Genome-wide DNA methylation analysis of colorectal cancer and polyp

Colorectal polyp is known a precursor of colorectal cancer (CRC) that holds an increased risk for progression to CRC. Circulating cell-free DNA(cfDNA) methylation has shown favorable performance in the detection and monitoring the malignant progression in a variety of cancers. Here, we conducted a study to discovery cfDNA methylation markers for the diagnosis of CRC. We first performed a genome-wide analysis using the Infinium HumanMethylationEPIC BeadChip array to identify differentially methylated CpGs (DMCs) between 8 CRC and 8 polyp tissues. Then, we validated DMCs in a larger tissue cohort and four methylation markers (cg04486886, cg06712559, cg13539460 and cg27541454) were selected as the methylation markers in tissue by LASSO and random forest models. A diagnosis prediction model was bulit based on the four markers and the methylaion diagnosis score (md-score) can effectively discriminate patients with CRC from polyp tissues. Finally, a single cfDNA methylation marker, cg27541454, was confirmed hypermethylated in CRC in the plasma validation cohort. Together, our findings suggested that the md-score derived from tissue could robustly detect CRC from polpy patients, and cg27541454 may be a promising candidate non-invasive biomarker for CRC early diagnosis. Tissue samples from colorectal cancer (n=8) and polyp (n=8) patients were hybridized by the Illumina Infinium EPIC Human Methylation BeadChip, following DNA extraction and bisulphite treatment.