The Expression of Hypoxia-Inducible Factor-1 alpha in Hepatitis B Virus-Related Hepatocellular Carcinoma: Correlation with Patients' Prognosis and Hepatitis B Virus X Protein

Hypoxia inducible factor-1 alpha (HIF-1 alpha) was well correlated with carcinogenesis and tumor progression in many kinds of cancer. In this study, high expression of HIF-1 alpha was found in 37 of the 72 (51.39%) tumor specimens, and significantly correlated with venous invasion and lymphonode invasion. Patients with high expression of HIF-1 alpha had a significantly shorter overall survival rate and disease-free survival rate than those with low expression. Multivariate analysis showed high HIF-1 alpha expression was a borderline independent factor of overall survival. HIF-1 alpha expression was also found to be significantly correlated with the expression of hepatitis B virus X protein (HBx), and over-expressed HBx upregulated HIF-1 alpha protein expression in vitro. These results suggested that HIF-1 alpha, which was partially regulated by HBx, might be a prognostic marker of HBV-related HCC patients.