Association between APC promoter methylation and clinicopathological features of patients with hepatocellular carcinoma: a meta-analysis with PRISMA guideline

Background: The adenomatous polyposis coli (APC) has been reported as a key tumor suppressor gene in hepatocellular carcinoma (HCC). However, the clinical significance of APC promoter methylation in HCC remains unclear. This meta-analysis was conducted to assess the relationship between APC promoter methylation and clinicopathological characteristics of patients with HCC. Methods: Eligible publications were identified by online electronic databases (PubMed, Embase, EBSCO and the Cochrane Library). The combined odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were calculated and summarized under the random-effects model. Results: Final 21 available studies were included in the current study. APC promoter methylation was significantly higher in HCC than in normal live tissues, liver cirrhosis, and healthy blood samples (OR =11.46, P<0.001; OR =6.04, P<0.001; OR =93.83, P<0.001;respectively). No significant correlation was found between HCC and chronic hepatitis, and dysplastic nodules (P>0.1). APC promoter methylation was shown to be associated with hepatitis B virus (HBV), and hepatitis C virus (HCV) infection status of patients with HCC (OR =2.86, P=0.005; OR =3.50, P=0.001; respectively), but not correlated with clinical stage, gender, and vascular invasion status (P>0.1). Conclusions: APC promoter methylation may be correlated with HCC, especially for patients with HBV and HCV infection status. Promoter methylation of the APC may be a potential noninvasive biomarker using blood samples in the detection of HCC. More studies with large samples sizes are needed to validate our findings in the future.