title: Identification of novel predictive markers for the prognosis of pancreatic ductal adenocarcinoma.
abstract: 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.
authors.affiliation: Experimental Research Center, Laboratory for Pancreatic Diseases, First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Luo
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Qiu
authors.forename: Ling
authors.initials: L
authors.lastname: Tian
authors.forename: Guanghui
authors.initials: G
authors.lastname: Zhu
authors.forename: Ye
authors.initials: Y
authors.lastname: Feng
authors.forename: Miaoying
authors.initials: M
authors.lastname: Yi
authors.forename: Xiafang
authors.initials: X
authors.lastname: Chen
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
authors.forename: Chuanyuan
authors.initials: C
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Huang
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000201:enzymology* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000201:enzymology* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D015415:Biomarkers; D053148:Caspase 3