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

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.

Hypermethylation of GNA14 and its tumor-suppressive role in hepatitis B virus-related hepatocellular carcinoma

“…Upregulated DNA methylation of tumor suppressive genes leads to their decreased expression, which is a crucial inducement factor for HCC 20 . HBV infection has been reported to induce gene methylation in HCC 21 . Young et al and Han et al demonstrated that HBx enhanced total DNA methyltransferase (DNMT) activity by upregulating DNMT1 and DNMT3A and selectively promoted regional hypermethylation of specific tumor suppressors 22 , 23 .…”

Peripheral Blood Genetic Biomarkers for the Early Diagnosis of Hepatocellular Carcinoma

“…ctDNA-bearing cancer-specific methylation patterns have been investigated as feasible biomarkers in cancers ( 161 ). A meta-analysis showed that the DNA methylation status of certain genes was related to the occurrence and development of HCC, including p15 and p16, APC, SPINT2, SFRP1, TFP12, GSTP1 , and RASSF1A ( 179 ). Multiple studies have shown that the methylation status of several tumor suppressor genes in HCC plasma and tumor tissue is highly consistent ( 159 ).…”

Silencing hepatitis B virus covalently closed circular DNA: The potential of an epigenetic therapy approach

“…These results show the impact methylation can have on viral gene expression in CHB[ 78 ]. A recent comprehensive meta-analysis revealed significant hypermethylation of certain host genes depending on the geographical location of the population[ 79 ]. This included six genes in HBV-positive carcinoma tissues ( p16 , RASSF1A , GSTP1 , APC , p15 and SFRP1), two genes in HBV-positive carcinoma sera ( p16 and APC ) and one gene in HBV-positive adjacent tissues ( GSTP1 ).…”