title: Association of elevated HIF-2α levels with low Beclin 1 expression and poor prognosis in patients with chondrosarcoma.
abstract: BACKGROUND
  Hypoxia inducible factor (HIF)-2α is an important transcription factor that contributes to tumor proliferation and progression. Beclin 1 is a key mediator of autophagy, and dysfunction of Beclin 1 is implicated in tumorigenicity. This study was designed to investigate the expression patterns of HIF-2α and Beclin 1 and to clarify their clinical significance in chondrosarcoma.
  
  
  METHODS
  The mRNA and protein levels of HIF-2α and Beclin 1 in chondrosarcoma and the corresponding nontumor tissues were analyzed by real-time polymerase chain reaction and Western blot, respectively. The protein expression of HIF-2α and Beclin 1 was investigated by immunohistochemistry, and their associations with clinicopathological factors and overall survival were evaluated.
  
  
  RESULTS
  HIF-2α was remarkably elevated, whereas Beclin 1 was significantly reduced in chondrosarcoma compared with the corresponding nontumor tissues. High HIF-2α level and negative Beclin 1 expression were 52.9% and 58.8% in chondrosarcoma specimens, respectively. HIF-2α and Beclin 1 were associated with histological grade and Musculoskeletal Tumor Society stage. There was a significant inverse relationship between HIF-2α and Beclin 1. HIF-2α and Beclin 1 had significant impacts on the prognosis of chondrosarcoma patients. Multivariate analysis revealed that Beclin 1 was an independent prognostic factor for overall survival of patients with chondrosarcoma.
  
  
  CONCLUSIONS
  Elevated HIF-2α levels associated with low Beclin 1 expression play a role in the development of chondrosarcoma. Beclin 1 can serve as a novel biomarker to predict survival of chondrosarcoma patients, and may represent a potential therapeutic target.
authors.affiliation: Department of Orthopaedic Surgery, Tianjin Hospital, Tianjin, China.
authors.forename: Changbao
authors.initials: C
authors.lastname: Chen
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Ma
authors.forename: Xinlong
authors.initials: X
authors.lastname: Ma
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Liu
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Liu
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D000071186:Beclin-1; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002813:Chondrosarcoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D000071186:Beclin-1; D008565:Membrane Proteins; D012333:RNA, Messenger; D000099162:Endothelial PAS Domain-Containing Protein 1; C491997:BECN1 protein, human