title: Prognostic value and clinicopathological differences of HIFs in colorectal cancer: evidence from meta-analysis.
abstract: BACKGROUND
  The prognostic value of HIFs in colorectal cancer was evaluated in a large number of studies, but the conclusions were inconclusive. Meanwhile, clinicopathologic differences of HIF-1α and HIF-2α were rarely compared in recent studies.
  
  
  METHODS
  Identical search strategies were used to search relevant literatures in the PubMed and Web of Science databases. The prognostic significances and clinicopathological differences of HIFs in CRC were analyzed.
  
  
  RESULTS
  A total of 23 studies comprising 2984 CRC patients met the inclusion criteria. The results indicated that overexpressed HIFs were significantly associated with increase of mortality risk, including overall survival (OS) (HR 2.06 95%CI 1.55-2.74) and disease free survival (HR 2.84, 95%CI 1.87-4.31). Subgroup analysis revealed that both overexpressed HIF-1α and HIF-2α had correlations with worse prognosis. The pooled HRs were 2.01 (95% CI: 1.55-2.6) and 2.07(95% CI: 1.01-4.26). Further subgroup analysis on HIF-1α was performed by study location, number of patients, quality score and cut-off value. The results showed that HIF-1α overexpression was significantly associated with poor OS, particularly in Asian countries (HR 2.3, 95% CI: 1.74-3.01), while not in European or other countries. In addition, overexpression of HIF-1α was closely related with these clinicopathological features, including Dukes' stages (OR 0.39, 95% CI: 0.17-0.89), UICC stages (OR 0.42 95% CI: 0.3-0.59), depth of invasion (OR 0.71, 95% CI: 0.51-0.99), lymphnode status (OR 0.49, 95% CI: 0.32-0.73) and metastasis (OR 0.29, 95% CI: 0.11-0.81). While overexpression of HIF-2α was only associated with grade of differentiation (OR 0.48, 95% CI: 0.29-0.81).
  
  
  CONCLUSIONS
  This study showed that both HIF-1α and HIF-2α overexpression were associated with an unfavorable prognosis. HIF-1α overexpression seemed to be associated with worse prognosis in Asian countries. Additionally, HIF-1α and HIF-2α indicated distinct clinicopathologic features.
authors: Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China ; Cancer Institute (Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences), Zhejiang University School of Medicine, Hangzhou, China.
authors: Zhigang
authors: Z
authors: Chen
authors: Xin
authors: X
authors: He
authors: Wenjie
authors: W
authors: Xia
authors: Qi
authors: Q
authors: Huang
authors: Zhigang
authors: Z
authors: Zhang
authors: Jun
authors: J
authors: Ye
authors: Chao
authors: C
authors: Ni
authors: Pin
authors: P
authors: Wu
authors: Dang
authors: D
authors: Wu
authors: Jinghong
authors: J
authors: Xu
authors: Fuming
authors: F
authors: Qiu
authors: Jian
authors: J
authors: Huang
mesh_terms: D044466:Asian People; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D016206:Databases, Bibliographic; D015870:Gene Expression; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D060787:Neoplasm Grading; D016017:Odds Ratio; D011379:Prognosis; D012306:Risk; D016019:Survival Analysis; D044465:White People; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human