Abstract
The methylome of open chromatins was investigated in colorectal cancer (CRC) to explore cancer-specific methylation and potential biomarkers. Epigenome-wide methylome of open chromatins was studied in colorectal cancer tissues using the Infinium DNA MethylationEPIC assay. Differentially methylated regions were identified using the ChAMP Bioconductor. Our stringent analysis led to the discovery of 2187 significant differentially methylated open chromatins in CRCs. More hypomethylated probes were observed and the trend was similar across all chromosomes. The majority of hyper- and hypomethylated probes in open chromatin were in chromosome 1. Our unsupervised hierarchical clustering analysis showed that 40 significant differentially methylated open chromatins were able to segregate CRC from normal colonic tissues. Receiver operating characteristic analyses from the top 40 probes revealed several significant, highly discriminative, specific and sensitive probes such as OPLAH cg26256223, EYA4 cg01328892, and CCNA1 cg11513637, among others. OPLAH cg26256223 hypermethylation is associated with reduced gene expression in the CRC. This study reports many open chromatin loci with novel differential methylation statuses, some of which with the potential as candidate markers for diagnostic purposes.
Highlights
Cancer is a continuous global burden with an estimation of over 18.1 million new incidences and projected to increase in the decade [1]
Further understanding of the epigenetic components in the processes involved in colorectal cancer (CRC) carcinogenesis is highly desired and will unravel new biomarkers which can be utilized for diagnosis, prognosis and treatment to prevent CRC-related mortality
We focused on the genome-wide methylation patterns of open chromatins among CRC patients
Summary
Cancer is a continuous global burden with an estimation of over 18.1 million new incidences and projected to increase in the decade [1]. Within these statistics, colorectal cancer (CRC) contributes around 1.1 million (6%) of total cases and is ranked as the fourth most common cancer in the world [1]. Despite many kinds of research on molecular alterations involved in CRC pathogenesis, the existing knowledge remains inadequate for early diagnosis and prognosis assessment. Further understanding of the epigenetic components in the processes involved in CRC carcinogenesis is highly desired and will unravel new biomarkers which can be utilized for diagnosis, prognosis and treatment to prevent CRC-related mortality. One of the candidates for the biomarkers could be discovered from analysing the epigenome of the tumours
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