Expressions of hypoxia-inducible factor-1α and hexokinase-II in gastric adenocarcinoma: the impact on prognosis and correlation to clinicopathologic features

The impact of hypoxia-inducible factor (HIF)-1 alpha and hexokinase-II (HK-II) expression on prognosis of gastric adenocarcinoma patients has not been clearly established. We identified all patients in Cancer Center of Sun Yat-Sen University who were diagnosed as gastric adenocarcinoma and underwent radical gastrectomy between January 1999 and December 2001. We used immunohistochemistry to determine the expressions of HIF-1 alpha protein and HK-II in the surgical sections. We identified 188 patients with gastric adenocarcinoma for the final analysis. The positive rate of HIF-1 alpha and HK-II were 110/188 (54.6%) and 40/188 (21.3%), respectively. Both HIF-1 alpha and HK-II were all positively correlated with tumor size, lower differentiation, and tumor stage. Univariate analysis showed that advanced tumor stages (P < 0.001), tumor size (P = 0.003), HIF-1 alpha expression (P < 0.001), and HK-II expression (P < 0.001) were all significantly associated with shorter survival. The multivariate Cox analysis revealed that tumor stage (P < 0.001), HIF-1 alpha expression (P < 0.001), and HK-II expression (P = 0.002) remained independent prognostic variables for survival. In addition, there was a positive correlation of HIF-1 alpha protein expression and HK-II (P = 0.022). Both HIF-1 alpha and HK-II were overexpressed in gastric adenocarcinoma. The multivariate Cox analysis revealed that both of them were independent factors on survival of gastric adenocarcinoma patients.