High expression of HIF1a is a predictor of clinical outcome in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA, VEGF, and bFGF
High expression of HIF1a is a predictor of clinical outcome in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA, VEGF, and bFGF
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DOI：
10.1593/neo.08292
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发表时间：
2008-07-01
期刊：
影响因子：
4.8
通讯作者：
Danenberg, Peter V.
中科院分区：
文献类型：
--
作者：
Hoffmann, Andreas-Claudius;Mori, Ryutaro;Danenberg, Peter V.
目的：胰腺癌仍是胃肠道肿瘤中预后最差的肿瘤之一，其5年生存率为5%，因此有必要寻找能进一步将患者分为不同危险类别的标志物或基因集，从而允许更多的个体化、多模式的治疗方案。在本研究中，我们研究了HIF1a、bFGF、VEGF和PDGFA基因表达的预后价值以及它们之间的相互关系。实验设计：取自41例胰腺癌患者的福尔马林固定石蜡包埋组织标本，年龄65岁，年龄34~85岁。激光捕获显微切割后，采用直接实时定量逆转录-聚合酶链式反应检测HIF1a、PDGFA、VEGF和bFGF基因的表达水平。多因素COX比例风险回归分析HIF1a基因表达对预后的影响。结果：HIF1a与我们检测的每一个基因显著相关：bFGF(P=0.04)、VEGF(P=0.02)和PDGFA(P=0.03)。肿瘤大小(P=0.04)和HIF1a高表达(第75个百分位数)对生存率有显著影响，P=0.009(总体模型拟合，P=0.02)。HIF1a高表达对判断生存期短(6个月)与长(6-60个月)的敏感性为87.1%，特异性为55.6%。结论：检测PDGFA、bFGF和HIF1a的表达可能有助于更好地了解胰腺癌患者的预后，甚至可能对多模式治疗方案的患者分布起到至关重要的作用。包括接受实际化疗药物治疗的患者在内的更大规模的研究似乎是有必要的。
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.