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. 2008 Jul;10(7):674-9.
doi: 10.1593/neo.08292.

High expression of HIF1a is a predictor of clinical outcome in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA, VEGF, and bFGF

Andreas-Claudius Hoffmann  1 , 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
Affiliations

High expression of HIF1a is a predictor of clinical outcome in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA, VEGF, and bFGF

Andreas-Claudius Hoffmann et al. Neoplasia. 2008 Jul.

Abstract

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 (<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.

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Figures

Figure 1
Figure 1
Scatterplot of the log-transformed ΔCt values for the studied genes. The lines represent the cutoff values based on recursive descent partition analysis.
Figure 2
Figure 2
Kaplan-Meier plot, estimating overall survival and relapsefree survival. Differences in survival between the high and the low bFGF expression groups were analyzed with the log rank test.
Figure 3
Figure 3
Kaplan-Meier plot, estimating overall survival and relapse-free survival. Differences in survival between the high and the low PDGFA expression groups were analyzed with the log rank test.
Figure 4
Figure 4
Survival plot from multivariate Cox regression analysis estimating overall survival and relapse-free survival. The upper light gray line represents the patients with a HIF1a expression of lower than the 75th percentile.
See this image and copyright information in PMC

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