Expression of TCF7L2 in Glioma and Relation With Clinicopathological Characteristics and Patient Overall Survival

Expression of TCF7L2 in Glioma and Relation With Clinicopathological Characteristics and Patient Overall Survival | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Expression of TCF7L2 in Glioma and Relation With Clinicopathological Characteristics and Patient Overall Survival S.-Y. JING, L. CHEN, S. HAN, N. LIU, M.-Y. HAN, Y.-K. YANG, Chang-xiang Yan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-130738/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 Background: TCF7L2 gene is known as transcription factor 7-like 2 which has been identified as a novel transcription factor epithelial-mesenchymal transition (EMT) in tumor cells at 10q25.3. TCF7L2 may affect cancer progression and plays a central role in cancer proliferation, migration and invasion. However, its clinical and prognostic value have not been researched in glioma. The purpose of our study was to research TCF7L2 expression and evaluate the clinical value of prognosis. Method: We collected glioma specimens including low-grade glioma (n=46)and glioblastoma (n=51) from September 2015 to September 2017.Expression of TCF7L2 in 97 specimens were detected by quantitative real-time PCR (qRT-PCR).The chi-square test was applied to analyze the relationship between TCF7L2 expression and clinicopathological characteristics. The overall survival (OS) was analyzed by binary logistic regression analysis, the survival curves were drew by Kaplan-Meier. Univariate and multivariate analysis were utilized to analyze the relationship between prognosis and clinicopathological characteristics including TCF7L2 expression. RESULTS: Compared with low-grade glioma group, the expression of TCF7L2 was significantly increased (p<0.05). TCF7L2 overexpression was associated with large tumor volume (p=0.03), higher WHO grade (p=0.001), and recurrence (p=0.001). Moreover, Kaplan-Meier analysis proved that overexpressed TCF7L2 was related with poor OS (p< 0.05).The multivariate analysis suggested that TCF7L2 expression was an independent prognostic factor. CONCLUSIONS: Our research proved that TCF7L2 was over- expressed in glioblastoma, and, related with tumor prognosis, which, therefore, could be an independent prognostic factor for glioma patients. Neurology Neurosurgery Glioma TCF7L2 Overall Survival Prognosis clinicopathological characteristics Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Glioblastoma is the common malignant brain tumor owing to its stronger invasive ability and resistance to treatment. The morbidity rate of glioblastoma is approximate 0.59–0.69/100000 people worldwide, affecting those aged 20 years or older, especially those aged 40 to 70 years, with a median age of onset of 63 years 1 . The morbidity is higher in male (3.97/100000) than in females 2 , 3 (2.53/ 100000). According to NCCN Guidelines, the standard therapies include surgery, radiotherapy with concomitant temozolomide (TMZ), adjuvant TMZ chemotherapy and TTF therapies,but the 5-year OS is only 9.8% 3 . Although with comprehensive therapy,the median survival time is approximately 12–15 months for GBM patients after diagnosis 4 , 5 . Therefore,it is necessary to understand the mechanism of GBM and discuss its potential as a therapeutic target for GBM patients. The Wnt/β-catenin signaling pathway is important in majority tumor progression.TCF7L2 is a member of the Wnt/β-catenin signaling pathway,play an important role in metabolism, cell differentiation/ proliferation and cell death 6 .We collected the samples including 51 GBM tissues and 46 low-grade glioma tissues WHO(I-II).We focused on the TCF7L2 effect and the expression level in glioma tissue. Subsequently,we analyzed the relation between TCF7L2 expression level and clinicopathological characteristics,and investigated the prognosis factors. Method Patients and Tissue Samples Patients who were performed initial surgery in The Sanbo Brain Hospital of Capital Medical University from September 2015 to September 2017,were retrospectively selected for this research. All patients did not receive chemotherapy or radiotherapy prior to surgery. All samples were diagnosed by pathologists and stored in liquid nitrogen . The patients’ characteristics are described in Table I. Tissue samples usage was approved by Ethics Committee of the Sanbo Brain Hospital of Capital Medical University and written informed consent was obtained from all study participants. RNA Extraction and qRT-PCR Analyses The total RNA was extracted from the sample by using TRIzol reagent (Invitrogen, Carlsbad, CA, USA).RNA was reverse transcribed to complementary DNA (cDNA) by using a PrimeScript RT reagent kit (Thermo, Beijing, China). Its synthesis was conducted at 37 °C for 15 min, then 85 °C for 5 s according to the experimental protocols. Real-time PCR reactions were carried by Applied Biosystems 7500. Real-time PCRs was carried in triplicate.The relative TCF7L2 expression was computed and normalized using the 2- △ct method relative to GAPDH.The primers for TCF7L2:5’-TGCTCTGCGGTTGCTATGTTGAC-3’,3’-GCTGCGAGT CCTCACCAATGTC-5’and for GAPDH:5’-CAGACCACAGTCCATGC CATCAC-3’༌3’-GACGCCTGCTTCACCACCTTC-5’ Data Analysis The comparison of the TCF7L2 expression level between GBM and low-grade glioma was performed by the two-sample Student’s t-test. The chi-square test were used to examine the associations between TCF7L2 expression and the clinicopathological characteristics. In addition, survival curves were drew by the Kaplan-Meier method and analyzed with log-rank test. Cox proportional-hazards regression analysis was applied to estimate univariate and multivariate hazard ratios for OS. A value of P < 0.05 was considered as significantly different. SPSS software 20.0 was applied in the present study. Results TCF7L2 was Upregulated in Glioblastoma Tissues We measure TCF7L2 expression levels in 97 patients with glioma by the qRT-PCR. The data revealed that TCF7L2 had higher expression in GBM tissues than the low-grade group (p < 0.05, Fig. 1 ). Relation Between TCF7L2 Expression and Clinicopathological Factors of GBM Patients We found the TCF7L2 high expression in GBM.The median expression level of TCF7L2 was used as a dividing point.we divide 97 patients into two groups (high and low expression). Table I summarizes the relation between TCF7L2 expression and clinicopathological parameters in glioma.The results showed that TCF7L2 high expression was significantly related with larger tumor size (p = 0.03), higher WHO grade (p = 0.001) and recurrence (p = 0.001). Upregulation of TCF7L2 Confers Poor Prognosis in Patients Univariate and multivariate analysis were utilized to evaluate the association between OS and various clinicpathological features including TCF7L2 expression level (Table I). Kaplan-Meier method indicated that the five-year OS of patients was significantly shorter in patients with high TCF7L2 expression than in those with low TCF7L2 expression (p 0.05).The OS was significantly longer with small tumor size( ≦ 3 cm)compared to those with large tumor size(> 3 cm) (p < 0.05). The OS was significantly shorter in patients with recurrence than those with no recurrence (p < 0.05), but was significantly longer in patients with low grade group compared to those with glioblastoma (p 0.05) (Fig. 2 , 3 ). Multivariate analysis confirmed that TCF7L2 expression,WHO grade and recurrence was the independent prognostic factors for patients with glioma in five-year OS. Their hazard ratios were 4.91(95%CI,2.49–9.69),55.6 (95%CI,14.9-207.4),3.00(95%CI,1.31–6.86),respectively (p < 0.05) (Table II, Fig. 4 ). Table I. Relation of the expression level of TCF7L2 with clinicopathological parameters Table II. Univariate and multivariate analysis