Peroxisome proliferator-activated receptor-gamma and retinoid X receptor-alpha expression in pancreatic ductal adenocarcinoma: association with clinicopathological parameters, tumor proliferative capacity, and patients' survival

摘要

Background Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a ligand-activated transcription factor that forms heterodimers with the retinoid X receptors (RXRs), is overexpressed in various tumors, regulating many aspects of cancer biology. The aim of the present study was to evaluate the clinical significance of PPAR-gamma and RXR-alpha expression in pancreatic adenocarcinoma. Material and Method PPAR-gamma and RXR-alpha protein expression was assessed immunohistochemically in tumoral samples of 65 pancreatic adenocarcinoma patients and statistically analyzed in relation to clinicopathological characteristics, tumor proliferative capacity, and patients' survival. Results Of the 65 adenocarcinoma patients, 49 (75%) tested positive for PPAR-gamma and 55 (85%) stained positive for RXR-alpha. RXR-alpha positivity was significantly associated with tumor proliferative capacity and PPAR-gamma positivity (p=0.022 and p=0.043, respectively). PPAR-gamma and RXR-alpha staining intensity were associated with the histopathological tumor grade (p=0.003 and p=0.038, respectively). Significant associations of PPAR-gamma staining intensity and RXR-alpha expression with tumor size were also noted (p=0.041 and p=0.038, respectively). Moderate and intense PPAR-gamma staining intensity was associated with shorter overall survival in univariate analysis (log-rank test, p=0.023) and proved to be an independent prognostic factor in multivariate analysis (p=0.045), whereas RXR-alpha failed to predict patients' survival. Conclusions These data revealed that both PPAR-gamma and RXR-alpha were associated with pancreatic cancer characteristics. PPAR-gamma, but not RXR-alpha, was found to be an independent prognostic indicator. However, further molecular and clinical studies are required to delineate the potential clinical application of PPAR-gamma and RXR-alpha in the prognosis and management of pancreatic adenocarcinoma patients.