Gene screening for primary non-response to infliximab in intestinal mucosa of patients with ulcerative colitis

  Objective  To screen differentially expressed genes (DEGs) of responding patients and those with primary non-response to infliximab of ulcerative colitis (UC) treated with infliximab (IFX), and to perform biological analysis, and to predict potential targets for UC patients being unresponsive to IFX.

  Methods  The GEO2R online tool software was used to analyze the data sets such as GSE14580, GES12251 and GSE23597 in IFX-treated UC patient to obtain DEGs; the DEGs-protein interaction (PPI) network was constructed through the String database, and the function and signal pathway enrichment analysis was performed with David software; key genes were screened through Cytoscape and cytoHubba plug-ins and imported into the DGIdb database to find potentially effective biological agents.

  Results  A total of 143 UC patients with UC patients with primary failure to respond to IFX treatment were screened for DEGs, including 10 up-regulated genes and 133 down-regulated genes; GO and KEGG analysis indicated that DEGs were mainly enriched in inflammation, immune response, response to vitamin D, TLR pathway, and TNF signaling pathways. Using Cytoscape and cytoHubba software, the top 20 key genes with the highest scores were screened and imported into the DGIdb database. The top three potentially effective biologics were sarilumab, avacopan, and toralimab.

  Conclusion  There are a total of 143 DEGs in the samples of UC with primary non-response to infliximab, DEGs are mainly enriched in the regulation of interleukin-6 production, the response to vitamin D, the TLR pathway and the TNF signaling pathway, etc. Salilumab, avacopan and tomaralimab are potential therapeutic drugs for UC patients who fail to respond to IFX treatment.