Genomic Effect of DNA Methylation on Gene Expression in Colorectal Cancer

The aberrant expression of cancer-related genes can lead to colorectal cancer (CRC) carcinogenesis, and DNA methylation is one of the causes of abnormal expression. Although many studies have been conducted to reveal how DNA methylation affects transcription regulation, the ways in which it modulates gene expression and the regions that significantly affect DNA methylation-mediated gene regulation remain unclear. In this study, we investigated how DNA methylation in specific genomic areas can influence gene expression. Several regression models were constructed for gene expression prediction based on DNA methylation. Among these models, ElasticNet, which had the best performance, was chosen for further analysis. DNA methylation near transcription start sites (TSS), especially from 2 kb upstream to 7 kb downstream of TSS, had an essential regulatory role in gene expression. Moreover, methylation-affected and survival-associated genes were compiled and found to be mainly enriched in immune-related pathways. This study investigated genomic regions in which methylation changes can affect gene expression. In addition, this study proposed that aberrantly expressed genes due to DNA methylation can lead to CRC pathogenesis by the immune system.