Identification and analysis of key genes associated with ulcerative colitis based on DNA microarray data.

Abstract

This study aimed to identify genes that may play a role in development of ulcerative colitis (UC) and gain insight into its pathogenesis.Gene expression profiling data, including samples collected from 13 early-stage UC (EUC), 8 advanced-stage UC (AUC), and 5 control subjects, were downloaded from the Gene Expression Omnibus database under the accession number of GSE9452. Differentially expressed genes (DEGs) were identified in EUC and AUC compared with controls. DEGs for EUC and AUC, as well as AUC-specific DEGs were subjected to pathway enrichment analysis. Random Walk with Restart (RWR) was used to identify DEGs that are critical in UC based on a protein-to-protein interaction (PPI) network and the inflammatory bowel disease (IBD) pathway downloaded from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. IL17 and transforming growth factor beta TGF-β) expression levels in colonic tissue from patients with UC and normal colonic mucosa from healthy adults were analyzed by immunohistochemistry (IHC).A total of 3511 and 911 DEGs were identified in AUC and EUC, respectively. The overlapping DEGs and the AUC-specific DEGs were both enriched in pathways related to immunity, such as antigen processing and presentation. AUC-specific DEGs were related to cell migration, such as ECM-receptor interaction. Following DEG prioritization, TLR4 and STAT1 were linked with EUC, AUC, and CD. The upregulated gene TGFB increased the number of Th17 cells, as verified by IHC. Furthermore, PIK3R1, CREBBP, and STAT1 were part of high-degree nodes in the PPI sub-network.The upregulated gene TGFB may regulate IL17 expression in UC. PIK3R1 may participate in immunity and CREBBP may interact with STAT1 in the development and progression of UC.