of 5-year OS. Parameter Univariate Multivariate HR 95% CI P HR 95% CI P Age (≤ 45/>45) 1.79 1 0.71–4.50 0.21 Sex (male/femal) 0.92 0.37–2.31 0.87 Tumor size (≤ 3 cm/>3 cm) 1.77 1.07–2.92 0.02 Necrosis (yes/no) 1.68 0.67–4.19 0.26 Recurrence (yes/no) 6.85 3.53–13.2 0.001 3.00 1.31–6.86 0.001 WHO grade (I-II/IV) 38.6 12.8-116.2 0.001 55.6 14.9-207.4 0.001 TCF7L2 expression (high/low) 1.83 1.12–2.98 0.01 4.91 2.49–9.69 0.001 Discussion TCF7L2 has been reported to have an effect on the surpression of cell proliferation, migration and invasion in the literature 7 .The transcription factor 7-like 2 (TCF7L2) gene may affect cancer development and prognosis because the TCF7L2 gene play an important role in the Wnt/ β -catenin signaling pathway 8 , 9 . To date, various biological markers have been reported in glioma 10 , 11 . TCF7L2, represents a central factor in metabolism, cell proliferation, and cell apoptosis 12 , 13 . Bo Yu 7 et al.found that TCF7L2 overexpression increased cell viability,migration and invasion in the cells with CRNDE inhibition.The TCF7L2 expression and prognostic value in glioma has not yet been reported. In our study, we detected significantly higher TCF7L2 expression in GBM tissues than in low-grade group. Moreover,TCF7L2 overexpression was significantly related with larger tumor size, higher WHO grade and necrosis. Our study reported shorter OS in patients with higher expression, however, there was no significant difference in 2-year OS in the two groups. We found that the 2-year OS was relatively high in the patients who underwent standard therapies including radiotherapy with concomitant temozolomide (TMZ), and adjuvant TMZ after surgery,in the high expression group. There was statistically significance in 5-year survival rate (p < 0.05). Multivariate analysis revealed that WHO grade, tumor recurrence and TCF7L2 expression level were independent prognositic factors for OS. The hazard ratio in high TCF7L2 expression group was 4.91 times more than low expression group(p < 0.05,95%CI,2.49–9.69).TCF7L2 expression was independently related with the OS, indicating that higher TCF7L2 level was a marker of poor prognosis for patients. Conclusions TCF7L2 could be a potential prognostic factor and therapeutic target for patients with glioma.The underlying molecular mechanisms of TCF7L2 involvement in the Wnt/β-catenin signaling pathway needs to be investigated in future studies. Abbreviations TCF7L2 Transcription factor 7-like 2 qRT-PCR Real-time quantitative PCR OS Overall survival TMZ Temozolomide EMT Epithelial-mesenchymal transition TTF Tumor Treating Fields GBM Gliomablastoma cDNA Complementary DNA HR Hazard ratios CI Confidence interval Declarations Ethics approval and consent to participate The experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of Capital Medical University Sanbo Brain Hospital. Written informed consent was obtained from individual or guardian participants. Consent to publish Not applicable. Availability of data and materials All data generated or analysed during this study are included in this published article. Competing interests The authors declare that they have no competing interests Funding Not applicable Authors' Contributions L. CHEN, S. HAN and N. LIU analyzed and interpreted the glioma patient data. S.-Y. JING performed the qRT-PCR of the glioma tissues, C.-X. YAN and S.-Y. JING were major contributors in writing the manuscript. All authors read and approved the final manuscript. Acknowledgements We appreciated W.-Y DENG for providing constructive suggestions to the manuscript. References Darlix A, Zouaoui S, Rigau V, Bessaoud F, Figarella Branger D, MathieuDaudé H, Trétarre B, Bauchet F, Duffau H,Taillandier L,Bauchet L.Epidemiology for primary brain tumors: a nationwide population-based study. J Neurooncol.2017; 131: 525-546. Ostrom QT,Gittleman H,Fulop J,Liu M,Blanda R,Kromer C,Wolinsky Y,Kruchko C, Barnholtz-Sloan JS.CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008-2012.Neuro Oncol.2015; 17: iv1-iv62. Koshy M,Villano JL,Dolecek TA,Howard A,Mahmood U,Chmura SJ, Weichselbaum RR,McCarthy BJ.Improved survival time trends for glioblastoma using the SEER 17 population-based registries. J Neuro-Oncol.2012; 107(1): 207-212. Stupp R,Hegi ME, Mason WP,Van den Bent MJ, Taphoorn MJB, Janzer RC, Ludwin SK,Allgeier A,Fisher B,Belanger K,Hau P,Brandes AA,Gijtenbeek J, Marosi C,Vecht CJ,Mokhtari K,Wesseling P,Villa S,Eisenhauer E,Gorlia T,Weller M, Lacombe D,Cairncross JG,Mirimanoff RO. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.Lancet Oncol.2009; 10: 459-466. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, Belanger K,Brandes AA,Marosi C,Bogdahn U,Curschmann J,Janzer RC,Ludwin SK,Gorlia T,Allgeier A,Lacombe D,Cairncross JG,Eisenhauer E,Mirimanoff RO. Radiotherapy plus concomitant and adjuvant Temozolomide for glioblastoma. N Engl J Med.2005; 352: 987-996. Hrckulak D, Kolar M, Strnad H, Korinek V.TCF/LEF Transcription Factors: An Update from the Internet Resources.Cancers (Basel) 2016; 8(7): 70. Yu B,Ye X,Du Q,Zhu B, Zhai Q, Li XX.The Long Non-Coding RNA CRNDE Promotes Colorectal Carcinoma Progression by Competitively Binding miR-217 with TCF7L2 and Enhancing the Wnt/β-Catenin Signaling Pathway.Cell Physiol Biochem 2017; 41: 2489-2502. Stefani Spranger, Riyue Bao, Thomas F Gajewski.Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity.Nature 2015; 523: 231-235. Zhao C, Deng Y, Liu L, Yu K, Zhang L, Wang H, He X, Wang J, Lu C, Wu LN, Weng Q, Mao M, Li J, van Es JH, Xin M, Parry L, Goldman SA, Clevers H, Lu QR.Dual regulatory switch through interactions of TCF712/TCF4 with stage-specific partners propels oligodendroglial maturation. Nat Commun 2016; 7: 10883. QU DW, XU HS, HAN XJ, WANG YL, OUYANG CJ. Expression of cyclinD1 and Ki-67 proteins in gliomas and its clinical significance.Eur Rev Med Pharmacol Sci 2014; 18: 516-519. LI W, XIE P, RUAN WH. Overexpression of LncRNA UCA1 promotes osteo- sarcoma progression and correlates with poor prognosis. J Bone Oncol 2016; 5: 80- 85. Chen C, Cao FQ, Bai LP,Liu Y, Xie JL,Wang W,Si Q,Yang J, Chang AT, Liu D, Liu DC,Chuang TH, Xiang R,Luo YP.IKKβ Enforces a LIN28B/TCF7L2 Positive Feedback Loop That Promotes Cancer Cell Stemness and Metastasis. Cancer Res 2015; 75(8): 1725-1735. Weng QJ, Tan BQ,Wang JJ,Wang J,Zhou H,Shi J,He QJ,Yang B.5-Fluorouracil causes severe CNS demyelination by disruption of TCF7L2/HDAC1/HDAC2 complex in adolescent mice.Toxicology 2014; 325: 144-150. 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-130738","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":6658425,"identity":"5b8b3288-668f-4251-bc07-8ea42c087f07","order_by":0,"name":"S.-Y. 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LIU","email":"","orcid":"","institution":"Capital Medical University Sanbo Brain Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"N.","middleName":"","lastName":"LIU","suffix":""},{"id":6658429,"identity":"7d9878b7-91ad-4fbf-b085-cc553ef72440","order_by":4,"name":"M.-Y. HAN","email":"","orcid":"","institution":"Capital Medical University Sanbo Brain Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"M.-Y.","middleName":"","lastName":"HAN","suffix":""},{"id":6658430,"identity":"00112d58-dda4-4cb7-83fb-221a59beab85","order_by":5,"name":"Y.-K. YANG","email":"","orcid":"","institution":"Capital Medical University Sanbo Brain Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Y.