4.6 Article

Epigenome-Wide DNA Methylation Profiling in Colorectal Cancer and Normal Adjacent Colon Using Infinium Human Methylation 450K

Journal

DIAGNOSTICS
Volume 12, Issue 1, Pages -

Publisher

MDPI
DOI: 10.3390/diagnostics12010198

Keywords

colorectal cancer; DNA methylation; adjacent normal colon; Infinium Human Methylation 450K; microarray

Funding

  1. University Research Grant Scheme from the Universiti Kebangsaan Malaysia [GUP-2018-070]
  2. Higher Institution Centre of Excellence (HiCOE) grant from the Ministry of Higher Education [HICOE 10-64-01-005]

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This study profiles the DNA methylation in colorectal cancer (CRC) and identifies several potential important methylated genes, which may serve as novel candidate biomarker genes in CRC. Aberrant DNA methylation is significantly involved in CRC pathogenesis and is associated with gene silencing.
The aims were to profile the DNA methylation in colorectal cancer (CRC) and to explore cancer-specific methylation biomarkers. Fifty-four pairs of CRCs and the adjacent normal tissues were subjected to Infinium Human Methylation 450K assay and analysed using ChAMP R package. A total of 26,093 differentially methylated probes were identified, which represent 6156 genes; 650 probes were hypermethylated, and 25,443 were hypomethylated. Hypermethylated sites were common in CpG islands, while hypomethylated sites were in open sea. Most of the hypermethylated genes were associated with pathways in cancer, while the hypomethylated genes were involved in the PI3K-AKT signalling pathway. Among the identified differentially methylated probes, we found evidence of four potential probes in CRCs versus adjacent normal; HOXA2 cg06786372, OPLAH cg17301223, cg15638338, and TRIM31 cg02583465 that could serve as a new biomarker in CRC since these probes were aberrantly methylated in CRC as well as involved in the progression of CRC. Furthermore, we revealed the potential of promoter methylation ADHFE1 cg18065361 in differentiating the CRC from normal colonic tissue from the integrated analysis. In conclusion, aberrant DNA methylation is significantly involved in CRC pathogenesis and is associated with gene silencing. This study reports several potential important methylated genes in CRC and, therefore, merit further validation as novel candidate biomarker genes in CRC.

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