Hypoxia inducible factor-1alpha (HIF-1alpha) was well correlated with carcinogenesis and tumor progression in many kinds of cancer. In this study, high expression of HIF-1alpha 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-1alpha had a significantly shorter overall survival rate and disease-free survival rate than those with low expression. Multivariate analysis showed high HIF-1alpha expression was a borderline independent factor of overall survival. HIF-1alpha expression was also found to be significantly correlated with the expression of hepatitis B virus X protein (HBx), and over-expressed HBx upregulated HIF-1alpha protein expression in vitro. These results suggested that HIF-1alpha, which was partially regulated by HBx, might be a prognostic marker of HBV-related HCC patients.
Gankyrin, a small and highly conserved protein which is identical to the p28 gene product, was found to be related with the malignant phenotypes in liver and esophageal carcinoma. However, the roles of gankyrin in colorectal carcinoma (CRC) are still unknown. In the present study, the gankyrin mRNA and protein expression in human CRC cell lines and clinical tissue samples were evaluated and correlated with clinicopathological features. Possible mechanisms by which gankyrin regulates the malignant phenotype of CRC cells were also investigated. The results demonstrated that gankyrin was obviously overexpressed in CRC tissues and cell lines compared to controls, and gankyrin expression was correlated with TNM stages and metastasis of CRC. Overexpression of gankyrin by PhkitNeo-hGankyrin plasmid transfected into Lovo cells could promote the cell proliferation and tumorigenicity. This finding was further strengthened by experiments that suppressing gankyrin expression by siRNA exerted the opposite effects on CRC cells SW620. In addition, our present study showed that the co-expression of cyclinD1 and beta-catenin were positive correlation with the alteration of gankyrin expression. This data suggested that gankyrin played significant roles in the pathogenesis of human CRC, and might be an important therapeutic target for CRC.
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