Journal
CLINICAL EPIGENETICS
Volume 12, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13148-020-00851-3
Keywords
DNA methylation; Low-grade adenoma; High-grade adenoma; Colorectal cancer; Biomarker
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Funding
- Youth Innovation Promotion Association CAS [2016098]
- Major State Basic Research Development Program [2014CB542006]
- Key Research Program of the Chinese Academy of Sciences [KJZD-EW-L14]
- National Key Research and Development Plan of China [2016YFA0201404]
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Background Abnormal DNA methylation is a hallmark of human cancers and may be a promising biomarker for early diagnosis of human cancers. However, the majority of DNA methylation biomarkers that have been identified are based on the hypothesis that early differential methylation regions (DMRs) are maintained throughout carcinogenesis and could be detected at all stages of cancer. Methods In this study, we identified potential early biomarkers of colorectal cancer (CRC) development by genome-wide DNA methylation assay (Illumina infinium450, 450 K) of normal (N = 20) and pre-colorectal cancer samples including 18 low-grade adenoma (LGA) and 22 high-grade adenoma (HGA), integrated with GEO and ArrayExpress datasets (N = 833). Results We identified 209 and 8692 CpG sites that were significantly hyper-methylated in LGA and HGA, respectively. Pathway analysis identified nervous system-related methylation changes that are significantly associated with early adenoma development. Integration analysis revealed that DNA methylation in the promoter region of ADHFE1 has the most potential for being an early diagnostic biomarker for colorectal adenoma and cancer (sensitivity = 0.96, specificity = 0.95, area under the curve = 0.97). Conclusions Overall, we demonstrated that DNA methylation have been shown significant changes in the stage of LGA and HGA in the development of colon cancer. Genome-wide DNA methylation to LGA and HGA provided an important proxy to identify promising early diagnosis biomarkers for colorectal cancer.
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