An integrative study on the impact of highly differentially methylated genes on expression and cancer etiology.

Abstract

DNA methylation is an important epigenetic phenomenon that plays a key role in the regulation of expression. Most of the studies on the topic of methylation's role in cancer mechanisms include analyses based on differential methylation, with the integration of expression information as supporting evidence. In the present study, we sought to identify methylation-driven patterns by also integrating protein-protein interaction information. We performed integrative analyses of DNA methylation, expression, SNP and copy number data on paired samples from six different cancer types. As a result, we found that genes that show a methylation change larger than 32.2% may influence cancer-related genes via fewer interaction steps and with much higher percentages compared with genes showing a methylation change less than 32.2%. Additionally, we investigated whether there were shared cancer mechanisms among different cancer types. Specifically, five cancer types shared a change in AGTR1 and IGF1 genes, which implies that there may be similar underlying disease mechanisms among these cancers. Additionally, when the focus was placed on distinctly altered genes within each cancer type, we identified various cancer-specific genes that are also supported in the literature and may play crucial roles as therapeutic targets. Overall, our novel graph-based approach for identifying methylation-driven patterns will improve our understanding of the effects of methylation on cancer progression and lead to improved knowledge of cancer etiology.