Bioinformatics analyses of key genes related with the efficacy of infliximab treatment in patients with inflammatory bowel diseases

Abstract

Objective To search the colonic mucosal key genes related with the efficacy of infliximab (IFX) treatment in patients with inflammatory bowel disease (IBD). Methods By bioinformatics method, using GEO database colonic mucosal microarray data of ulcerative colitis (UC) and Crohn’s colitis (CDc) before IFX treatment, gene set enrichment analysis (GSEA) was used to screen the co-enrichment gene ontology (GO) gene sets for CDc and UC. Then, the genes in the co-enrichment GO gene sets were extracted for establishment of the interaction network in STRING database. The center node that had the maximum interactions of the interaction network was screened in cytoscape software, meanwhile, the first neighbors of the node that had more than three interactions were also screened. Finally, STRING database was used to analyze Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the selected genes and find related signaling pathways and intergenic interaction in order to detect the mechanism of these genes related with IFX efficacy. Results Positive regulation of protein metaboloc process was the co-enrichment GO gene set in which 70 genes of unresponsive patients derived from the included datasets were upregulated [false discovery rate (FDR) <25%]. Interleukin-6 (IL-6) was screened out to be the center node of the genetic interaction network, which was constituted by 70 genes and their interactions, and 17 of its first neighbors were found. Eighteen selected genes involved in three main KEGG pathways, including Toll-like receptor signaling pathway, Janus kinase (JAK)-signal transducer and activators of transcription (STAT) signaling pathway and cytokine-cytokine receptor interaction, which played roles in inflammation. Especially, IL-6 involved in the above three pathways. Conclusion The response to IFX in patients with UC and CDc was related to the expression of IL-6 that could promote colonic inflammation in several different pathways, which can provide clues to predict the response to IFX before treatment. Key words: Inflammatory bowel diseases; Infliximab treatment; Efficacy; Genes; Bioinformatics