Kristiansen Glen, Jacob Juliane, Buckendahl Ann-Christin, Grützmann Robert, Alldinger Ingo, Sipos Bence, Klöppel Günter, Bahra Marcus, Langrehr Jan M, Neuhaus Peter, Dietel Manfred, Pilarsky Christian
Institute of Pathology and Department of Surgery, Charité University Hospital, Berlin, Germany.
Clin Cancer Res. 2006 Nov 1;12(21):6444-51. doi: 10.1158/1078-0432.CCR-06-0834.
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor that has been implicated in carcinogenesis and progression of various solid tumors, including pancreatic carcinoma. We aimed to clarify the expression patterns of PPARgamma in pancreatic ductal carcinomas and to correlate these to clinicopathologic variables, including patient survival.
Array-based expression profiling of 19 microdissected carcinomas and 14 normal ductal epithelia was conducted. Additionally, Western blots of pancreatic cancer cell lines and paraffinized tissue of 129 pancreatic carcinomas were immunostained for PPARgamma. For statistical analysis, Fisher's exact test, chi2 test for trends, correlation analysis, Kaplan-Meier analysis, and Cox's regression were applied.
Expression profiles showed a strong overexpression of PPARgamma mRNA (change fold, 6.9; P=0.04). Immunohistochemically, PPARgamma expression was seen in 71.3% of pancreatic cancer cases. PPARgamma expression correlated positively to higher pT stages and higher tumor grade. Survival analysis showed a significant prognostic value for PPARgamma, which was found to be independent in the clinically important subgroup of node-negative tumors.
PPARgamma is commonly up-regulated in pancreatic ductal adenocarcinoma and might be a prognostic marker in this disease. Both findings corroborate the importance of PPARgamma in tumor progression of pancreatic cancer.
过氧化物酶体增殖物激活受体γ（PPARγ）是一种配体激活的转录因子，已被证实与包括胰腺癌在内的多种实体肿瘤的发生和进展有关。我们旨在阐明PPARγ在胰腺导管癌中的表达模式，并将其与包括患者生存率在内的临床病理变量相关联。
对19例显微切割癌和14例正常导管上皮进行基于芯片的表达谱分析。此外，对胰腺癌细胞系和129例胰腺癌石蜡组织进行Western印迹，以检测PPARγ的免疫染色情况。采用Fisher精确检验、趋势χ2检验、相关性分析、Kaplan-Meier分析和Cox回归进行统计学分析。
表达谱显示PPARγ mRNA有强烈的过表达（变化倍数为6.9；P = 0.04）。免疫组织化学显示，71.3%的胰腺癌病例中有PPARγ表达。PPARγ表达与较高的pT分期和较高的肿瘤分级呈正相关。生存分析显示PPARγ具有显著的预后价值，在淋巴结阴性肿瘤这一重要临床亚组中发现其具有独立性。
PPARγ在胰腺导管腺癌中普遍上调，可能是该疾病的一个预后标志物。这两个发现都证实了PPARγ在胰腺癌肿瘤进展中的重要性。
