Abstract
BackgroundOverall, gastric cancer prognosis remains poor. Detailed characterization of molecular markers that govern gastric cancer pathogenesis is warranted to establish innovative therapeutic options. HIF-1α overexpression has been linked to poor gastric cancer prognosis. However, though researched for years, the prognostic role of HIF-1α in gastric cancer is still controversial. Hence, the objective of the present study was to analyze the prognostic values of HIF-1α, TGF-β, VEGF and pERK1/2 in gastric cancer patients following gastrectomy.MethodsThis 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-β, HIF-1α, VEGF and pERK1/2 were determined. Long-term survival of these patients was analyzed using univariate and multivariate analyses.ResultsHIF-1α overexpression was more frequent in patients with hepatic metastases (71.6% versus 43.0% in those without hepatic metastases, P = 0.000, χ2 = 23.086) and more frequent in patients with peritoneum cavity metastasis (62.3% versus 43.0% in those without such metastasis, P = 0.000, χ2 = 13.691). In univariate analysis, patients with HIF-1α 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, χ2 = 74.937; OS: NA VS. 25.5 m, P = 0.000, χ2 = 90.594). Importantly, HIF-1α 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).ConclusionsHIF-1α 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-1α expression can be used to stratify patients at higher risk for poor prognosis, and is potentially an important therapeutic target in gastric cancer patients.
Highlights
Gastric cancer (GC) is one of the most common malignancies in the world
hypoxia inducible factor-1 alpha (HIF-1a) was expressed in tumor cell nuclei (Fig. 1C and 1D). pERK1/2 was observed both in tumor cell cytoplasm and nuclei (Fig. 1G and 1H)
HIF-1a overexpression was more frequent in patients with hepatic metastases (71.6% versus 43.0% in those without hepatic metastases, P = 0.000, x2 = 23.086) and was more frequent in patients with peritoneum cavity metastasis (62.3% versus 43.0% in those without peritoneum cavity metastasis, P = 0.000, x2 = 13.691)
Summary
Gastric cancer (GC) is one of the most common malignancies in the world. Due to lack of specific early symptoms or effective tumor biomarkers, most patients with GC are not diagnosed until advanced stages. It is critical to identify specific markers and develop novel therapeutic strategies for advanced and recurrent gastric cancer. Local tumor recurrence and distal metastasis are both dependent on neovascularization, which is regulated through angiogenesis factors. Several of these factors have been found to play an important role in regulating tumor angiogenesis, and are up regulated concomitantly with rapid growth and early metastasis [3]. HIF-1a overexpression has been linked to poor gastric cancer prognosis. Though researched for years, the prognostic role of HIF-1a in gastric cancer is still controversial. The objective of the present study was to analyze the prognostic values of HIF-1a, TGF-b, VEGF and pERK1/2 in gastric cancer patients following gastrectomy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
