J Cancer 2019; 10(25):6457-6465. doi:10.7150/jca.33005

Research Paper

Association between gene methylation and HBV infection in hepatocellular carcinoma: A meta-analysis

Cheng Zhang1✉, Changxin Huang1, Xinbing Sui1, Xueqing Zhong2, Wenjun Yang3, Xiangrong Hu3, Yongqiang Li1,4✉

1. Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
2. Department of Gastroenterology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
3. Department of Pathology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
4. Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province, Hangzhou, Zhejiang, China

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Zhang C, Huang C, Sui X, Zhong X, Yang W, Hu X, Li Y. Association between gene methylation and HBV infection in hepatocellular carcinoma: A meta-analysis. J Cancer 2019; 10(25):6457-6465. doi:10.7150/jca.33005. Available from http://www.jcancer.org/v10p6457.htm

File import instruction

Abstract

Gene methylation is an epigenetic alteration in hepatocellular carcinoma (HCC), and hepatitis B virus (HBV) plays a crucial role in carcinogenesis of HCC. However, the association between gene methylation and HBV infection in HCC remains unclear. In our study, we conducted a comprehensive meta-analysis to evaluate the association. A total of 1,148 studies were initially retrieved from some literature database. After a four-step filtration, we obtained 69 case-control studies in this meta-analysis. Our results showed six genes (p16, RASSF1A, GSTP1, APC, p15 and SFRP1) in HBV-positive carcinoma tissues, one gene (GSTP1) in HBV-positive adjacent tissues and two gene (p16 and APC) in HBV-positive carcinoma serums, which were significantly hypermethylated. Subgroup meta-analysis by geographical populations revealed that GSTP1 methylation was significantly higher in HBV-positive carcinoma tissues in China and Japan. In addition, p16 and RASSF1A methylation was significantly higher in China but not in Japan. Our study indicated that HBV infection could induce DNA methylation in HCC and DNA methylation could lead to the development of HBV-related HCC.

Keywords: meta-analysis, gene methylation, hepatitis B virus, hepatocellular carcinoma