Expression And Prognostic Correlation Analysis Of GLP-2R Gene In Colorectal Cancer

Purpose:Worldwide,colorectal cancer（CRC）is a cancer with high incidence and mortality rates.In clinical,it is urgent to discover its effective biomarkers for early diagnosis and accurately prognosis.Glucagon-like peptide-2 receptor（GLP-2R）,a member of G protein-coupled receptor（GPCR）subfamily,has been confirmed to perform favorable functions on inflammatory intestinal disorders,whereas their role in CRC patients remain to be revealed.Materials and methods:In this study,TCGA,GTEx,GEPIA and HPA databases were performed to examine the expression of GLP-2R in CRC and normal colorectal tissues.Receiver operating characteristic（ROC）curve was used to reveal the diagnostic value of GLP-2R gene in CRC.Chi-square test was used to analyze the correlation between GLP-2R gene expression and clinicopathological factors in CRC patients.The prognostic value of GLP-2R gene in CRC patients was evaluated by univariate and multivariate Cox regression analyses and Kaplan-Meier curve,and a GLP-2R-related Nomogram prognostic model of CRC patients was established.The accuracy of this prognostic model was evaluated using calibration curves.Besides,the correlation between GLP2R and 37 immune-related genes along with immune infiltrating lymphocytes were identified to use ggplot2 and ssGSEA methods.The functional enrichment pathways of GLP-2R related co-expressed differentially genes in CRC patients were established by using gene ontology（GO）,Kyoto Encyclopedia of Genes and Genomes（KEGG）and Gene Set Enrichment Analysis（GSEA）.Protein-protein interaction（PPI）analysis was used to further verify its potential function.Results:In the study,it was found that GLP-2R gene expression was significantly down-regulated in CRC tissues compared with that in the normal colorectal tissues,even in the earliest stage（P<0.001）,ROC curve indicated that GLP-2R expression exhibit a good diagnostic accuracy in CRC patients with high sensitivity and specificity.Univariate and multivariate COX regression analyses showed that low GLP-2R expression was an independent predictor of poor prognosis of CRC patients.Compared with that in the relatively high GLP-2R expression group,CRC patients with low GLP-2R expression had a worse overall survival（P<0.05）.GO and KEGG functional enrichment analyses showed that GLP-2R associated with normal intestinal and colonic growth as well as cellular communication and connection.In addition,GSEA analysis suggested that GLP-2R expression was associated with many immune-related pathways,among which B cell-related adaptive immune regulation is most significant.Notably,high GLP-2R expression in tumor lesions is significantly associated with high expression of more crucial immune-related genes and high levels of immunocyte infiltration.Based on independent prognostic factors involving GLP-2R expression,we constructed a prognostic Nomogram model of CRC patients.The prognostic model had high accuracy in predicting survival,and its calibration curve was close to the ideal line.Conclusion:GLP-2R expression is significantly decreased in colorectal cancer tissues and is an independent factor affecting the prognosis of CRC.The Nomogram prognostic model associated with GLP-2R expression can effectively predict the prognosis and survival of CRC patients with high accuracy.The level of GLP-2R expression is related to the tumoral immune microenvironment of CRC patients,and the CRC patients with low GLP2R expression group have a lower level of immune cell infiltration.