Genome-wide methylation profiling of the different stages of hepatitis B virus-related hepatocellular carcinoma development in plasma cell-free DNA reveals potential biomarkers for early detection and high-risk monitoring of hepatocellular carcinoma

Clinical Epigenetics

Qiang Xia¹  Jian Yu⁷  Yinghua He⁵  Ning Tang⁵  Zhenfeng Zhang⁷  Wei Wang⁷  Xiaoyu Zhou³  Jun Gu⁷  Junfeng Geng⁴  Bijun Qiu¹  Hongyu Zhang⁵  Shicheng Guo²  Jinfeng Sun⁶  Feng Xue¹  Yangxing Zhao⁷ 

[1] Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China;Ministry of Education Key Laboratory of Contemporary Anthropology School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China;Key Laboratory of Contraceptive Drugs and Devices of NPFPC, Shanghai Institute of Planned Parenthood Research, 2140 Xietu Road, Shanghai 200032, China;Department of General Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, China;Shanghai Cancer Institute,Renji Hospital, Shanghai Jiao Tong University School of Medicine, LN 2200/25,Xietu Road, Shanghai 200032, China;Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China;State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, LN 2200/25,Xietu Road, Shanghai 200032, China

关键词: DNA methylation;    Genome-wide;    HCC development;    HBV;    Cell-free DNA;    Plasma;   

Others  :  1092764
DOI  :  10.1186/1868-7083-6-30

 received in 2014-09-02, accepted in 2014-11-14,  发布年份 2014

【 摘 要 】

Background

An important model of hepatocellular carcinoma (HCC) that has been described in southeast Asia includes the transition from chronic hepatitis B infection (CHB) to liver cirrhosis (LC) and, finally, to HCC. The genome-wide methylation profiling of plasma cell-free DNA (cfDNA) has not previously been used to assess HCC development. Using MethylCap-seq, we analyzed the genome-wide cfDNA methylation profiles by separately pooling healthy control (HC), CHB, LC and HCC samples and independently validating the library data for the tissue DNA and cfDNA by MSP, qMSP and Multiplex-BSP-seq.

Results

The dynamic features of cfDNA methylation coincided with the natural course of HCC development. Data mining revealed the presence of 240, 272 and 286 differentially methylated genes (DMGs) corresponding to the early, middle and late stages of HCC progression, respectively. The validation of the DNA and cfDNA results in independent tissues identified three DMGs, including ZNF300, SLC22A20 and SHISA7, with the potential for distinguishing between CHB and LC as well as between LC and HCC. The area under the curve (AUC) ranged from 0.65 to 0.80, and the odds ratio (OR) values ranged from 5.18 to 14.2.

Conclusions

Our data revealed highly dynamic cfDNA methylation profiles in support of HBV-related HCC development. We have identified a panel of DMGs that are predictive for the early, middle and late stages of HCC development, and these are potential markers for the early detection of HCC as well as the screening of high-risk populations.

【 授权许可】

   
2014 Zhao et al.; licensee BioMed Central Ltd.

【 图 表 】

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