title: Proteomics portrait of archival lesions of chronic pancreatitis.
abstract: Chronic pancreatitis is a chronic inflammatory disorder of the pancreas. The etiology is multi-fold, but all lead to progressive scarring and loss of pancreatic function. Early diagnosis is difficult; and the understanding of the molecular events that underlie this progressive disease is limited. In this study, we investigated differential proteins associated with mild and severe chronic pancreatitis in comparison with normal pancreas and pancreatic cancer. Paraffin-embedded formalin-fixed tissues from five well-characterized specimens each of normal pancreas (NL), mild chronic pancreatitis (MCP), severe chronic pancreatitis (SCP) and pancreatic ductal adenocarcinoma (PDAC) were subjected to proteomic analysis using a "label-free" comparative approach. Our results show that the numbers of differential proteins increase substantially with the disease severity, from mild to severe chronic pancreatitis, while the number of dysregulated proteins is highest in pancreatic adenocarcinoma. Important functional groups and biological processes associated with chronic pancreatitis and cancer include acinar cell secretory proteins, pancreatic fibrosis/stellate cell activation, glycoproteins, and inflammatory proteins. Three differential proteins were selected for verification by immunohistochemistry, including collagen 14A1, lumican and versican. Further canonical pathway analysis revealed that acute phase response signal, prothrombin activation pathway, and pancreatic fibrosis/pancreatic stellate cell activation pathway were the most significant pathways involved in chronic pancreatitis, while pathways relating to metabolism were the most significant pathways in pancreatic adenocarcinoma. Our study reveals a group of differentially expressed proteins and the related pathways that may shed light on the pathogenesis of chronic pancreatitis and the common molecular events associated with chronic pancreatitis and pancreatic adenocarcinoma.
authors: Department of Medicine, University of Washington, Seattle, Washington, United States of America. shengp@medicine.washington.edu
authors: Sheng
authors: S
authors: Pan
authors: Ru
authors: R
authors: Chen
authors: Tyler
authors: T
authors: Stevens
authors: Mary P
authors: MP
authors: Bronner
authors: Damon
authors: D
authors: May
authors: Yasuko
authors: Y
authors: Tamura
authors: Martin W
authors: MW
authors: McIntosh
authors: Teresa A
authors: TA
authors: Brentnall
mesh_terms: D061354:Acinar Cells / Q000378:metabolism / Q000473:pathology; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D018070:Biological Specimen Banks; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D016000:Cluster Analysis; D003094:Collagen / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007632:Keratan Sulfate / Q000378:metabolism; D000071234:Lumican; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D058954:Pancreatic Stellate Cells / Q000378:metabolism / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000378:metabolism* / Q000473:pathology*; D011506:Proteins / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D015398:Signal Transduction; D013194:Staining and Labeling; D053675:Versicans / Q000378:metabolism
chemical_list: C054447:COL14A1 protein, human; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C000604306:LUM protein, human; D000071234:Lumican; D011506:Proteins; D053675:Versicans; D003094:Collagen; D007632:Keratan Sulfate