title: Clinical significance of hypoxia-inducible factor 1 and VEGF-A in osteosarcoma.
abstract: BACKGROUND
  Although the function of hypoxia-inducible factor 1 (HIF1) in many kinds of solid tumor has been revealed, the significance of HIF1 in osteosarcoma is still controversial and not well understood.
  
  
  METHODS
  Immunohistochemistry was used to detect HIF1 expression. The correlation between HIF1 and clinicopathology factors was analyzed by use of chi-squared tests. The prognostic value of HIF1 was evaluated by univariate and multivariate analysis. Moreover, the function of HIF1 in osteosarcoma cells was further investigated in in-vitro experiments by regulating HIF1 and vascular endothelial growth factor-A (VEGF-A) expression.
  
  
  RESULTS
  Expression of HIF1 was high for 56.82 % of the samples in our investigation. HIF1 expression was significantly associated with positive metastasis (P = 0.037). By use of the Kaplan-Meier method, high expression of HIF1 was proved to be related to poorer overall survival (P = 0.007). By use of a Cox-regression model, HIF1 was identified as an independent prognostic biomarker (P = 0.019). We also proved that HIF1 can promote osteosarcoma invasion in hypoxia by inducing VEGF-A expression.
  
  
  CONCLUSIONS
  HIF1 was identified as an independent prognostic biomarker in osteosarcoma. It can promote osteosarcoma cell invasion by inducing VEGF-A expression, indicating that HIF1 is a potential drug target in osteosarcoma.
authors.affiliation: Department of Orthopedics, Linyi People's Hospital, Linyi, 276003, China.
authors.forename: Huanli
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, Linyi People's Hospital, Linyi, 276003, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Linyi People's Hospital, Linyi, 276003, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Surgery, Linyi People's Hospital, Linyi, 276003, Shangdong Province, China. bradforly@163.com.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Liu
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001859:Bone Neoplasms / Q000737:chemistry* / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000737:chemistry* / Q000556:secondary*; D011379:Prognosis; D016016:Proportional Hazards Models; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D051793:Hypoxia-Inducible Factor 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Hypoxia-inducible factor 1; Invasion; Osteosarcoma; Prognosis; VEGF-A