Identification of novel predictive markers for the prognosis of pancreatic ductal adenocarcinoma.

Pancreatic cancer is a disease with poor prognosis and high mortality. To identify novel molecular markers that could predict the prognosis of pancreatic ductal adenocarcinoma, a total of 114 pancreatic ductal adenocarcinomas and 99 peritumoral tissues were collected. Protein levels of cleaved caspase-3, cyclin D1, epidermal growth factor receptor and Her-2 (human epidermal growth factor receptor 2) were measured by immunohistochemistry. Molecular abnormalities of cyclin D1/q11, Her-2/q17, and epidermal growth factor receptor/p7 were detected using fluorescence in situ hybridization. Results demonstrated that the protein levels of cleaved caspase-3, epidermal growth factor receptor, Her-2, and cyclin D1 were significantly higher in pancreatic ductal adenocarcinoma than that in peritumoral tissues (P = .000). Significantly more amplifications of epidermal growth factor receptor, Her-2, and cyclin D1 were observed in pancreatic ductal adenocarcinoma patients than in peritumoral tissues. In addition, 51.8% of pancreatic ductal adenocarcinoma tumors showed polysomy 7, 50% showed polysomy 11, and 40.4% showed polysomy 17. However, no polysomy was observed in peritumoral tissues. Her-2 amplification and polysomy 17 significantly correlated with poor prognosis of pancreatic ductal adenocarcinoma (P = .008 and P = .005, respectively). Interestingly, only cleaved caspase-3 protein level significantly correlated with poor survival in pancreatic ductal adenocarcinoma patients (P = .000). We also observed significant correlations of cleaved caspase-3 level with epidermal growth factor receptor, Her-2, and cyclin D1 protein levels and the molecular abnormalities of Her-2 and cyclin D1. Conclusively, cleaved caspase-3 level is an ideal biomarker to predict prognosis in pancreatic ductal adenocarcinoma patients and might be a better target for pancreatic ductal adenocarcinoma treatment than epidermal growth factor receptor/Her-2 and cyclin D1.

Duke Scholars

Author Chuan-Yuan Li Dermatology