title: Clinical and prognostic significance of HIF-1α, PTEN, CD44v6, and survivin for gastric cancer: a meta-analysis.
abstract: OBJECTIVE
  This study was to quantitatively summarize published data for evaluating the clinical and prognostic significance of four proteins involved in hypoxia-inducible factor-1 (HIF-1α) regulation of the metastasis cascade.
  
  
  METHODS
  Searches were performed using the MEDLINE, EMBASE, Cochrane Library, and Chinese Biomedicine databases without any language restrictions. Studies were pooled and either the summary risk ratio (RR) or odds ratio (OR) was calculated. Potential sources of heterogeneity were sought out via subgroup and sensitivity analyses, and publication bias was also performed.
  
  
  RESULTS
  Seventeen studies evaluated HIF-1α, 20 studies evaluated phosphatase and tensin homolog (PTEN), 20 studies evaluated Survivin, and 16 studies evaluated CD44v6. Our results showed that increased HIF-1α expression was linked to a poor 5-year overall survival (RR = 1.508; 95% confidence interval (CI) 1.318-1.725; P<0.001). Decreased survival was heavily influenced by advanced tumor invasion (OR = 3.050; 95% CI 2.067-4.501; P<0.001), lymph node metastasis (1415 patients; OR = 3.486, 95% CI 2.737-4.440; P<0.001), distant metastasis (OR = 6.635; 95% CI 1.855-23.738; P = 0.004), vascular invasion (OR = 2.368; 95% CI 1.725-3.252; P<0.001), dedifferentiation (OR = 2.112; 95% CI 1.410-3.163; P<0.001), tumor size (OR = 1.921; 95% CI 1.395-2.647; P<0.001), and a higher TNM stage (OR =  2.762; 95% CI 1.941-3.942; P<0.001). Similarly, aberrant expression of PTEN, CD44v6, and Survivin were also observed in tumors that correlated with poor OS. The higher ORs of death at 5 years were 1.637 (95% CI = 1.452-1.845; P<0.001), 1.901 (95% CI = 1.432-2.525; P<0.001), and 1.627 (95% CI = 1.384-1.913; P<0.001), respectively, with an OR>2 for the main stratified meta-analyses of clinical factors.
  
  
  CONCLUSIONS
  Our findings indicate that HIF-1α/PTEN/CD44v6/Survivin, as measured by immunohistochemistry, can be used to predict the prognosis and potential for invasion and metastasis in Asian patients with gastric cancer. The development of strategies against this subset of proteins could lead to new therapeutic approaches.
authors.affiliation: Department of Medical Genetic and Cell Biology, Ningxia Medical University, Yinchuan, China; Key Laboratory of Fertility Preservation and Maintenance (Ningxia Medical University), Ministry of Education, Yinchuan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Oncology, General Hospital of the Ningxia Medical University, Yinchuan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Oncology, General Hospital of the Ningxia Medical University, Yinchuan, China.
authors.forename: Qilun
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Medical Genetic and Cell Biology, Ningxia Medical University, Yinchuan, China; Key Laboratory of Fertility Preservation and Maintenance (Ningxia Medical University), Ministry of Education, Yinchuan, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Jiao
authors.affiliation: Department of Medical Genetic and Cell Biology, Ningxia Medical University, Yinchuan, China; Key Laboratory of Fertility Preservation and Maintenance (Ningxia Medical University), Ministry of Education, Yinchuan, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Medical Genetic and Cell Biology, Ningxia Medical University, Yinchuan, China; Key Laboratory of Fertility Preservation and Maintenance (Ningxia Medical University), Ministry of Education, Yinchuan, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Medical Genetic and Cell Biology, Ningxia Medical University, Yinchuan, China; Key Laboratory of Fertility Preservation and Maintenance (Ningxia Medical University), Ministry of Education, Yinchuan, China.
authors.forename: Zhenghao
authors.initials: Z
authors.lastname: Huo
mesh_terms: D015687:Cell Hypoxia; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011379:Prognosis; D017594:Publication Bias; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D016019:Survival Analysis; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; C112697:CD44v6 antigen; C497442:HIF1A protein, human; D018960:Hyaluronan Receptors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human