-K.","middleName":"","lastName":"YANG","suffix":""},{"id":6658431,"identity":"a61cec58-8b2a-48db-b429-f0a1f327b638","order_by":6,"name":"Chang-xiang Yan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7UlEQVRIiWNgGAWjYNCCCgk5Nvb2gw8+GNjYEaGcGYjPWBjz85xJNpxRkJZMnBbGlorEmTMczIR5PhxibCCkwZy9/+DjygYJxg03GNKYbQwOMDOwHz66AZ8Wy57DzIZnd0gwG9xuPPY4x+AOHwNPWtoNfFoMbiSzSTaekWAzuHMg3TjH4BkzgwSPGX4t9x+z/2xsk+AxuJFgJm1hcJixgaCWG8xsjEAtEpIzgFoYiNFi2ZNsLNlwRsIAHMg9BmnJbIT8Ys5+8OHHhoq6+jZQVP74Y2PHz374GH6HYYiw4VOOXcsoGAWjYBSMAnQAAFcpTKLh3sUTAAAAAElFTkSuQmCC","orcid":"","institution":"Capital Medical University Sanbo Brain Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Chang-xiang","middleName":"","lastName":"Yan","suffix":""}],"badges":[],"createdAt":"2020-12-17 13:58:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-130738/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-130738/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":4428531,"identity":"b0667843-a1b6-4165-988d-e3dbcb561a88","added_by":"auto","created_at":"2020-12-21 22:43:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":76535,"visible":true,"origin":"","legend":"Expression levels of TCF7L2 in GBM tissues were significantly higher (***p\u003c0.05).","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-130738/v1/8ec2746eb282d98745fdf986.png"},{"id":4428684,"identity":"e8ff6217-12b2-4d63-955c-31a3eb53c6eb","added_by":"auto","created_at":"2020-12-21 22:46:51","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":796155,"visible":true,"origin":"","legend":"Kaplan-Meier 5-year OS curves of patients with glioma according to clinicopathological features. A: TCF7L2 higher expression group showed shorter OS compared with patients with lower expression (p\u003c0.05),B: Patients with larger tumor size(\u003e3cm) showed worse OS compared with patients with small tumor size(≦3cm)(p\u003c0.05),C:Patients with necrosis showed no significantly differences compared with those with non-necrosis (p\u003e0.05), D:Patients with recurrence indicated worse OS compared with those with no recurrence(p\u003c0.05).","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-130738/v1/9616bc27e2a1bf7d514b5075.jpg"},{"id":4428683,"identity":"2cbd7132-dc5e-4f51-a081-bbf00fc7127c","added_by":"auto","created_at":"2020-12-21 22:46:51","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":910912,"visible":true,"origin":"","legend":"2 year OS curves of patients with glioma according to clinicopathological features A:Larger tumor size group(\u003e3cm) showed poor OS compared with small tumor size group(≦3cm) (p\u003c0.05), B:Patients with necrosis showed no significantly differences compared with those with no necrosis(p\u003e0.05), C: Patients with recurrence indicated worse OS compared with those with no recurrence(p\u003c0.05), D:Patients with higher expression of TCF7L2 showed no significantly differences compared with those with lower expression (p\u003e0.05).","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-130738/v1/2174f2dcc4118a1f269403f3.jpg"},{"id":4428533,"identity":"c6a47057-16bb-4036-8d00-0ed3dd923e39","added_by":"auto","created_at":"2020-12-21 22:43:51","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1825810,"visible":true,"origin":"","legend":"Forest plots analysis with 5-year OS with 95% confidence interval for clinicopathological features.","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-130738/v1/7fb942fc7cfcda74aac4613a.jpg"},{"id":13638917,"identity":"d746497f-1337-4735-a36f-964600ddcf11","added_by":"auto","created_at":"2021-09-17 08:52:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":566417,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-130738/v1/a908615a-6a73-47ee-a65d-8c3ecfd85642.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eExpression of TCF7L2 in Glioma and Relation With Clinicopathological Characteristics and Patient Overall Survival\u003c/p\u003e","fulltext":[{"header":"Background","content":" \u003cp\u003eGlioblastoma is the common malignant brain tumor owing to its stronger invasive ability and resistance to treatment. The morbidity rate of glioblastoma is approximate 0.59\u0026ndash;0.69/100000 people worldwide, affecting those aged 20\u0026nbsp;years or older, especially those aged 40 to 70\u0026nbsp;years, with a median age of onset of 63\u0026nbsp;years \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. The morbidity is higher in male (3.97/100000) than in females\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e (2.53/ 100000).\u003c/p\u003e \u003cp\u003eAccording to NCCN Guidelines, the standard therapies include surgery, radiotherapy with concomitant temozolomide (TMZ), adjuvant TMZ chemotherapy and TTF therapies,but the 5-year OS is only 9.8%\u003csup\u003e3\u003c/sup\u003e. Although with comprehensive therapy,the median survival time is approximately 12\u0026ndash;15\u0026nbsp;months for GBM patients after diagnosis\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Therefore,it is necessary to understand the mechanism of GBM and discuss its potential as a therapeutic target for GBM patients.\u003c/p\u003e \u003cp\u003eThe Wnt/β-catenin signaling pathway is important in majority tumor progression.TCF7L2 is a member of the Wnt/β-catenin signaling pathway,play an important role in metabolism, cell differentiation/ proliferation and cell death\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.We collected the samples including 51 GBM tissues and 46 low-grade glioma tissues WHO(I-II).We focused on the TCF7L2 effect and the expression level in glioma tissue. Subsequently,we analyzed the relation between TCF7L2 expression level and clinicopathological characteristics,and investigated the prognosis factors.\u003c/p\u003e "},{"header":"Method","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003ePatients and Tissue Samples\u003c/h2\u003e\n\u003cp\u003ePatients who were performed initial surgery in The Sanbo Brain Hospital of Capital Medical University from September 2015 to September 2017,were retrospectively selected for this research. All patients did not receive chemotherapy or radiotherapy prior to surgery. All samples were diagnosed by pathologists and stored in liquid nitrogen .\u003c/p\u003e\n\u003cp\u003eThe patients\u0026rsquo; characteristics are described in Table I. Tissue samples usage was approved by Ethics Committee of the Sanbo Brain Hospital of Capital Medical University and written informed consent was obtained from all study participants.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003eRNA Extraction and qRT-PCR Analyses\u003c/h2\u003e\n\u003cp\u003eThe total RNA was extracted from the sample by using TRIzol reagent (Invitrogen, Carlsbad, CA, USA).RNA was reverse transcribed to complementary DNA (cDNA) by using a PrimeScript RT reagent kit (Thermo, Beijing, China). Its synthesis was conducted at 37\u0026nbsp;\u0026deg;C for 15\u0026nbsp;min, then 85\u0026nbsp;\u0026deg;C for 5\u0026nbsp;s according to the experimental protocols. Real-time PCR reactions were carried by Applied Biosystems 7500. Real-time PCRs was carried in triplicate.The relative TCF7L2 expression was computed and normalized using the 2-\u003csup\u003e△ct\u003c/sup\u003e method relative to GAPDH.The primers for TCF7L2:5\u0026rsquo;-TGCTCTGCGGTTGCTATGTTGAC-3\u0026rsquo;,3\u0026rsquo;-GCTGCGAGT CCTCACCAATGTC-5\u0026rsquo;and for GAPDH:5\u0026rsquo;-CAGACCACAGTCCATGC CATCAC-3\u0026rsquo;༌3\u0026rsquo;-GACGCCTGCTTCACCACCTTC-5\u0026rsquo;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003eData Analysis\u003c/h2\u003e\n\u003cp\u003eThe comparison of the TCF7L2 expression level between GBM and low-grade glioma was performed by the two-sample Student\u0026rsquo;s t-test. The chi-square test were used to examine the associations between TCF7L2 expression and the clinicopathological characteristics.\u003c/p\u003e\n\u003cp\u003eIn addition, survival curves were drew by the Kaplan-Meier method and analyzed with log-rank test. Cox proportional-hazards regression analysis was applied to estimate univariate and multivariate hazard ratios for OS. A value of P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered as significantly different. SPSS software 20.0 was applied in the present study.