Profiling, Identification, And Functional Genomic Study On Molecular Signatures Of Pancreatic Ductal Adenocarcinoma

Pancreatic cancer is a virulent disease with a poor prognosis since the asymptomatic nature of the disease in early stage and lack of effective diagnostic markers. Discovering dysregulated proteins during the development and progression of pancreatic cancer is a key approach to solve the problem. In this study, we used monoclonal antibody microarray, which harbored 378 antibodies targeted the well-known cellular proteins, to profile the differentially expressed proteins between pancreatic cancer and normal pancreatic tissues. It was found 20 differentially expressed proteins between pancreatic ductal adenocarcinoma and normal pancreas containing 11 up-regulated and 9 down-regulated proteins in pancreatic cancer. The antibody microarray is an important and effective tool for comparative proteomic analysis.The expression of gelsolin, one of down-regulated proteins in pancreatic ductal adenocarcinoma, was further verified by Western blot and immunohistochemistry. Gelsolin was significantly reduced or absent in pancreatic ductal adenocarcinoma by Western blot analysis (73%, 8/11). Immunohistochemical staining on pancreatic cancer multi-tissues microarray (MTAs) showed that gelsolin was normally expressed in normal pancreas tissue (71%, 27/38) and obviously reduced in pancreatic cancer (29%, 12/42) (P<0.0001), Additional clinicopathologic analysis found that the positive expression rate of gelsolin in pancreatic cancer without lymph nodes metastasis (20%, 7/35) reduced markedly compared with lymph nodes metastasis (71.4%, 5/7) (P=0.013). Gelsolin was definitely reduced only in the early stages, stage I 20% (3/15) and II 21.1% (4/19). However, following the progress of the tumorigenesis, the expression of gelsolin was increased late in stage III and IV of the pancreatic cancer (62.5%, 5/8) (P=0.022). Gelsolin expression was found with significant correlation with TNM stages.