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. 2018 Sep 12:11:5789-5796.
doi: 10.2147/OTT.S168444. eCollection 2018.

Association of GSTP1 and P16 promoter methylation with the risk of HBV-related hepatocellular carcinoma: a meta-analysis

Qin Li  1 , Cunliang Deng  1 , Ting Zhang  1 , Xiang Li  2
Affiliations

Association of GSTP1 and P16 promoter methylation with the risk of HBV-related hepatocellular carcinoma: a meta-analysis

Qin Li et al. Onco Targets Ther. .

Abstract

Background: Study on the relationship between glutathione-S-transferase Pi 1 (GSTP1) and P16 promoter region methylation and the risk of hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) has produced inconsistent results.

Objectives: To assess the correlation between GSTP1 and P16 promoter methylation frequency and HBV-related HCC susceptibility.

Methods: All relevant studies were identified by searching PubMed, Embase, Web of Science, and China National Knowledge Infrastructure literature databases before December, 2017. The OR and the corresponding 95% CI were calculated to investigate the risk of GSTP1 and P16 promoter methylation rate and HBV-related HCC. Sensitivity analysis was performed and publication bias was estimated using the Begg's and Egger's test.

Results: Our meta-analysis identified the relationships of GSTP1 (six studies including 213 HBV-related HCC tumor tissues) and P16 (nine studies with 287 HBV-related HCC tumor tissue) promoter methylation with HCC risk. Compared with normal liver tissue and cirrhosis, the pooled ORs of GSTP1 promoter region methylation in HBV-related HCC cancer tissues were 6.05 (95% CI =1.20-30.52) and 5.21 (95% CI =2.19-12.41), respectively. Compared with paracancerous tissue, normal liver tissue, cirrhosis, and chronic hepatitis B as controls, the pooled ORs of P16 promoter region methylation in HBV-related HCC cancer tissues were 7.18 (95% CI =2.31-22.33), 24.89 (95% CI =3.38-183.03), 5.92 (95% CI =1.78-19.68), and 12.12 (95% CI =0.75-196.50).

Conclusion: In summary, our meta-analysis found strong associations between GSTP1 and P16 gene promoter methylation and an increased HBV-related HCC susceptibility. Moreover, GSTP1 and P16 methylation in promoter region could obviously increase the risk of HBV-related HCC in patients with cirrhosis, indicating that these would be promising biomarkers for early clinical diagnosis of HBV-related HCC.

Keywords: GSTP1; Hepatitis B virus; P16; hepatocellular carcinoma; meta-analysis.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Flow diagram of search strategy and study selection for meta-analysis.
Figure 2
Figure 2
Forest plots of GSTP1 promoter region methylation and the risk of HBV-related HCC. Notes: (A) Neoplasm vs normal tissues; (B) neoplasm vs cirrhosis tissues. Each square represents an OR for each specific study, with square sizes proportional to the weight. Weights are from random-effects analysis. Abbreviations: GSTP1, glutathione-S-transferase Pi 1; HBV, hepatitis B virus; HCC, hepatocellular carcinoma.
Figure 3
Figure 3
Forest plots of P16 promoter region methylation and the risk of HBV-related HCC. Notes: (A) Neoplasm vs adjacent tissues; (B) neoplasm vs normal tissues; (C) neoplasm vs cirrhosis tissues; (D) neoplasm vs CHB tissues. Each square represents an OR for each specific study, with square sizes proportional to the weight. Weights are from random-effects analysis. Abbreviations: CHB, chronic hepatitis B; HBV, hepatitis B virus; HCC, hepatocellular carcinoma.
Figure 4
Figure 4
Begg’s funnel plot analysis for publication bias between GSTP1 methylation and HBV-related HCC susceptibility. Notes: (A) Neoplasm vs normal tissues; (B) neoplasm vs cirrhosis tissues. Abbreviations: GSTP1, glutathione-S-transferase Pi 1; HBV, hepatitis B virus; HCC, hepatocellular carcinoma.
Figure 5
Figure 5
Begg’s funnel plot analysis for publication bias between P16 methylation and HBV-related HCC susceptibility. Notes: (A) Neoplasm vs adjacent tissues; (B) neoplasm vs normal tissues; (C) neoplasm vs cirrhosis tissues; (D) neoplasm vs CHB tissues. Abbreviations: CHB, chronic hepatitis B; HBV, hepatitis B virus; HCC, hepatocellular carcinoma.
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