title: Clinicopathological characteristics of gynecological cancer associated with hypoxia-inducible factor 1α expression: a meta-analysis including 6,612 subjects.
abstract: BACKGROUND
  Gynecological cancer is characterized by tumor hypoxia. However, the role of hypoxia-inducible factor 1α (HIF-1α) in gynecological cancer remains unclear.
  
  
  METHODS
  Electronic databases including Cochrane Library, PUBMED, Web of Knowledge and clinical trial registries were searched from inception through October 2014 for published, case-control studies assessing the association between HIF-1α and the clinicopathological characteristics of gynecological cancer. We pooled results from 59 studies using fixed or random-effects models and present results as odds ratios (ORs) following the PRISMA guidelines.
  
  
  RESULTS
  Our meta-analysis, which included 6,612 women, demonstrated that the expression of HIF-1α was associated with the clinicopathological characteristics of gynecological cancer. The expression of HIF-1α in cancer or borderline tissue was significantly higher than that in normal tissue (cancer vs. normal: odds ratio (OR) =9.59, 95% confidence interval (CI): 5.97, 15.39, p<0.00001; borderline vs. normal: OR=4.13, 95% (CI): 2.43, 7.02, p<0.00001; cancer vs. borderline: OR=2.70, 95% (CI): 1.69, 4.31, p<0.0001). The expression of HIF-1α in III-IV stage or lymph node metastasis was significantly higher than that in I-II stage or that without lymph node metastasis, respectively (OR=2.66, 95% (CI): 1.87,3.79, p<0.00001; OR= 3.98, 95% (CI): 2.10,12.89, p<0.0001). HIF-1α was associated with histological grade of cancer (Grade 3 vs. Grade 1: OR=3.77, 95% (CI): 2.76,5.16, p<0.00001; Grade 3 vs. Grade 2: OR=1.62, 95% (CI): 1.20,2.19, p=0.002; Grade 2 vs. Grade 1: OR=2.34, 95% (CI): 1.82,3.00, p<0.00001),5-years disease free survival (DFS) rates (OR=2.93, 95% (CI):1.43,6.01, p=0.001) and 5-years overall survival (OS) rates (OR=5.53, 95% (CI): 2.48,12.31, p<0.0001).
  
  
  CONCLUSIONS
  HIF-1α is associated with the malignant degree, FIGO stage, histological grade, lymph node metastasis, 5-years survival rate and recurrence rate of gynecological cancer. It may play an important role in clinical treatment and prognostic evaluation.
authors.affiliation: Department of Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Therapeutics Research Centre, Princess Alexandra Hospital, School of Medicine, The University of Queensland, Brisbane, Australia.
authors.forename: Haolu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ma
authors.affiliation: Therapeutics Research Centre, Princess Alexandra Hospital, School of Medicine, The University of Queensland, Brisbane, Australia.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liang
authors.affiliation: Therapeutics Research Centre, Princess Alexandra Hospital, School of Medicine, The University of Queensland, Brisbane, Australia.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
mesh_terms: D005260:Female; D005833:Genital Neoplasms, Female / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit