Elsevier

Neoplasia

Volume 22, Issue 3, March 2020, Pages 154-161
Neoplasia

Original Research
Epigenomic analysis of 5-hydroxymethylcytosine (5hmC) reveals novel DNA methylation markers for lung cancers

https://doi.org/10.1016/j.neo.2020.01.001Get rights and content
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Abstract

Background

DNA methylation at the fifth position of cytosine (5mC) is a common epigenetic alteration affecting a range of cellular processes. In recent years, 5-hydroxymethylcytosine (5hmC), an oxidized form of 5mC, has risen broad interests as a potential biomarker for lung cancer diagnosis and survival.

Methods

We analyzed the epigenome-wide 5hmC profiles of paired lung tumor and adjacent normal tissues, using the TET-Assisted Bisulfite (TAB) array – Infinium MethylationEPIC BeadChip (EPIC) approach. The differentially methylated CpG sites were identified, and the biological relevance of 5hmC was assessed by differential methylation regions (DMR) analysis and gene set analysis (GSA).

Results

We observed global hypomethylation of 5hmC comparing tumor to normal tissues, and hypermethylated 5hmC were enriched in CpG islands and gene upstream. Comparison of 5hmC and 5modC (total methylation: 5mC + 5hmC) profiling showed low correlation, and only a small proportion of the significant 5hmC loci overlapped with the significant total methylation loci. GSA analysis suggested that 5hmC was mainly involved in biological processes such as cellular process, biological regulation, and metabolic process.

Conclusion

This is the first study to analyze the epigenome-wide 5hmC profiles among paired lung tumor and normal tissues. We observed global hypomethylation of 5hmC in lung cancers, and hypermethylated 5hmC enriched in CpG islands and gene upstream. We found that the genome-wide 5hmC levels do not correlate with the total methylation, and the GSA suggested different biological functions of 5hmC compared to 5modC. Overall, our results demonstrate the potential of 5hmC as a novel biomarker for lung cancer.

Keywords

Lung neoplasms
Epigenomics
Biomarkers
Methylation
5-Hydroxymethylcytosine

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