HIF-1 Alpha Overexpression Correlates with Poor Overall Survival and Disease-Free Survival in Gastric Cancer Patients Post-Gastrectomy

Background: Overall, gastric cancer prognosis remains poor. Detailed characterization of molecular markers that govern gastric cancer pathogenesis is warranted to establish innovative therapeutic options. HIF-1 alpha overexpression has been linked to poor gastric cancer prognosis. However, though researched for years, the prognostic role of HIF-1 alpha in gastric cancer is still controversial. Hence, the objective of the present study was to analyze the prognostic values of HIF-1 alpha, TGF-beta, VEGF and pERK1/2 in gastric cancer patients following gastrectomy. Methods: This study included 446 patients with confirmed gastric cancer who underwent gastrectomy in a single Chinese Cancer Center between 2005 and 2006. Clinicopathologic features, as well as immunohistochemical analysis of TGF-beta, HIF-1 alpha, VEGF and pERK1/2 were determined. Long-term survival of these patients was analyzed using univariate and multivariate analyses. Results: HIF-1 alpha overexpression was more frequent in patients with hepatic metastases (71.6% versus 43.0% in those without hepatic metastases, P = 0.000, chi(2) = 23.086) and more frequent in patients with peritoneum cavity metastasis (62.3% versus 43.0% in those without such metastasis, P = 0.000, chi(2) = 13.691). In univariate analysis, patients with HIF-1 alpha overexpression had a shorter disease-free survival (DFS) and overall survival (OS) than patients with weak-expression (DFS: NA VS. 16.8 m, P = 0.000, chi(2) = 74.937; OS: NA VS. 25.5 m, P = 0.000, chi(2) = 90.594). Importantly, HIF-1 alpha overexpression was a promising prognostic marker for poor survival by multivariate analysis (DFS: HR 2.766, 95% CI 2.136-2.583, P = 0.000; OS: HR 3.529, 95% CI 2.663-4.667, P = 0.000). Conclusions: HIF-1 alpha overexpression could be considered a useful independent prognostic biomarker in gastric cancer after gastrectomy, and is correlated to both a poor overall survival and disease-free survival in these patients. HIF-1 alpha expression can be used to stratify patients at higher risk for poor prognosis, and is potentially an important therapeutic target in gastric cancer patients.