Bioinformatics Analysis For Non-response Of Infliximab To Ulcerative Colitis Based On GEO Database

Objective:The incidence of ulcerative colitis is on the rise in China Infliximab is the first biological agent approved for the treatment of moderate and severe ulcerative colitis with good efficacy,but one third of patients show no response to it Therefore,this project will analyze the key predictors of non-response of infliximab in patients with ulcerative colitis and its related mechanisms through bioinformatics,so as to provide personalized treatment options for patients with ulcerative colitis.Methods:1.Data sets GSE73661 and GSE14580 were downloaded from Gene Expression Omnibus(GEO)database,and Limma packet in R language was used to analyze and screen differentially expressed genes(DEGs).2.Gene Oncology(GO)analysis of DEGs was conducted on the website of David and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of DEGs was conducted in R language using clusterProfiler package;3.Build protein-protein interaction(PPI)network through String database,import the obtained source files into Cytoscape software for visual analysis of PPI network,and screen key genes with MCODE and Cytohubba plug-ins;4.Download the validation data set GSE12251 from GEO,and use the expression levels of key genes in it to do the ROC(Receiver Operation Characteristic)analysis and calculate the Area under curve(AUC).Results:1.A total of 75 DEGs were screened out in GEO dataset,including 72 up-regulated genes and 3 down-regulated genes.Its biological functions are mainly related to inflammatory response,immune response,chemokine-mediated chemotaxis of inflammatory cells,signal transduction,cell response to inflammatory factors,cell adhesion and repair ability,protein hydrolysis and other processes.Molecular functions mainly involve the activities of chemokines and cytokines,the activities of serine endopeptidase and metal endopeptidase,and the binding of heparin.2.The PPI network indicated that the non-response of infliximab was affected by the interaction of multiple proteins,and 15 core genes including IL6,CXCL8,CCL2,IL1B,CXCL10,CXCL9,MMP2,CXCL6,CXCL5,MMP3,CCL4,GPR183,PTGS2,MMP1 and P2RY13 were obtained by Cytoscape software analysis.3.ROC analysis showed that IL6,CXCL8,IL1B,CXCL6,MMP3,CCL4,PTGS2,MMP1,and P2Ry13 might be the key predictors of infliximab non-response,and IL-17 signaling pathway might be the crucial mechanism.