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n\u003ch2\u003eTCF7L2 was Upregulated in Glioblastoma Tissues\u003c/h2\u003e\n\u003cp\u003eWe measure TCF7L2 expression levels in 97 patients with glioma by the qRT-PCR. The data revealed that TCF7L2 had higher expression in GBM tissues than the low-grade group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n\u003ch2\u003eRelation Between TCF7L2 Expression and Clinicopathological Factors of GBM Patients\u003c/h2\u003e\n\u003cp\u003eWe found the TCF7L2 high expression in GBM.The median expression level of TCF7L2 was used as a dividing point.we divide 97 patients into two groups (high and low expression). Table I summarizes the relation between TCF7L2 expression and clinicopathological parameters in glioma.The results showed that TCF7L2 high expression was significantly related with larger tumor size (p\u0026thinsp;=\u0026thinsp;0.03), higher WHO grade (p\u0026thinsp;=\u0026thinsp;0.001) and recurrence (p\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003eUpregulation of TCF7L2 Confers Poor Prognosis in Patients\u003c/h2\u003e\n\u003cp\u003eUnivariate and multivariate analysis were utilized to evaluate the association between OS and various clinicpathological features including TCF7L2 expression level (Table I).\u003c/p\u003e\n\u003cp\u003eKaplan-Meier method indicated that the five-year OS of patients was significantly shorter in patients with high TCF7L2 expression than in those with low TCF7L2 expression (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) ,but there were no significantly differences in two-year OS(p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).The OS was significantly longer with small tumor size(\u0026thinsp;≦\u0026thinsp;3\u0026nbsp;cm)compared to those with large tumor size(\u0026gt;\u0026thinsp;3\u0026nbsp;cm) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The OS was significantly shorter in patients with recurrence than those with no recurrence (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), but was significantly longer in patients with low grade group compared to those with glioblastoma (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). There were no significantly differences between necrosis and non-necrosis patients (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e,\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eMultivariate analysis confirmed that TCF7L2 expression,WHO grade and recurrence was the independent prognostic factors for patients with glioma in five-year OS. Their hazard ratios were 4.91(95%CI,2.49\u0026ndash;9.69),55.6 (95%CI,14.9-207.4),3.00(95%CI,1.31\u0026ndash;6.86),respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table II, Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable I.\u003c/strong\u003e Relation of the expression level of TCF7L2 with clinicopathological parameters\u003c/p\u003e\n\u003cp\u003e\u003cimg 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mzarg//VwMI/tEP9jGtUjzYzjjQzGkfyzh7HDiMhFZHHHCOo4BMexGEZuyaP9gjEaSd51Z7pnzK9rbfYjsZMnayR9BPxn/ZG40iesQSOTECRd2TrODYJXIxAHHScaaYX8dTzccoRUFWg4XRTlvQIhu6saT9p1KltkBdnPnL+lM24IiZyn3Gn/fSf9JSnz6uFcK9zjgiKOGPOSyKv2yB1014VebFdXS/pn7RwrnVHtiSNfmuI7em/95O8lE8/V7Rn5mh8TQKKvGva1VlJ4JAEqoOuA4yQ6/k45+RRnmt+ONuIA+pEBHRnTZ2kUT4Co4qROo56HcfeRUN39LTVBUTq9rK1/bNex0YRVswjtqhcq8ijTOp1m6Zu2qv5sV3sW9shLZxp+57AGGkjY0g/rLE6l/RzRXvew8065yGgyDuPrRypBE5PII4+zpQJkRaHWp1pBFmcP2Xj9ONsqyAgvzvrXidtpj/ybwkZVxcTtDdqazSOW/o5Q5nYsNol860suMY+EcA1r84zddNetWny+nqhDGlLdqnt53pk+2pP2qxjoO+E0TiSZyyBIxNQ5B3ZOo5NAhciwNsRHOnoV51thBzlujCIUw8W8mvdOPI46NynrQgU7lMmba3F6bf2RXnGGmFQ62cONe0K192G4d9tGlEU7uFXy8W2SaPtcCON69gvtqrtYAvaSH3y3gq1PPVqSF+kj+zcy9e6XkvgqARer/KjjtJxSUACEriRQJz/jcV3KYaYGIm/XTo7SaNdICKabhFm2vMkBnaYhySgyDukWRyUBCTwEQJ5K/SRNu6ti7ijf8MfAjDpb8dgxNuzW4L2vIWSZSTwNwFF3t9MTJGABC5AgLdpt7wp2nKq9Ee/htcE6p9CeYPHL3+CfV1y+U57LrMxRwJLBBR5S2RMl4AEJCABCUhAAicmoMg7sfEcugQkIAEJSEACElgioMhbImO6BCQgAQlIQAISODEBRd6JjefQJSABCUhAAhKQwBIBRd4SGdMlIAEJSEACEpDAiQko8k5sPIcuAQlIQAISkIAElggo8pbImC4BCUhAAhKQgAROTECRd2LjOXQJSEACEpCABCSwRECRt0TGdAlIQAISkIAEJHBiAoq8ExvPoUtAAhKQgAQkIIElAoq8JTKmS0ACEpCABCQggRMTUOSd2HgOXQISkIAEJCABCSwRUOQtkTFdAhKQgAQkIAEJnJiAIu/ExnPoEpCABCQgAQlIYImAIm+JjOkSkIAEJCABCUjgxAQUeSc2nkOXgAQkIAEJSEACSwQUeUtkTJeABCQgAQlIQAInJqDIO7HxHLoEJCABCUhAAhJYIqDIWyJjugQkIAEJSEACEjgxAUXeiY3n0CUgAQlIQAISkMASAUXeEhnTJSABCUhAAhKQwIkJKPJObDyHLgEJSEACEpCABJYIfFjkffr06eX79+9L7d+V/uXLl5efP3/eVffeSj9+/Hj5+vXrvdWtJwEJSEACEpDABgS+ffv2grbgtxbQCilXNQPXSX+rjbX2r5C3TvCNGSLuPn/+/ALorQLtbS0abx0bC2vLudzar+UkIAEJSEACEnj55f/jh3n5kuvOhpcy+GwCmqGKuaojKPfML3A+JPIAhxGAW1V0N8at9xgsRru1ztblmNOjRObWc7E9CUhAAhKQwJkIIOqqD0awoTN6IL3qjirsah00hSKv07vhHrgRZBVurUp6fWUaRV5fpSaNelUs0nbqUj51Uj7ikjLVgOSnXsaXupQjj7r1OuUYA2UZt0ECEpCABCQggbkE4qPTKz69ir6kr5XDp8ePJ069Z4vvfpMHdAQRAaARXwFIWsQXoqqCxjipSz3K9jK0Qx9pI/0QR7SlL9qmbG2jXtMfvywU6qdd6tJ/DaRlfDXdawlIQAISkIAE9iNQ9QG9LIk80uPHR+XI623tN+rjtny3yANwxFPiKowQVJQhILgoU69Thxhj1PK/Cv7vnwgu2o5II671ua5CjWvSqEugLvc1kJf8ms416YzZIAEJSEACEpDAPAL46qollkRe/Drl80s9/Dc6IVrhmf35a+Vzox0BGcGVKgijKrRIr0IwkIlH4or2IgrTJjFt5pf0pbIxOuVrP0lP/cRJr08D5CnyQshYAhKQgAQkMI9AF3X4Y3z1WsDnVz9ehSJ6YaQ51tq7Ut5dIq/CDAwgV5CA5TcKGIDyCbRXRVnSE1O+9hlxlva5p71q6Npeyqc97iMoua7jpswtiyptGUtAAhKQgAQksA0B/Hr8c71eah1tkPIpg2aIPriljdS7YvxukYcAAmAVRhFRpPNDYAE294kj7Hp57glL4gojxmAxAn2kXWJCbTfjxPgplzFTrqbXtslLufRlLAEJSEACEpDAHAL4/Pjt2iNp0RHx8bmv5Ub6oOY/0/W7Rd6tcBBOEW+pMzJG8ojJH5Wpb/Fq+T2u6b+Kvj36sE0JSEACEpCABCSwN4HdRB6Ku4o8rkcCrk+QN2xdZM0SefTbX/v28XkvAQlIQAISkIAEzkBgN5GHYMrrVuL3/AkUofXPP//8rj8DJK93Z4nJGfOxDwlIQAISkIAEnpvAbiLvubE6ewlIQAISkIAEJPBYAoq8x/K3dwlIQAISkIAEJLALAUXeLlhtVAISkIAEJCABCTyWgCLvsfztXQISkIAEJCABCexCQJG3C1YblYAEJCABCUhAAo8loMh7LH97l4AEJCABCUhAArsQUOTtgtVGJSABCUhAAhKQwGMJKPIey9/eJSABCUhAAhKQwC4EFHm7YLVRCUhAAhKQgAQk8FgCirzH8rd3CUhAAhKQgAQksAuBh4q80XdqSeMTYzXwubF8Is1Pj1UyXu9FgG8tr605PtOX/P6t5b3G9Mztxh79bIgNEns+XGeVYGvsWr+Bzuz4Brr2vo6dncm+BKaLvBzWbNJ+YOd7tzWd8jrRfReBrf9NgIeNhL5WWY/d8aSs8fYEls6Mfi5w39O2H40tziAQgddFXtIzhr43k24sAQn8S2CayOPwZUPyBmQp8BROfhV5OFvqVae7VN90CWxFoIq4vvZYj/x4o2CYRwDm9WyoNmIUvsWbZ4sZPUXcVztj/+pDur+YMS77kMCZCEwReTjDtw7g5PdNmw2Oo62b+0yQHet5CfBwsiQsEB1Zt+ed4XlG3kVeH3kX4z3f+3MRGIk8ZoAfwKewL91/57Kpo51PYIrIY1p5kxfRVqfKZs2fWbrIq+U4xFOupnstgT0IsN4QFvxG65Y+1/L2GNMzt7km8uoZ8syMrjT3JZHHHFkLivorWdu57EVgmsjLBBBxbNAq1urT2JrI4yD3T2QhaTyLAOu1rtHab94o1DSv9yGwJvKwz5IQ32c0tro3gSWRl72IyMNfGCQggWUC00VehsJG5dD+v//7v18x1/U3EnM+rYee8UwCPJDEsfR+WaeKi05ln/u3RN4+vdrqowiMRB57sb7B43rkKx41ZvuVwNEIPEzkLYFYe5PnU9sSNdP3JIAj4QGjB5xQdTg93/ttCSyJPN/wb8v5KK0tiTzWQQL7r/5VKOnGEpDAvwT+7JaDEKkiL5s8b/i4N0hgbwKIhqy5LixwKMnzoWNvS/xpP8y7PSjhn2r/cLrK1drZn78CsRaW3rBfhYPzkMBHCUwRebxOr4d0vfYp7KMmtL4EJCABCUhAAhL4m8AUkfd3t6ZIQAISkIAEJCABCexJQJG3J13bloAEJCABCUhAAg8ioMh7EHi7lYAEJCABCUhAAnsSUOTtSde2JSABCUhAAhKQwIMIKPIeBN5uJSABCUhAAhKQwJ4EFHl70rVtCUhAAhKQgAQk8CACirwHgbdbCUhAAhKQgAQksCcBRd6edG1bAhKQgAQkIAEJPIiAIu9B4O1WAhKQgAQkIAEJ7ElAkbcnXduWgAQkIAEJSEACDyKgyHsQeLuVgAQkIAEJSEACexI4nMjjO7f8avCj8JWG1zMJ/Pjx4/d3l9Pvly9ffqf57eVQ2S+uH6vvH6SvedpiPxvMbrnuu+4PPn/+/Hv/Uc4gAQksE5gi8jiY++E8GlIO7L6p+/2ormkS2JoAa/bTp08vrMsE1mIcSx4+an7KGW9HAFGdgD3Cn7RqH5y/tgipc8exeXxC7MqezDV7EfsbJCCBZQLTdkgcIgfxUogYrKIuG9nNvETN9D0IsF7X1mr6pEwVHUk33o5AnDotxvlzjY3qPWfFLQ+T243MlvYgUO1N+9XGvb8q8nue9xKQwMvLNJEX2GxgNmbfnBzYOEsO6SrysuEj9nKf9owlsAcBxBtrMWt1SchRzjW5hwX+bjNnRHLyUJj7LvqSbnxeApz7a/uL/WmQgASWCTx0h+AgOZgJeQLvIq8O3Sf1SsPrvQjgVHAeWZt5wOj9US7rtud5vy0B3uZEcMfp97NCkbct80e3hn+IzUdj4cGLvWmQgASWCTxE5MWJ1sM6Q+wHd9ITr726TxljCXyEAM4DB1MDzibrNekKvJCYF2OHcO9nhSJvnh1m9RRfMRJzWQezxmI/Ejgjgakij0OYQ3rkQPPElnhJzLmxz7jMzjXmOJY6atZlFXmsw6U/4dZ6Xm9LgDMkZ0AXdQiBkRjYdgS2NpvAyK74h7ofZ4/J/iRwFgJTRB6HMk4yh/MaHMosHdTk6VjX6Jm3FQGcSNbhSEyQlnDLuk5Z448RwC71DKjiu15/rBdrH4kALwWqoOt+wP13JGs5lqMRmCLy3jNpNmycK/Xqf5dRHet72rSsBO4hgGjgV988IzKSnth1eQ/d2+og6MKZuAo8Wqj52uE2pkcvhR2rzavAq/4gZfqaOPr8HJ8EZhI4nMibOXn7koAEJCABCUhAAlcloMi7qmWdlwQkIAEJSEACT01AkffU5nfyEpCABCQgAQlclYAi76qWdV4SkIAEJCABCTw1AUXeU5vfyUtAAhKQgAQkcFUCiryrWtZ5SUACEpCABCTw1AQUeU9tficvAQlIQAISkMBVCSjyrmpZ5yUBCUhAAhKQwFMTUOQ9tfmdvAQkIAEJSEACVyWgyLuqZZ2XBCQgAQlIQAJPTUCR99Tmd/ISkIAEJCABCVyVgCLvqpZ1XhKQgAQkIAEJPDWBu0Ve/TB4Phz+7du3zWDSFh+DN0hAAhKQgAQk8DwE8P/oCn5rAY2Qcj9//vxdtKaT//nz5995z3axTnCBxvfv33+BReglBGruPxJHQCryPkLRuhKQgAQkIIFzEUBfxPejBXLdZ/H169eXvFiKJqEMYq9qE+4p+6zhLpGHMgZqD1uC9E1ep+u9BCQgAQlI4NoEEHVVX/AWroq2zJ70+vaOe+rVNMqSNqqfdq4ev1vkAQyR10GOQGGs/ioV8RYFTl5V6bSZ8pSpedwnLwZjLJTBuOQZJCABCUhAAhI4LwF8eXw8s8DH4+t7uLVc1RG9jWe4f7cyyt/KKxwMEgEW8BFylMNAUdkpRzsRdWmLvIhHysc4EYaUS1+Ja520YywBCUhAAhKQwPkIdJ++JPJIR2ckLJWrZVL2meJ3i7y1N3kYJwo8b9dIyw+wVbBF5BHnrVzgUy4ijzhtJB7VSV1jCUhAAhKQgATORwAfn5c9jH5JvEU/RBP0etRFV/B75vBukRewI3UM5Crycl0B3yvyRobqwrD247UEJCABCUhAAuci0EUdL4yq6BvNpuqKmj/SKTX/Ga7fLfKAAlAEHXENVeQBF+MkBHY1RgQjcf78GmGYt3eUT39pi3vqKPJCxFgCEpCABCRwfgLVr9frpZmhLdALo7CUPip71bS7RB4wIsoQdvl1oBFqEYQYLGUj3HJPmzWNurU9DJmyXNf+IyCvaiTnJQEJSEACEngWAtXf1zlHS5CW/yQM3TAK6A1+zx7uFnnPDs75S0ACEpCABCQggSMTUOQd2TqOTQISkIAEJCABCdxJQJF3JzirSUACEpCABCQggSMTUOQd2TqOTQISkIAEJCABCdxJQJF3JzirSUACEpCABCQggSMTUOQd2TqOTQISkIAEJCABCdxJQJF3JzirSUACEpCABCQggZwDgnEAACAASURBVCMTUOQd2TqOTQISkIAEJCABCdxJQJF3JzirSUACEpCABCQggSMTUOQd2TqOTQISkIAEJCABCdxJQJF3JzirSUACEpCABCQggSMTeLjIy/do63dqK7D6jdq179D9/Pnz17dta12vJfBRAnX9pa2sNdbu2ppMeeOPEYDx0jlR85a+Yfmx3q39CAJ1343syrdNl3zGI8ZrnxI4KoGHizzAsFk5xHGePazl1bJxAjXNawl8hEA+kt3XZV2rfCS753+kT+u+JgBb7JAA+zh9hAD8E8hTdIfGueMIOOxf9xuzyr5MmXPP1NFLYF8ChxB5eSqrhznTzgHfN/kISQ6DUZ5pEngvAcRCFRCpT3p1LgiOvm5T1nh7ApU31xF89MR1tc32vdviDAKc5TWMbKqtKyGvJbBM4DAiL6/n6wZnI/f0iDmEXxV/Sc9Uc0+Z0SGRcsYSGBFA4OWNAWuIdUggrYq6LvpGbZm2HQHOBH4EbbEd16O2hK2rT8g4SfdcDw1jCSwTOIzIY4hs2hzg3HOIR6xlo5OWMvU65TLVKgB7uyljLIERgayl/OmP9cZ6ItQ1x70ib0Rwv7Tq2GEfu2iL/Zg/qmUetLBvtXHGosgLCWMJrBM4lMirhzbXvD2Jw43Iy3RyAETwpRz5efuXA4IY52yQwC0EWD/9T7WsIdaYIu8WgvuUyZlQW0f01X2e86CW8fq8BHKud7sq8s5rU0c+l8ChRB5Tx7mygbOps8mJCaSPHG7KUWbkpH9V9h8J3ECgrqUUz5pDaNS3SXWtpqzx9gTY02sPaiObbT8KW3wEgdEeI63uw0eMyz4lcAYChxN5eZtHTMjhTUxABHLgE+pblZT7lfHy8ksIchAkrDmIlDGWQAjgQLJ+urCL4KNsvU5d420JsLerQ8cuOQ/oifNAO2zL/EitceZXezM2Rd6RLORYjkzg4SKPwzm/bGTuCRF8yeeezZ17Nj/XtRxpBNpKOeK0/SvTfyRwA4Gsn6ypVImoyNpLuvH2BOrejj0i+HIWdPtsPwpbnEmg27yf3bE76yFrYeb47EsCZyLwcJF3JliOVQISkIAEJCABCZyFgCLvLJZynBKQgAQkIAEJSOAdBBR574BlUQlIQAISkIAEJHAWAoq8s1jKcUpAAhKQgAQkIIF3EFDkvQOWRSUgAQlIQAISkMBZCCjyzmIpxykBCUhAAhKQgATeQUCR9w5YFpWABCQgAQlIQAJnIaDIO4ulHKcEJCABCUhAAhJ4BwFF3jtgWVQCEpCABCQgAQmchYAi7yyWcpwSkIAEJCABCUjgHQSmiDy+G5tPEtV4xueI6K9/FucdfCz6pATqZ/H6d4/rGua65z8psl2nHXvku9XprH4Cy09chco14nw+sJ/f9bNm2N8gAQksE5gi8uiezdgP4b2dIyJSkbdsfHOWCdS1yhqKuOhOhfuettyqOfcQiMCrdqCdpEcEsN+1xT2Ej1cnAq+f39g3ezP2z9483iwckQQeT+ChIm/G9PshMaNP+zg/gQgHZhKnwnVN537vB5Xzk9xuBksiLz1gJ0VeaJw/joire479Vm3MvXvw/LZ2BvsReJjI6xuTA5pDvIoyXstTLq/nKZONX8uBJ3WJ65PdUrkZfyrez2y2PIsADqWup95vFYA9z/ttCfS9Tevw54zgXNAW2/J+dGs566vIw8b4g4T4iNwbS0ACrwlMFXlViFWRFyHH0HCq+bNLyrORs+Ejzupmrxu9XtNeFXnUjcOmzzqG11i8k8C/AiJrsDqasGEt1bcKSTfehwC2yP6tPbCvcy7UdK/PTSBnft17nO/V1v28P/eMHb0EticwVeTVJ+0qsNi0caaJmWrdwH3DV2EYLLRP/do299RN/bRPXMeTNowl0An0NZV81ll1QEk33ocAdugijzMCG2AL8g3XIZAzu++x7i980LqOzZ3J9gSmnYpsxCVRxabthzdTvVXk0XYcQK1DG6RzSOTA2B6hLV6dAOurPjhkvqO05BlvTyB7PC1zZtS3OthDm4TO+eOc2V3kZWbd/kk3loAE/hA4hMjjYO6HNUOsgq1veOqQT0A85mmu1iEvIo9r+qhOoF7/ash/JDAgwPrqDyHcZ/0Nqpi0A4GRyKv7u54JO3Rvk5MJ9DO/dp8H+5rmtQQk8DeBKSKPw5fDOL+/h/H6v3/CeWYTU4f71CWu7VGulkXIpU6uuU+o7XTHnTLGz02AdfHWOmENLr1heG56+8x+yR71bFj6S8E+I7LVPQlE4MXu2Ws5+7X1nvRt+0oE/qifK83KuUhAAhKQgAQkIIEnJ6DIe/IF4PQlIAEJSEACErgmAUXeNe3qrCQgAQlIQAISeHICirwnXwBOXwISkIAEJCCBaxJQ5F3Trs5KAhKQgAQkIIEnJ6DIe/IF4PQlIAEJSEACErgmAUXeNe3qrCQgAQlIQAISeHICirwnXwBOXwISkIAEJCCBaxJQ5F3Trs5KAhKQgAQkIIEnJ6DIe/IF4PQlIAEJSEACErgmAUXeNe3qrCQgAQlIQAISeHICirwnXwBOXwISkIAEJCCBaxL4S+Tlg9A95sPQRw2fP39+4aPyHwl88Dofwb63Her74ex76VlPAhKQwDUI4AfwoWv+4Pv377/KLJX79u3bC77tmQJ+PNpjzaevlUv9NfbPxPQvkRewLLAIO8RLrq8Ih43Ehtsi0M6zbcwtuNmGBCQggSsQwFfiPwnEua5z6z4VYVLLcU3aM/kSmDDnhHqdNOK1clXYbenXa/9nu/5DtI2cRXZlYZfpMs+6uZL+kXiPNj8yHutKQAISkMAcAogThAihC5KlEYz87bO9MOgMqliu3NbKhTvlqV/vaxvPdP0ukZdX0Lzty6vmKGfSUM71NSogSWPR1zdltUxV62kj/XQDpU/iKkDrpuK6/vIkVPtcqhvDZ8y13Sw4YtKJa5upm5gyBglIQAISeB4C8Ql1xtWP1PR6PXoxgJ+L/6plr3qN34dDQhdzSb+lHHaomiN1nzFeVCJLgFl0ACRQBuB5WmExc0+IUCIv5X5l/C8v1+RRtraR9lMmcdpGYOW69kM52iNks9Fu2k471GEBUIbrGmg3i4N++NEmc+OXen2uqZO2aGdpHiljLAEJSEAC1yEw8in4CnzQWog/q2XwKd0/1fyrXVffy9zwu/jfHt4qR534a33wy8smIg8j9MUdIUUeizWLmOtuOMqyCXob3bgxXt8wfRNF1MXA9BmjJ2YB1XGlL/JHgb67gEy5vuhIH6WlvLEEJCABCVyPwMiHdf/UZ40fiq+qeaQr8t4v8sIQdtEdSXvGeKxoVlQ04LIgET2B2Bc35VikhCqm6nWAU/YWkVfLUyehbyLyIsgoM+pzKb23lT4UeSFhLAEJSEACSwSqD8GvVV/V6+A3+0uPlMFvrdVNuavE+OzKgmsY9HBrOdhGn/Q2nun+LpEX8ABkQQP9VpHX37JxH0P0Nroh6oLnmrqEuqloqy4UxpY+M27uR2OmrVF90mmTOgTGSZ8J1EnbNY1yBglIQAISeB4C1VfU606g+j7y4qtSDp9SfV7SrxrHTzO/et3nW/PqdS8H++6Xe5lnuP+jVMpsES2IGH59kbEQk0c5fgFNetJSBtD1mm4ikkhP+72NMpzfl6O2qJ/269iSxnh6n+QlUJ++a0hdYhZJbbdeU5f2U76KutpHbdtrCUhAAhK4NoH4pfgfZhu/R4xfid9IXMvWfNp6llDnXf0pbJb4pFzVEDClLcPKf5P3LHAQbfy2DCyurdvccny2JQEJSEACEpDA9Qn8eaV1/bkuzpAnhK1UP08Vz/TktQjVDAlIQAISkIAEHkpAkfc//Ai9/mfb91qG+vWV8nvrW14CEpCABCQgAQlsRUCRtxVJ25GABCQgAQlIQAIHIqDIO5AxHIoEJCABCUhAAhLYioAibyuStiMBCUhAAhKQgAQORECRdyBjOBQJSEACEpCABCSwFQFF3lYkbUcCEpCABCQgAQkciIAi70DGcCgSkIAEJCABCUhgKwKKvK1I2o4EJCABCUhAAhI4EAFF3oGM4VAkIAEJSEACEpDAVgQUeVuRtB0JSEACEpCABCRwIAKKvAMZw6FIQAISkIAEJCCBrQg8VOTVb8byvddPnz753detLGs7mxH4+vXrr7XJ+qyfvvv27dvvdPJ6/mYDePKG+K50+PbPBmKP5G31/eknx32Y6fMd8NGeWtqPhxm4A5HAgQhMF3n1UGYTE9i0cZ4c4jhPgwSOQADhEPHAuqwiI+kZZ81LmvHHCHAucD4k4PTr+VBFAA+KOUdS3vicBCLwqn2Zydp+POdMHbUE9iUwTeSxOdmwHMQ91IOZAzzir5fzXgKzCdS1ybqsAqPmcV3zZo/zWfqDcUQfZ0oV1jXvWXhceZ7sqS7y6p7r+/HKLJybBO4lMEXk3Xr46ijvNaP1ZhCIuBj1xRr34WREZts0OPMjYI9qky76tu3Z1mYTGIm8OoZq+5rutQQk8IfAFJFHd3mTV5/E/gzj5dfBzVMbP8oaJHAUAoi3rM0lx7KUfpQ5XGUc9c0dzCP4mJ8i7ypW/nceSyLvlv14LRLORgL3E5gm8jLE/A8sloQch/joT7qpbyyBRxFAUPQ/HzEWnJEib3+rcGbUt6WKvP2ZP7KHJZGXMS3tx+QbS0ACLy/TRV6gc0CP3tqxsRV5oWR8NAKsTdZoDV181DyvtyGAuOtCur+5w+nXN3vb9GwrjyLwlshjXKP9+Kjx2q8EjkjgYSJvCYYH9RIZ0x9NAKFR/1yY8YzSkmf8cQI4+8qYMyJCu75Zrdcf79UWHk3gLZG3tB8fPW77l8CRCBxC5HE45+eT+JGWh2NBXGRtVqERMjii/oYpecYfJ8DbuvBPXO2Ao086ZQ3XIBCBF9tG1L+1H68xe2chge0ITBF5CLds1h57MG9nTFuSgAQkIAEJSEACITBF5KUzYwlIQAISkIAEJCCBOQQUeXM424sEJCABCUhAAhKYSkCRNxW3nUlAAhKQgAQkIIE5BBR5czjbiwQkIAEJSEACEphKQJE3FbedSUACEpCABCQggTkEFHlzONuLBCQgAQlIQAISmEpAkTcVt51JQAISkIAEJCCBOQQUeXM424sEJCABCUhAAhKYSkCRNxW3nUlAAhKQgAQkIIE5BBR5czjbiwQkIAEJSEACEphKQJE3FbedSUACEpCABCQggTkEDiPy+Mh7vmubj1HPQWAvElgm8OPHj9/rMqXqx9P99nKo7BfDOGcDH6ivoX4XG1sZrkGg7jtsnFD3XtZEzU85YwlI4F8CU0QeAo7fUuAQj7Nkw/aDfKme6RLYk0AePPpDB84laZ8/f/59vedYnrVtONezA/Zx6giBXHN+YAvDNQjEB0TUZb/FT2SW2F9xHxrGEvibwBSRR7dsTg7o0UGcDUy5enD/PVxTJDCHwJJoID0OiJHgZKoImTO65+2l8q7nBtfa4RrrotqVGdX91vO0+TVs7iz2IzBN5GUKbNK8Zu8bljJu2pAyfiQBHkZYi1mreVtAWl2jXfQ9cszP0Dcij18P1SY9z/vzEsDWIz/BjEjX7ue1rSOfQ2C6yKvTwpHiJAk40ThUN26l5PVsAnkQydrE0bA2CazNKjIUeXOtU9/q0HNshX163tyR2dvWBPAP8Qmjttl7efga5ZsmAQm8vDxE5OVgJu4hDnWU18t6L4E9COA4+n9WgLNhTSry9iB+W5trTp08bKTTv43lWUrFV9QHq4xdUR8SxhJYJjBV5OUg7g60D498RV6n4v0sAnEstb+IPNZwdS44n5EDqnW9/jgBxNtbb/ixiyLv46yP1sLSHntrPRxtHo5HAo8gMEXksRlxkrdsSg7p6kQfAcU+JcAajHjrwi6CD0r1Wmr7EEB01zMBu/SHQO7fenjcZ3S2ujeB0UM/e5KfQQISWCcwReStD+Hf//UUzpJfPczfqme+BPYkkDXZxQMPIsnT0expgT//q/zwrmdEHh5J6zbad1S2vicB9lS1dxf09K2f2NMCtn0lAocQeVcC6lwkIAEJSEACEpDAEQgo8o5gBccgAQlIQAISkIAENiagyNsYqM1JQAISkIAEJCCBIxBQ5B3BCo5BAhKQgAQkIAEJbExAkbcxUJuTgAQkIAEJSEACRyCgyDuCFRyDBCQgAQlIQAIS2JiAIm9joDYnAQlIQAISkIAEjkBAkXcEKzgGCUhAAhKQgAQksDEBRd7GQG1OAhKQgAQkIAEJHIGAIu8IVnAMEpCABCQgAQlIYGMCiryNgdqcBCQgAQlIQAISOAKBd4k8viGYbwr2bwfy7cjk8W3PRwT6H33n8BFjsU8JSEACEpCABG4nUL8L/paO4NvVXYfQ0xG0yO0z3r/ku0RehvPt27dfgo64BqAbJCABCUhAAhKQwHsI5CVS6vDSZimgNcjvIo/06JDv37//EnxLbTxL+jLFFQKIOwACuartwF2papYEJCABCUhAAhJ4RQBdUTUE1/1FUq1A3kjkpQ7ahLd6zx7uFnmobmBWtV0NBFgMQD6/+mfU+jo16dTlR9kYLvek1bbTL0ZMen8KSF3KxOjPbmznLwEJSEACEjgiAfx+9dVcx7+Pxkt+tELy8ffRG9