Identification of gene-specific DNA methylation signature for Colorectal Cancer

Colorectal Cancer (CC), a common disease causing approximately million deaths annually, has been the third most frequent type of malignancy. We aimed to identify gene-specific DNA methylation signature to function as prognostic and predictive markers for CC patient survival.

Expression profiles of gene-specific DNA methylation and the corresponding clinical information of 201 CC patients were downloaded from The Cancer Genome Atlas (TCGA) dataset and differentially expressed gene-specific DNA methylation was identified after tumor subtype classification. A risk score model was further built by analyzing the expression data of these gene-specific DNA methylations from the training dataset of CC patients.

Totally, 214 gene-specific DNA methylations were found to be expressed significantly between different subtypes of CC, including 150 up-regulated and 64 down-regulated ones. Up-regulated gene-specific DNA methylation accounted for 70.1% and the down-regulated gene-specific DNA methylation accounted for 29.9%. Hereinto, six gene-specific DNA methylations were obtained, including methy_vimentin and methy_ TFPI2, which were found significantly correlated with overall survival status of patients with CC.

With the six gene-specific DNA methylation signatures, patients in the training set were divided into low-risk and high- risk groups. What's more, gene-specific DNA methylation target genes were highly associated with protein phosphorylation, which indicated that further research on phosphorylation of target gene-coding protein might provide new sight on the treatment of CC.