High Expression of HIF1a Is a Predictor of Clinical Outcome in Patients with Pancreatic Ductal Adenocarcinomas and Correlated to PDGFA, VEGF, and bFGF

Autor: Andreas-Claudius Hoffmann, Ryutaro Mori, Daniel Vallbohmer, Jan Brabender, Ellen Klein, Uta Drebber, Stephan E. Baldus, Janine Cooc, Mizutomo Azuma, Ralf Metzger, Arnulf H. Hoelscher, Kathleen D. Danenberg, Klaus L Prenzel, Peter V. Danenberg
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Zdroj: Neoplasia: An International Journal for Oncology Research, Vol 10, Iss 7, Pp 674-679 (2008)
Druh dokumentu: article
ISSN: 1476-5586
1522-8002
DOI: 10.1593/neo.08292
Popis: PURPOSE: 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. EXPERIMENTAL DESIGN: 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 (
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