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Global analysis of DNA methylation in hepatocellular carcinoma by a liquid hybridization capture-based bisulfite sequencing approach

Lookup NU author(s): Dr Arian Laurence



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Background: Epigenetic alterations, such as aberrant DNA methylation of promoter and enhancer regions, which lead to atypical gene expression, have been associated with carcinogenesis. In hepatocellular carcinoma (HCC), genome-wide analysis of methylation has only recently been used. For a better understanding of hepatocarcinogenesis, we applied an even higher resolution analysis of the promoter methylome to identify previously unknown regions and genes differentially methylated in HCC.Results: Optimized liquid hybridization capture-based bisulfite sequencing (LHC-BS) was developed to quantitatively analyze 1.86 million CpG sites in individual samples from eight pairs of HCC and adjacent tissues. By linking the differentially methylated regions (DMRs) in promoters to the differentially expressed genes (DEGs), we identified 12 DMR-associated genes. We further utilized Illumina MiSeq combining the bisulfite sequencing PCR approach to validate the 12 candidate genes. Analysis of an additional 78 HCC pairs on the Illumina MiSeq platform confirmed that 7 genes showed either promoter hyper-methylation (SMAD6, IFITM1, LRRC4, CHST4, and TBX15) or hypo-methylation (CCL20 and NQO1) in HCC.Conclusions: Novel methylome profiling provides a cost-efficient approach to identifying candidate genes in human HCC that may contribute to hepatocarcinogenesis. Our work provides further information critical for understanding the epigenetic processes underlying tumorigenesis and development of HCC.

Publication metadata

Author(s): Gao F, Liang HF, Lu HL, Wang JW, Xia M, Yuan ZM, Yao Y, Wang T, Tan XL, Laurence A, Xu H, Yu JJ, Xiao W, Chen W, Zhou M, Zhang XQ, Chen Q, Chen XP

Publication type: Article

Publication status: Published

Journal: Clinical Epigenetics

Year: 2015

Volume: 7

Online publication date: 21/08/2015

Acceptance date: 03/08/2015

Date deposited: 16/10/2015

ISSN (electronic): 1868-7083

Publisher: BioMed Central Ltd.


DOI: 10.1186/s13148-015-0121-1


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Funder referenceFunder name
2009010016Innovative R&D Team Program of Guangdong Province
201302009Major Science Foundation of the Ministry of Health of China
2012AA02A201Chinese 863 Program
2012ZX10002010-001-004Major and Special Program of National Science and Technology in Twelfth Five-year Plan of China
2012ZX10002016-004Major and Special Program of National Science and Technology in Twelfth Five-year Plan of China
81202300National Natural Science Foundation of China
81471612National Natural Science Foundation of China
31200666National Natural Science Foundation of China
81372495National Natural Science Foundation of China