Tl/tnDh0Qe8IAc0NUgXMdg9bUpZbknUCblMExV3ZRJfcqSl/v0R5w+qc+PgOBLeq33K9N/JCABCUhAAhI4FIGqDRgY/j5+fDRQ8qMFan7+yhidUfOe8frDIg9oiKtukPq2rgqwCLEOO2Iv6RivqnCuY1Di3k5/k0f//AwSkIAEJCABCRybAH69CrOuKfrol0QeWiJ6gDLPHjYReXlFWkUV11WkBTTiDAP0MBJ51eBV5KUubUX4xajJI07a2tNALe+1BCQgAQlIQALzCXRRh9+uGqCPaCTyqlCM/x/pjd7Wle83EXkAAnh9u4aBquiL0MIIuU49YtKq6ua61uc+Bq/p6TMGpS2uq/ir5ck3SEACEpCABCRwHALdh8e3L40QTRA/nzJVX9T2kv+M8btFHhCBzy+iK+BGwFO2CrikpQ3yklbbRPglvdavY0h6yiHoIvKSVtvMWI0lIAEJSEACEjgOAXx1/Hb9SyA+v+qLqhlqOjNJfeLaxnFmOXck7xZ5c4dnbxKQgAQkIAEJSEAC9xBQ5N1DzToSkIAEJCABCUjg4AQUeQc3kMOTgAQkIAEJSEAC9xBQ5N1DzToSkIAEJCABCUjg4AQUeQc3kMOTgAQkIAEJSEAC9xBQ5N1DzToSkIAEJCABCUjg4AQUeQc3kMOTgAQkIAEJSEAC9xBQ5N1DzToSkIAEJCABCUjg4AQUeQc3kMOTgAQkIAEJSEAC9xBQ5N1DzToSkIAEJCABCUjg4ASmiLz6CZL6qZGans+THZyXw3tCAqzZGupnc7iu32Ku5bzehkD91FH/hFF6oIx2CI3zx9U3dLvWz13yCUuDBCSwTOC191out0kO35Xt35FdOrQ36dBGJPBBAnEoaaavX+57Wsoaf5wATrw6eUT16IFQsf1x1kdpge+Nxsb5yHz2WN1vlNF/HMVqjuOoBKaKPDYvh3GevtiwfkD4qEvDccXZsGYTsnZzXwVI0oz3I4Bj78y5H6XvNwpbnkkg9qXPuv+yP2eOxb4kcDYCf7zXpJGzYfP01Q9rhsBhjVPll6e3PM1RflRn0tDt5skIsNay9pamnrW8lG/6tgQ4H/gl4Og5JxR5IXK9mH0YX1Bnpy+oNLyWwJjAdJEXp8mfbntgI8dpphxxnC359a1Kr++9BLYigGhg7WUdjtqNwBjlmbYPgZwPaT2OXpEXIteLu83Zd3kREPtfb9bOSALbEJgu8hj20oHMhs3mTRxHyv3oaW4bDLYigT8EEHasUcKayMvDx5+aXu1JgP3PeZAQIc790pmSssbnJFBt3GdAHn6BPWqQgATGBA4n8ti4SyEi0E29RMj0LQjEeeRBI3EVGPTjW4QtaN/WBuw7b/4aENskHv2F4LYeLHU0Aoj6NX/AeLG3/uBolnM8RyJwKJGXP8dm0+bJncM9DpZr0g0SmEGAtYiA6IH1+JYD6nW8v48ANqh/soN7zoi0SFoXgckzPh+BLupHtqVMXRfnm6UjlsD+BP72Xjv3yaZce+rmsE5+NjAbPPV8Ut/ZQDb/isCSyGNNdqHxqqI3mxDIg1/OBOKcC7UDRV6lce7r6gNi94i8+IGldXDumTt6CWxPYLrI234KtigBCUhAAhKQgAQk0Ako8joR7yUgAQlIQAISkMAFCCjyLmBEpyABCUhAAhKQgAQ6AUVeJ+K9BCQgAQlIQAISuAABRd4FjOgUJCABCUhAAhKQQCegyOtEvJeABCQgAQlIQAIXIKDIu4ARnYIEJCABCUhAAhLoBBR5nYj3EpCABCQgAQlI4AIEFHkXMKJTkIAEJCABCUhAAp2AIq8T8V4CEpCABCQgAQlcgIAi7wJGdAoSkIAEJCABCUigE5gi8vjebL5BWAfA9wiTzvcKDRI4EoH6Dc36vdR8z5a1y7dVDfsSqN+vrXag12ojPlhvuAaBatd8t5aZ1b2n77iGrZ3FvgSmiDymwAHMpuyHNAe4h/O+Rrb1+wgsPXiwjnE2BB5gcn1fL9ZaIwDb6uRhH7twbuSacwRbGM5PoNo1oi4PU4kzS+yv/wgNYwn8TWCqyGOD1kOa4ZDmJv3bMKY8lkDeMnfhwHqtDyo4mSpCHjvq6/deeVdx3cXg9Uk8zwzZXxHz1eYQcO89zzpwpvcRmC7yEHQIvQi7LvLYzOTzq870vulZSwL3EYgzidhLK9xXx9JFX8oZ70OA8yEOv/ZQbVLTvT4/AWzLPutBYd+JeC+BvwlMF3kMIUKO6yryEH71sEbk1fu/h2+KBPYnwBqMsKjX9KzI259/7aE/+OHofSishK533W2eGVbfkTRjCUjgNYGHiDyGwMblVzcqDpT7BA7w/uey5BlLYBaB+sZAkTeL+t/91LOi55JX/0LQ870/JwEerth/o7Ak/kZlTZPAsxJ4mMgDOIcyIi5/uu0OVJH3rMvyWPNmHeZNHmKiOhfSk3esUV9rNP0t/2h22CVnySjftHMRYK+t7S38hUECElgn8FCRx4Fcn77zNJ4hv7XJU85YAnsSQDzUtwms2dzX6z3H8Mxtw7oL6/APF+596x8a54+7qO+CDt/AzyABCawTmCLyeBrDGfLrm5W8+vS9VnZ9KuZKYDsCWa/EdX3SQx5OyNPRbMd81BJ8qy24juDjLEmeAm9E75xp1QfEvt1vZA2cc4aOWgLzCEwRefOmY08SkIAEJCABCUhAAhBQ5LkOJCABCUhAAhKQwAUJKPIuaFSnJAEJSEACEpCABBR5rgEJSEACEpCABCRwQQKKvAsa1SlJQAISkIAEJCABRZ5rQAISkIAEJCABCVyQgCLvgkZ1ShKQgAQkIAEJSECR5xqQgAQkIAEJSEACFySgyLugUZ2SBCQgAQlIQAISUOS5BiQgAQlIQAISkMAFCSjyLmhUpyQBCUhAAhKQgAQUea4BCUhAAhKQgAQkcEECirwLGtUpSUACEpCABCQgAUWea0ACEpCABCQgAQlckIAi74JGdUoSkIAEJCABCUhAkecakIAEJCABCUhAAhckoMi7oFGdkgQkIAEJSEACEni3yPv69evLp0+ffv1+/Pjx8uXLl9/33759+0WU9JT5z3/+8/uaNPIIySemzYSfP3++yvv8+XOypsTMJ/OY0qGdSEACEpDApQjELxLfEvCDo/D9+/dX/nFU5kppVTtEK4zmt1YuGmWkHeC5xHrUzxXSxivrjZkBEVgJI2GEEVImwi3lE1MvZUiLASifEIPlfs8YcccCUOTtSdm2JSABCVyXAD4rPoQ410szXvNx/SXIUhtXSO86YUmMrZWDNTwJ6Ilc5542l9q9AsPRHO4SeQi4Co/7rpprfjdKBtJFHvCr6KvlantJ3yMeCdY9+rFNCUhAAhK4HgH8WF5ULPm+zBrfiTAZCQ98XhUtqXPVuM818+/zXSuHDoFpQrUFaeSNWKf8FeO7RB4gqqjLQs7CJh9DJCQ/94mryAv82kbK0VbtL+nE5GG0+qMNxCLtUy9G5T7l6vjyBpGyXeSlftqofXstAQlIQAISCIH4sdwT4ztGfo08hMzIP9IOfgk/NesFRx3zI667712a+1K5cKys8d+wTBjZJ3lXje8WeSy8wMMYFXwWaKAFfgRWjfPmLkKrGij1aX8kstJuysWgMWTdXKSRT1i6Tnv0R2BOGV/m+CvDfyQgAQlIQAKNQPUtyap+KGnE+BR8TvxOzYuwo0yua/4Vr6u/DZ/R3JfKjThGE4RXtEHunyG+W+QhfmIAFmJd3NzXMIJPfjVW4FO2B9qLQOt5dQNRJqKMmPZ7oC3qpD3mUMdLndxTrv5Sp7fpvQQkIAEJSKD6wdCoPipp+Ln4me4fSY8f5Dp+NnWvGlc9wByX5r5UrnOkDXw2NkmIzsj9M8R3izzgALAu1izmvihH8KnfjUX9LPwKn3K9zeQj5iLEapku8jIG2q8bkTq1T/rKfeaTvowlIAEJSEACawSq38DvjF4O4GPit2oc31TTuB61sTaGM+bBpPpwrvPSps5nrVwXdbCrQZFXadxwHfHFQiZglJFhIrB6k13kRbBhiATa64ZKHjFtjEIXeXVhZCNRL5stbWRzUYa2a/uMxSABCUhAAhJYIoCfwK8Q6vVS+SX/SPnqt5bqXyW9cqjXfX41r153XiN2irxO8417INYnjBHACLcqnmg298RVPKWN5FeRNRpOyiWOks992s5iIJ0yxGmbOOW5zgalv5Qlf/RUMRqTaRKQgAQk8LwE4jfiYyAR30ZcQ3xTTcv1SKgk74px1QuVExwry6VyMKFc/HxlFP7x9TXvytev32WecKZVkDF8jM+mMUhAAhKQgAQkIIFnJnBqkTd6FZ43d89sVOcuAQlIQAISkIAETi3ymN/b8gAAEb9JREFUMF9evSaur3g1rwQkIAEJSEACEnhWAqcXec9qOOctAQlIQAISkIAE1ggo8tbomCcBCUhAAhKQgAROSkCRd1LDOWwJSEACEpCABCSwRkCRt0bHPAlIQAISkIAEJHBSAoq8kxrOYUtAAhKQgAQkIIE1Aoq8NTrmSUACEpCABCQggZMSUOSd1HAOWwISkIAEJCABCawRUOSt0TFPAhKQgAQkIAEJnJSAIu+khnPYEpCABCQgAQlIYI2AIm+NjnkSkIAEJCABCUjgpAQUeSc1nMOWgAQkIAEJSEACawQUeWt0zJOABCQgAQlIQAInJaDIO6nhHLYEJCABCUhAAhJYIzBF5H379u3l06dPv38/fvz4a0xfv379nU/Zf/7559U9bRgk8AgCrMdRyJolNuxH4OfPn7/Pgs66ni2jc2W/Udny3gSwJ3sP+9eQfTfKq+W8loAEXl7G3msHMtmwa01///795fPnz6+KsJE9vF8h8WYigTiU3iXr8suXLz3Z+x0IVM71POBcyMPf6OzYYSg2OYlA/EUXctiZHwHb17UxaWh2I4FTEVDkncpcDnYmgYgIHE0NOJaIi5ru9T4E6puc6tRrOtf9Ld8+o7HVWQSwaRd51ebZn7PGYz8SOCOB195rxxnkyWyti9HTeH1yX6trngS2JoBoiKNJ21nHecPX3zynnPH2BDgf4D8KCrwRlXOnZe9VYVdnpM0rDa8lMCagyBtzMfXJCfCmDucSRxMcpONc8icjRJ7OJnT2i3mDxwPf6M1O0utbvv1GYsuzCGTvdZGXBy3s7t6bZQ37OSsBRd5ZLee4dyOAU8mfY+No0hlOJXmkIfYUF6Gzf7zk2LEDeUtv+vYfmT1sTSB7r4u89MM+xOZL+SlnLIFnJvAwkccbEDYovzhNDur+5y8P7mdeno+Ze5xH1mdiBAR59e2BIm+ujeBd+dfeEduKvErk3NdviTxmh79Q5J3bzo5+XwIPE3mjaSnyRlRMeySBOJqMIfdxLAgL1q1hDoElIYc9+gPinBHZy14E+l7r/SDofYveqXgvgdcEpoi8/mZk9LTN03nemBD7/5P32lDePYZAHE3tHVGXtZq30DXf6+0IcFaENXE9O+qZocDbjvkRWsq+i+25JyDqkqbAO4KlHMPRCUwReUeH4PgkIAEJSEACEpDA1Qgo8q5mUecjAQlIQAISkIAEXiZ+8ULaEpCABCQgAQlIQALzCPgmbx5re5KABCQgAQlIQALTCCjypqG2IwlIQAISkIAEJDCPgCJvHmt7koAEJCABCUhAAtMIKPKmobYjCUhAAhKQgAQkMI+AIm8ea3uSgAQkIAEJSEAC0wgo8qahtiMJSEACEpCABCQwj4Aibx5re5KABCQgAQlIQALTCCjypqG2IwlIQAISkIAEJDCPgCJvHmt7koAEJCABCUhAAtMITBF5fMQ9H5Um/u9///vqng++J+QD1H5wPESMH0Wgrtv+MXTyXKPzLJMP1v/48WPYKWfI169fh3kmno8Ado7PYK8lZB0kj7jmp5yxBCTwL4EpIo+usmkreDZoFXjJ6w416cYSmElgyXmQztpV5M2xRnXsSyIPeyjy5thjRi/xAbE9MaH7C/bi0pqYMU77kMDRCTxU5LFBRwdz38hHh+j4rkeAdbkm5Fijiry5dsceI4eOrZbOkrkjtLctCETQpa0IPu573sh/pJ6xBCTw8vJQkdef0jAIh7VBAo8mEGcSsdfHo8jrRPa/H4k8RB+2UOTtz/8RPWDX7MXeP+mKvE7Fewm8JvBQkcdQeEqrwq5evx6qdxJ4DIG8Kaq9K/IqjTnXI5EXJ6/Im2ODmb3wphyb8xsF9uDoze6orGkSeFYC492zAw0242izVmeZp/IdurdJCdxNYPTGoK7buxu24rsIdJFX3/Io8t6F8jSF2XvYffTwX/+Me5oJOVAJTCbwcJHHfHliw2nmqXwyA7uTwCoBHE13Moq8VWS7ZHaRV9/0kMfP/05yF/QPbZS91/cfA9JfPNQsdn4SAocQeWxgnsrctCdZNU82TNYmQq8GRV6lMee6i7zaK2eI50clcp1rhPto/7EHDRKQwDqBKSKPAzhP2qODOq/k/e8r1o1l7jwCa+sV55J83xzNsUl4j84PRqDIm2OHGb3U/YW9u8BjDP6pdoYl7OMKBKaIvCuAcg4SkIAEJCABCUjgTAQUeWeylmOVgAQkIAEJSEACNxJQ5N0IymISkIAEJCABCUjgTAQUeWeylmOVgAQkIAEJSEACNxJQ5N0IymISkIAEJCABCUjgTAQUeWeylmOVgAQkIAEJSEACNxJQ5N0IymISkIAEJCABCUjgTAQUeWeylmOVgAQkIAEJSEACNxJQ5N0IymISkIAEJCABCUjgTAQUeWeylmOVgAQkIAEJSEACNxJ4t8gbfRScT88YJCABCUhAAhL497Nr+MW1z6/Vz7f1cmt5V+bLp03hxm/tM6dr5fiGNfVHn5wM1ysz7HO7S50BkW9FJgBzBDT5xhKQgAQkIIFnIFD9I36y+srMn+/xUi4BUZJy+ZZ7vtmLb0WcXD1k3pknTEZhrRwMwxVmuaadCLyldkd9XSFtTPGNmdVFXOG9Uc1sCUhAAhKQwKUJICIi0LogWZp4FSe9Dm/5nkHkVQZw6joj7NbKIYjrG8BqC+rnDWDaeoZ4E5EHyKqYAYchSOdXFyjlanqg53U1RiI/hiI9dYhpi7SUo6+q0OmXkI2SmDa5Tkj9np6xkW+QgAQkIAEJ3Eog/qyW7z6m5uUavxXfRVr8Hj4rvjFlrxozz8qA664rwmZULr6++/loCeqO7HNVnpnX3SIvYmi0gCPE6KSCr0ajTIRULU8d2sQYEXdZ5DFQ7ZO0tFPrZnzJow36IdRr+shCoiztEWr6rwT/kYAEJCABCawQ6P6IotVfLVWNj6v5+KP4r5p+1evql5lj1Qt1zkvlojVq2erTSY+GqGWufn23yIuSjiCroCLOIrRSBuNERNXySyKPMt2gvSzjqP1wTZlucNqpY679c53ytS3qGCQgAQlIQAK3ELhH5OGvul/EV+GT4ktv6fvsZbqvh0FewNS5LZWLD69lFXkvLx8WeSNljGEiqCrwbpzkdeEWUUh+r9PLLi2EbnDayZhon/waevma57UEJCABCUjgFgLVv+BX1t7G4T+7kOlCkfxe5pZxnK1M9+XMGX/fw1q5LuqwRQ0jvVLzr3j9msCNMwR+BBNVuK4LGcPUhc49cHu5tEF+6scIMc5bIi/liQnEtNdFWxV5XNdNk3Ewhpper29EYzEJSEACEnhiAtU/1uuOBB+FL0rAD5EWn8Y1Ya2N1L1CXH12ve5zq3n1mnIwjN+u12kjbHP/DPG7RR5CCAHGry7QpCcNwKNy5Cc9xgB00pKPMchPOvcxEGm1bkQl6RGLqRfhlnvK1v5IT1pPpz+DBCQgAQlI4D0Euj+kbvwXcfVZ8U3xnZRd8p/vGcMZy1Yu1f/CpvJZKsecoyGiBcIh/MM76VeP3y3yrg7E+UlAAhKQgAQkIIErEFDkXcGKzkECEpCABCQgAQk0Aoq8BsRbCUhAAhKQgAQkcAUCirwrWNE5SEACEpCABCQggUZAkdeAeCsBCUhAAhKQgASuQECRdwUrOgcJSEACEpCABCTQCCjyGhBvJSABCUhAAhKQwBUIKPKuYEXnIAEJSEACEpCABBoBRV4D4q0EJCABCUhAAhK4AgFF3hWs6BwkIAEJSEACEpBAI6DIa0C8lYAEJCABCUhAAlcgMEXk1e/w8d24fJOupnNtkMCRCNT1Wb+bmG8fJq7fUT7S+K8ylvqdymqHzA879e9UJs/4nATqd0aXfEO+UbqUf86ZO2oJbEtgisjLkDmIObBrGB3aNd9rCTyKwMh59PXLfU971Hiv2O/Pnz9fqohGWFe7cE2aIu9a1o9fwP7YlzghaXVdJM9YAhJ4TWCqyMvTWTYszjFv9V4PyzsJPJYADmQkHrJ2MzodTUjMiRF1nTnniCJvDv8ZvfQ9FsGXvkcvC5JnLAEJvCYwVeTRNQd0Nm0/rMnPkzkONm9I6pPbqM7rKXkngY8TiKNhvbEWl0LW8lK+6dsS4HzgV4Mir9K41jW2zl5kZrE1+4596f67lr2dzfYElr3X9n39ajGCbfTkzQbOpk05YhwtMflrDnenIdvskxNg/XVhARLeQrMmDfMI5HyoPcbx1zSvz08AH8F5X8989iK//AWIvNHePP/snYEEtiEwXeQxbDYlG7UH0rKpE8eRcq9D7cS8n0EgDxq9L9YreYY5BNj/ce61R0VepXGta/ZXFXKI/OoHlnzJtSg4GwncT+BwIm/tqSwiUMd6v8Gt+X4CrLfRuhw9qLy/dWvcQgBxt8RbkXcLwfOWYe9l/7EGcs2MuF5aF+edsSOXwHYEDiXyOKx5aouI4z6He57g2dD1SW47FLYkgTEB3h5kTaYE67E6m6Qbb08A9vXPtHCv9lDkbc/8SC3yZ9vYm32Hj0ggL74hacYSkMAfAn92y5+0Xa84rNmk/Eb/XR4HePJzsCPsUm9UZ9cB2/hTEsgaJB45EdZkHM9TApo06Tz4VXvkXGAINd+zYZJRdu6m2hS7931WfQRlDRKQwDKB6SJveSjmSEACEpCABCQgAQlsRUCRtxVJ25GABCQgAQlIQAIHIqDIO5AxHIoEJCABCUhAAhLYioAibyuStiMBCUhAAhKQgAQORECRdyBjOBQJSEACEpCABCSwFQFF3lYkbUcCEpCABCQgAQkciIAi70DGcCgSkIAEJCABCUhgKwKKvK1I2o4EJCABCUhAAhI4EAFF3oGM4VAkIAEJSEACEpDAVgQUeVuRtB0JSEACEpCABCRwIAKKvAMZw6FIQAISkIAEJCCBrQgo8rYiaTsSkIAEJCABCUjgQASmiDw+HJ4PjNe585H3pPPRaYMEjkiANVoDH0zPuvUD6ZXMPtf1g/VfvnwZdpKzhNhwDQI/fvz4tc/Yb6OAz9BvjMiYJoE/BF57rz/pm19lw/ZDmgOcPIMEjkgg4qGODYEXx8MDTK5rGa+3IQDbKtxg3x07af1c2aZ3W3kUgfiLutfqWFgXo7VQy3gtAQm8vEwVeXkir4e0Is9leFQCOBrWKs4kgfVaBQX5VYSknPE+BDpvbFHPk316tdVHEIiQGz1Esef4aftHWMY+z0Tgj/faedQ4zAg6nGbe3iUt3bNpyedXnWnyjSUwiwBOJI4mfca55L6LvqQb70OA8yGOPW97sAnnBW9VDdchkL3XRV58hiLvOrZ2JvsRmC7ymEqEHNfZsFxzaLNxExB59T7pxhLYmwBrFOcSR5P+umNR5IXMnLg++GEj7IENCIg8z4s5dpjRS/ZeF3mxcd+LM8ZkHxI4G4GHiDwgcVjzqyKvHtiUYXP7dH62JXX+8bLu8rYojiaz6o5FkRcy+8f1rKA3bbE/80f2kL1HnIDNE7r9k24sAQn8IfAwkccQ8ieW/Om2b1o2tyLvj7G8mkMgb5rznw0kZp12UUfZCMI5o3vOXvpbfijAvTr9bpvnJHWdWY9EXvZijevb3evM3plIYBsCDxV5HNxs1og8DmnuE7jXgYaG8SMIxNHUvlmjebtQr2sZr7cjAOvqyDkTSIttYov8ZWC7nm3pkQS6fftY+kuBnu+9BCQw6X9dy6GMM+RXn7wxAHkReblfKqvBJDCbQBxN7TcPJ6xTHkQM+xHIg1/OBOIq+Gq+D4T72WF2y9l3sXuEfB2HIq/S8FoCYwJ/XpuN802VgAQkIAEJSEACEjghAUXeCY3mkCUgAQlIQAISkMBbBBR5bxEyXwISkIAEJCABCZyQgCLvhEZzyBKQgAQkIAEJSOAtAoq8twiZLwEJSEACEpCABE5I4C+Rl/81k/G//2tgOcjBNeAacA24BlwDroGzrIGqRf8SeTXTawlIQAISkIAEJCCBcxJQ5J3Tbo5aAhKQgAQkIAEJrBJQ5K3iMVMCEpCABCQgAQmck4Ai75x2c9QSkIAEJCABCUhglYAibxWPmRKQgAQkIAEJSOCcBBR557Sbo5aABCQgAQlIQAKrBP4f3p98yyKptlIAAAAASUVORK5CYII=\" alt=\"\" /\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable II.\u003c/strong\u003e Univariate and multivariate analysis of 5-year OS.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tabb\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eParameter\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eUnivariate\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003eMultivariate\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eHR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eHR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e95% CI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003cp\u003e(\u0026le;\u0026thinsp;45/\u0026gt;45)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.79\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 0.71\u0026ndash;4.50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"4\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSex\u003c/p\u003e\n\u003cp\u003e(male/femal)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.92\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.37\u0026ndash;2.31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.87\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"4\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTumor size\u003c/p\u003e\n\u003cp\u003e(\u0026le;\u0026thinsp;3\u0026nbsp;cm/\u0026gt;3\u0026nbsp;cm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.77\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.07\u0026ndash;2.92\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"4\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNecrosis\u003c/p\u003e\n\u003cp\u003e(yes/no)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.68\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.67\u0026ndash;4.19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"4\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRecurrence\u003c/p\u003e\n\u003cp\u003e(yes/no)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.85\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.53\u0026ndash;13.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e3.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1.31\u0026ndash;6.86\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWHO grade\u003c/p\u003e\n\u003cp\u003e(I-II/IV)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.8-116.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e55.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.9-207.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTCF7L2 expression\u003c/p\u003e\n\u003cp\u003e(high/low)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.83\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.12\u0026ndash;2.98\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e4.91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e2.49\u0026ndash;9.69\u0026nbsp; \u0026nbsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eTCF7L2 has been reported to have an effect on the surpression of cell proliferation, migration and invasion in the literature\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e .The transcription factor 7-like 2 (TCF7L2) gene may affect cancer development and prognosis because the TCF7L2 gene play an important role in the Wnt/\u003cstrong\u003e\u0026beta;\u003c/strong\u003e-catenin signaling pathway\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e .\u003c/p\u003e\n\u003cp\u003eTo date, various biological markers have been reported in glioma\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. TCF7L2, represents a central factor in metabolism, cell proliferation, and cell apoptosis\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Bo Yu\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003eet al.found that TCF7L2 overexpression increased cell viability,migration and invasion in the cells with CRNDE inhibition.The TCF7L2 expression and prognostic value in glioma has not yet been reported.\u003c/p\u003e\n\u003cp\u003eIn our study, we detected significantly higher TCF7L2 expression in GBM tissues than in low-grade group. Moreover,TCF7L2 overexpression was significantly related with larger tumor size, higher WHO grade and necrosis.\u003c/p\u003e\n\u003cp\u003eOur study reported shorter OS in patients with higher expression, however, there was no significant difference in 2-year OS in the two groups. We found that the 2-year OS was relatively high in the patients who underwent standard therapies including radiotherapy with concomitant temozolomide (TMZ), and adjuvant TMZ after surgery,in the high expression group. There was statistically significance in 5-year survival rate (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003cp\u003eMultivariate analysis revealed that WHO grade, tumor recurrence and TCF7L2 expression level were independent prognositic factors for OS. The hazard ratio in high TCF7L2 expression group was 4.91 times more than low expression group(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05,95%CI,2.49\u0026ndash;9.69).TCF7L2 expression was independently related with the OS, indicating that higher TCF7L2 level was a marker of poor prognosis for patients.