Deregulation of expression by promoter methylation in gastrointestinal cancers.

, a basic helix-loop-helix transcription factor with versatile roles in cancer, is frequently deregulated in cancers, through established pathway perturbations. However. the significance of methylation in the deregulation of in gastrointestinal cancers is not fully clear. This study hypothesized that promoter methylation deregulates expression independent of established deregulators such as the , , and miRNA pathways. To prove this hypothesis, colon, gastric and rectal cancer genomic data comprising gene expression, DNA methylation, and miRNA data were retrieved from the Cancer Genome Atlas cohorts which are publicly available in cancer genomic databases, the Genome Data Commons and the cBioportal.org. About 217 variables comprising expression levels of genes of the , , and miRNA signalling pathways, as well as the beta values of 17 methylation loci were subjected to Principal Component Regression Analysis, and then standard Linear Regression Analysis. The results showed that methylation is a predictor of expression in the gastrointestinal cancers, independent of , , and signalling and miRNA deregulation. The results also showed that different methylation loci may deregulate expression in different cancer types. The inference that can be drawn from this study is that DNA methylation is an important deregulation mechanism in colon, rectal and gastric cancers.