Association of hypoxia-inducible factor 1α expression with susceptibility to hepatitis B virus-related hepatocellular carcinoma: A meta-analysis

Hypoxia-inducible factor 1 alpha (HIF-1 alpha) triggers tumorigenesis and progression in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Inconsistent findings have been reported on the influence of HIF-1 alpha over-expression on the clinical outcomes of HBV-related HCC. This study aims to clarify the role of HIF-1 alpha overexpression in the tumorigenesis and prognosis of HBV-induced HCC. Systematic and comprehensive search of online papers was carried out to elucidate the contribution of HIF-1 alpha expression to susceptibility of HBV-induced HCC. STATA 12.0 software was utilized to analyze available data extracted from all eligible literature. Publication bias and sensitivity were comprehensively analyzed. A total of 23 published studies involving 2244 subjects were finally screened. The HIF-1 alpha expression was remarkably upregulated in HBV-induced HCC tissues than in normal liver tissues, non-tumorous tissues, paraneoplastic tissues, and non-HBV HCC tissues. The high HIF-1 alpha expression tended to be positively related to capsular infiltration (odds ratio (OR) 1.767; 95% confidence interval (CI) 1.058, 2.950). The HIF-1 alpha expression was relevant to lymph node metastasis (OR 3.778; 95% CI 1.666, 8.568). High levels of HIF-1 alpha expression tended to be closely implicated in portal vein invasion (OR 6.728, 95% CI 2.191, 20.656) but were irrelevant to alpha-fetoprotein, cirrhosis, Edmondson grading, tumor size, age, gender, and histological grade. Analysis of pooled data showed that HIF-1 alpha was not statistically relevant to poor overall survival in HBV-related HCC. Our data provides compelling evidence that HIF-1 alpha overexpression may imply a greater probability of invasion and metastasis in patients with HBV-induced HCC.