title: High expression of HIF1a is a predictor of clinical outcome in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA, VEGF, and bFGF.
abstract: OBJECTIVE
  Pancreatic cancer still has one of the worst prognoses in gastrointestinal cancers with a 5-year survival rate of 5%, making it necessary to find markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens. In this study, we investigated the prognostic values of HIF1a, bFGF, VEGF, and PDGFA gene expressions as well as their interrelationships.
  
  
  METHODS
  Formalin-fixed paraffin-embedded tissue samples were obtained from 41 patients with pancreatic adenocarcinoma (age, 65; range, 34-85 years). After laser capture microdissection, direct quantitative real-time reverse transcription-polymerase chain reaction assays were performed in triplicates to determine HIF1a, PDGFA, VEGF, and bFGF gene expression levels. Multivariate Cox proportional hazards regression analysis was used to assess the impact of HIF1a gene expression on prognosis.
  
  
  RESULTS
  HIF1a was significantly correlated to every gene we tested: bFGF (P = .04), VEGF (P = .02), and PDGFA (P = .03). Tumor size, P = .04, and high HIF1a mRNA expression (cutoff, 75th percentile) had a significant impact on survival, P = .009 (overall model fit, P = .02). High HIF1a expression had a sensitivity of 87.1% and a specificity of 55.6% for the diagnosis short (<6 months) versus long (6-60 months) survival.
  
  
  CONCLUSIONS
  Measuring PDGFA, bFGF, and HIF1a expression may contribute to a better understanding of the prognosis of patients with pancreatic cancer and may even play a crucial role for the distribution of patients to multimodal therapeutic regimens. Larger studies including patients treated with actual chemotherapeutics seem to be warranted.
authors.affiliation: Department of Biochemistry and Molecular Biology and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA. ach@o117.com
authors.forename: Andreas-Claudius
authors.initials: AC
authors.lastname: Hoffmann
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Mori
authors.forename: Daniel
authors.initials: D
authors.lastname: Vallbohmer
authors.forename: Jan
authors.initials: J
authors.lastname: Brabender
authors.forename: Ellen
authors.initials: E
authors.lastname: Klein
authors.forename: Uta
authors.initials: U
authors.lastname: Drebber
authors.forename: Stephan E
authors.initials: SE
authors.lastname: Baldus
authors.forename: Janine
authors.initials: J
authors.lastname: Cooc
authors.forename: Mizutomo
authors.initials: M
authors.lastname: Azuma
authors.forename: Ralf
authors.initials: R
authors.lastname: Metzger
authors.forename: Arnulf H
authors.initials: AH
authors.lastname: Hoelscher
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Danenberg
authors.forename: Klaus L
authors.initials: KL
authors.lastname: Prenzel
authors.forename: Peter V
authors.initials: PV
authors.lastname: Danenberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011379:Prognosis; D016019:Survival Analysis; D015854:Up-Regulation; D042442:Vascular Endothelial Growth Factors / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010982:Platelet-Derived Growth Factor; D042442:Vascular Endothelial Growth Factors; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2