Integrated bioinformatics identifies the dysregulation induced by aberrant gene methylation in colorectal carcinoma

Abstract

Colorectal carcinoma (CRC) is one of the most common cancers, and is associated with a poor clinical outcome. The key genes and potential prognostic markers in colorectal carcinoma remain to be identified and explored for clinical application. DNA expression/methylation profiles were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed/methylated genes (DEGs and DEMs). A total of 255 genes and 372 genes were identified as being up-regulated and down-regulated, respectively, in GSE113513, GSE81558, and GSE89076. There were a total of 3350 hypermethylated genes and 443 hypomethylated genes identified in GSE48684. Twenty genes were found to be hypermethylated as well as down-regulated, and a functional enrichment analysis revealed that these genes were mainly involved in cancer-related pathways. Among these 20 genes, GPM6A, HAND2 and C2orf40 were related to poor outcomes in cancer patients based on a survival analysis. Concurrent decreases of GPM6A, HAND2 and C2orf40 protein expression were observed in highly-differentiated colorectal carcinoma tissues, and higher expression levels were found in undifferentiated or minimally-differentiated colorectal carcinoma tissues. In conclusion, 20 genes were found to be downregulated and hypermethylated in CRC, among which GPM6A, HAND2 and C2orf40 were explored for their potential prognostic value.

Keywords

• Bioinformatics
• C2orf40
• Colorectal carcinoma
• GPM6A
• HAND2
• Hypermethylation