title: The correlation of expression levels of HIF-1α and HIF-2α in hepatocellular carcinoma with capsular invasion, portal vein tumor thrombi and patients' clinical outcome.
abstract: OBJECTIVE
  The roles of hypoxia-inducible factor-1α and hypoxia-inducible factor-2α in the development of hepatocellular carcinoma have not been fully elucidated. Here, we aim to uncover the relationship between the prognosis of hepatocellular carcinoma patients and the expression of hypoxia-inducible factor-1α and hypoxia-inducible factor-2α in tumor tissues.
  
  
  METHODS
  The protein levels of hypoxia-inducible factor-1α and hypoxia-inducible factor-2α were detected by immunohistochemistry on paraffin sections of 126 paired hepatocellular carcinoma tissue and peritumoral tissue samples. The mRNA levels of them were detected by quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  High expression of hypoxia-inducible factor-1α was found in 57.1% (72/126) of tumor specimens, compared with 5.6% (7/126) in peritumoral tissues, while high expression of hypoxia-inducible factor-2α was found in only 13.5% (17/126) of tumors, compared with 47.6% (60/126) of peritumoral tissues. There was high expression of hypoxia-inducible factor-1α protein in hepatocellular carcinoma tissues closely associated with capsular infiltration and portal vein invasion, and thus lower overall survival and disease-free survival of hepatocellular carcinoma patients (P < 0.05). No significant association has been found between the expression of hypoxia-inducible factor-2α protein and capsular infiltration, portal vein invasion, overall survival and disease-free survival (P > 0.05). However, patients with high expression of both hypoxia-inducible factor-1α and hypoxia-inducible factor-2α have a significantly worse outcome than patients with low expression of both hypoxia-inducible factor-1α and hypoxia-inducible factor-2α (P < 0.05).
  
  
  CONCLUSIONS
  The discordant results on expression of hypoxia-inducible factor-1α and hypoxia-inducible factor-2α suggest that these two proteins are differentially regulated in vivo, thus reflecting distinctive protein expression and stabilization mechanisms. The association between hypoxia-inducible factor-1α expression and unfavorable outcome indicates the importance of using hypoxia-inducible factor-1α as a treatment target in hepatocellular carcinoma.
authors.affiliation: *Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550001, China. jjx731003@163.com.
authors.forename: Sheng-Li
authors.initials: SL
authors.lastname: Yang
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Liu
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Jiang
authors.forename: Zhi-Fan
authors.initials: ZF
authors.lastname: Xiong
authors.forename: Qian-Jin
authors.initials: QJ
authors.lastname: He
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis* / Q000235:genetics; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000737:chemistry; D008113:Liver Neoplasms / Q000737:chemistry* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009360:Neoplastic Cells, Circulating; D011169:Portal Vein; D011237:Predictive Value of Tests; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome; 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
keywords: HIF-1α; HIF-2α; disease-free survival; hepatocellular carcinoma; overall survival