\u003c/p\u003e"},{"header":"Conclusions","content":" \u003cp\u003eTCF7L2 could be a potential prognostic factor and therapeutic target for patients with glioma.The underlying molecular mechanisms of TCF7L2 involvement in the Wnt/β-catenin signaling pathway needs to be investigated in future studies.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003eTCF7L2 Transcription factor 7-like 2\u003c/p\u003e\n\u003cp\u003eqRT-PCR Real-time quantitative PCR\u003c/p\u003e\n\u003cp\u003eOS Overall survival\u003c/p\u003e\n\u003cp\u003eTMZ Temozolomide\u003c/p\u003e\n\u003cp\u003eEMT Epithelial-mesenchymal transition\u003c/p\u003e\n\u003cp\u003eTTF Tumor Treating Fields\u003c/p\u003e\n\u003cp\u003eGBM Gliomablastoma\u003c/p\u003e\n\u003cp\u003ecDNA Complementary DNA\u003c/p\u003e\n\u003cp\u003eHR Hazard ratios\u003c/p\u003e\n\u003cp\u003eCI Confidence interval\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of Capital Medical University Sanbo Brain Hospital. Written informed consent was obtained from individual or guardian participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eL. CHEN, S. HAN and N. LIU analyzed and interpreted the glioma patient data. S.-Y. JING performed the qRT-PCR of the glioma tissues, C.-X. YAN and S.-Y. JING were major contributors in writing the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe appreciated W.-Y DENG for providing constructive suggestions to the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDarlix A, Zouaoui S, Rigau V, Bessaoud F, Figarella Branger D, MathieuDaud\u0026eacute; H, Tr\u0026eacute;tarre B, Bauchet F, Duffau H,Taillandier L,Bauchet L.Epidemiology for primary brain tumors: a nationwide population-based study. J Neurooncol.2017; 131: 525-546.\u003c/li\u003e\n\u003cli\u003eOstrom QT,Gittleman H,Fulop J,Liu M,Blanda R,Kromer C,Wolinsky Y,Kruchko C, Barnholtz-Sloan JS.CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008-2012.Neuro Oncol.2015; 17: iv1-iv62.\u003c/li\u003e\n\u003cli\u003eKoshy M,Villano JL,Dolecek TA,Howard A,Mahmood U,Chmura SJ, Weichselbaum RR,McCarthy BJ.Improved survival time trends for glioblastoma using the SEER 17 population-based registries. J Neuro-Oncol.2012; 107(1): 207-212.\u003c/li\u003e\n\u003cli\u003eStupp R,Hegi ME, Mason WP,Van den Bent MJ, Taphoorn MJB, Janzer RC, Ludwin SK,Allgeier A,Fisher B,Belanger K,Hau P,Brandes AA,Gijtenbeek J, Marosi C,Vecht CJ,Mokhtari K,Wesseling P,Villa S,Eisenhauer E,Gorlia T,Weller M, Lacombe D,Cairncross JG,Mirimanoff RO. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.Lancet Oncol.2009; 10: 459-466.\u003c/li\u003e\n\u003cli\u003eStupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, Belanger K,Brandes AA,Marosi C,Bogdahn U,Curschmann J,Janzer RC,Ludwin SK,Gorlia T,Allgeier A,Lacombe D,Cairncross JG,Eisenhauer E,Mirimanoff RO. Radiotherapy plus concomitant and adjuvant Temozolomide for glioblastoma. N Engl J Med.2005; 352: 987-996.\u003c/li\u003e\n\u003cli\u003eHrckulak D, Kolar M, Strnad H, Korinek V.TCF/LEF Transcription Factors: An Update from the Internet Resources.Cancers (Basel) 2016; 8(7): 70.\u003c/li\u003e\n\u003cli\u003eYu B,Ye X,Du Q,Zhu B, Zhai Q, Li XX.The Long Non-Coding RNA CRNDE Promotes Colorectal Carcinoma Progression by Competitively Binding miR-217 with TCF7L2 and Enhancing the Wnt/\u0026beta;-Catenin Signaling Pathway.Cell Physiol Biochem 2017; 41: 2489-2502.\u003c/li\u003e\n\u003cli\u003eStefani Spranger, Riyue Bao, Thomas F Gajewski.Melanoma-intrinsic \u0026beta;-catenin signalling prevents anti-tumour immunity.Nature 2015; 523: 231-235.\u003c/li\u003e\n\u003cli\u003eZhao C, Deng Y, Liu L, Yu K, Zhang L, Wang H, He X, Wang J, Lu C, Wu LN, Weng Q, Mao M, Li J, van Es JH, Xin M, Parry L, Goldman SA, Clevers H, Lu QR.Dual regulatory switch through interactions of TCF712/TCF4 with stage-specific partners propels oligodendroglial maturation. Nat Commun 2016; 7: 10883.\u003c/li\u003e\n\u003cli\u003eQU DW, XU HS, HAN XJ, WANG YL, OUYANG CJ. Expression of cyclinD1 and Ki-67 proteins in gliomas and its clinical significance.Eur Rev Med Pharmacol Sci 2014; 18: 516-519.\u003c/li\u003e\n\u003cli\u003eLI W, XIE P, RUAN WH. Overexpression of LncRNA UCA1 promotes osteo- sarcoma progression and correlates with poor prognosis. J Bone Oncol 2016; 5: 80- 85.\u003c/li\u003e\n\u003cli\u003eChen C, Cao FQ, Bai LP,Liu Y, Xie JL,Wang W,Si Q,Yang J, Chang AT, Liu D, Liu DC,Chuang TH, Xiang R,Luo YP.IKK\u0026beta; Enforces a LIN28B/TCF7L2 Positive Feedback Loop That Promotes Cancer Cell Stemness and Metastasis. Cancer Res 2015; 75(8): 1725-1735.\u003c/li\u003e\n\u003cli\u003eWeng QJ, Tan BQ,Wang JJ,Wang J,Zhou H,Shi J,He QJ,Yang B.5-Fluorouracil causes severe CNS demyelination by disruption of TCF7L2/HDAC1/HDAC2 complex in adolescent mice.Toxicology 2014; 325: 144-150.\u0026nbsp;\u003c/li\u003e\n\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":"Glioma, TCF7L2, Overall Survival, Prognosis, clinicopathological characteristics","lastPublishedDoi":"10.21203/rs.3.rs-130738/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-130738/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e TCF7L2 gene is known as transcription factor 7-like 2 which has been identified as a novel transcription factor epithelial-mesenchymal transition (EMT) in tumor cells at 10q25.3. TCF7L2 may affect cancer progression and plays a central role in cancer proliferation, migration and invasion. However, its clinical and prognostic value have not been researched in glioma. The purpose of our study was to research TCF7L2 expression and evaluate the clinical value of prognosis.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethod: \u003c/strong\u003eWe collected glioma specimens including low-grade glioma (n=46)and glioblastoma (n=51) from September 2015 to September 2017.Expression of TCF7L2 in 97 specimens were detected by quantitative real-time PCR (qRT-PCR).The chi-square test was applied to analyze the relationship between TCF7L2 expression and clinicopathological characteristics. The overall survival (OS) was analyzed by binary logistic regression analysis, the survival curves were drew by Kaplan-Meier. Univariate and multivariate analysis were utilized to analyze the relationship between prognosis and clinicopathological characteristics including TCF7L2 expression.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eRESULTS: \u003c/strong\u003eCompared with low-grade glioma group, the expression of TCF7L2 was significantly increased (p\u0026lt;0.05). TCF7L2 overexpression was associated with large tumor volume (p=0.03), higher WHO grade (p=0.001), and recurrence (p=0.001). Moreover, Kaplan-Meier analysis proved that overexpressed TCF7L2 was related with poor OS (p\u0026lt; 0.05).The multivariate analysis suggested that TCF7L2 expression was an independent prognostic factor.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCONCLUSIONS: \u003c/strong\u003eOur research proved that TCF7L2 was over- expressed in glioblastoma, and, related with tumor prognosis, which, therefore, could be an independent prognostic factor for glioma patients.\u003c/p\u003e","manuscriptTitle":"Expression of TCF7L2 in Glioma and Relation With Clinicopathological Characteristics and Patient Overall Survival","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-12-21 22:43:49","doi":"10.21203/rs.3.rs-130738/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":"77d74e58-3b46-4941-9412-8a3040c76620","owner":[],"postedDate":"December 21st, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":1559466,"name":"Neurology"},{"id":1559467,"name":"Neurosurgery"}],"tags":[],"updatedAt":"2020-12-21T22:43:49+00:00","versionOfRecord":[],"versionCreatedAt":"2020-12-21 22:43:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-130738","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-130738","identity":"rs-130738","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}