Comparative study of under-expressed prognostic biomarkers and pivotal signaling pathways in colon cancer and ulcerative colitis using integrated bioinformatics approach

Abstract: Colon cancer is a prevalent gastrointestinal malignancy arising in the colon. Ulcerative colitis(UC) is one of the risk factors of colorectal cancer. The detection of under-expressed biomarkers and molecular mechanisms in UC and colon cancer can lead to effective management of colitis-associated cancer. A total of two mRNA expression datasets (GSE87473 and GSE44076) were downloaded from the Gene Expression Omnibus (GEO) database. GEO2R was used to screen differentially expressed genes (DEGs) between extensive ulcerative colitis samples and healthy samples, limited ulcerative colitis samples and healthy samples, and colon cancer samples and healthy samples. In extensive ulcerative colitis, limited ulcerative colitis and colon cancer groups, 95,69 and 635 under-expressed genes with adjusted p-value<0.05 and log(2) fold change<-2 were detected respectively. Using Cytoscape software, the genes with degree> 15 including CLCA1, SLC26A3, SI, KIT, HPGDS, NR1H4, ADIPOQ, PPARGC1A, GCG, MS4A12, GUCA2A and FABP1 were screened as hub under-expressed genes in colon cancer. In extensive ulcerative colitis, the genes with degree>5 including ABCB1, ABCG2, UGT1A6, CYP2B6 and AQP8 were identified as hub genes. Moreover, the genes including NR1H4, CYP2B6, ABCB1, ABCG2, UGT2A3 and PLA2G12B were detected as hub genes with degree>5 in limited ulcerative colitis. According to inclusion criteria and venn diagram, the downregulated gene NR1H4 was common gene in limited ulcerative colitis and colon cancer. The current in silico study showed that downregulation of CLCA1, PPARGC1A and AQP8 genes may increase cancer cell invasion and metastasis ability.