title: HIF-1 alpha overexpression correlates with poor overall survival and disease-free survival in gastric cancer patients post-gastrectomy.
abstract: 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-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.
  
  
  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-β, HIF-1α, VEGF and pERK1/2 were determined. Long-term survival of these patients was analyzed using univariate and multivariate analyses.
  
  
  RESULTS
  HIF-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).
  
  
  CONCLUSIONS
  HIF-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.
authors.affiliation: Department of Comprehensive Treatment Oncology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Comprehensive Treatment Oncology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Pathology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Comprehensive Treatment Oncology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Comprehensive Treatment Oncology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Qin
authors.affiliation: Department of Comprehensive Treatment Oncology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Surgical oncology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Baoqing
authors.initials: B
authors.lastname: Jia
authors.affiliation: Department of General surgery, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wei
authors.affiliation: Department of Pathology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Comprehensive Treatment Oncology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Guanghai
authors.initials: G
authors.lastname: Dai
authors.affiliation: Department of Medical oncology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Shunchang
authors.initials: S
authors.lastname: Jiao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005743:Gastrectomy; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018719:Erb-b2 Receptor Tyrosine Kinases; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C508053:ERBB2 protein, human