner":[],"postedDate":"April 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":47271635,"name":"Health sciences/Biomarkers"},{"id":47271636,"name":"Health sciences/Gastroenterology/Hepatology"}],"tags":[],"updatedAt":"2025-05-09T09:23:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-21 05:34:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5229457","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5229457","identity":"rs-5229457","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}