title: Quantitative proteomics analysis reveals that proteins differentially expressed in chronic pancreatitis are also frequently involved in pancreatic cancer.
abstract: The effective treatment of pancreatic cancer relies on the diagnosis of the disease at an early stage, a difficult challenge. One major obstacle in the development of diagnostic biomarkers of early pancreatic cancer has been the dual expression of potential biomarkers in both chronic pancreatitis and cancer. To better understand the limitations of potential protein biomarkers, we used ICAT technology and tandem mass spectrometry-based proteomics to systematically study protein expression in chronic pancreatitis. Among the 116 differentially expressed proteins identified in chronic pancreatitis, most biological processes were responses to wounding and inflammation, a finding consistent with the underlining inflammation and tissue repair associated with chronic pancreatitis. Furthermore 40% of the differentially expressed proteins identified in chronic pancreatitis have been implicated previously in pancreatic cancer, suggesting some commonality in protein expression between these two diseases. Biological network analysis further identified c-MYC as a common prominent regulatory protein in pancreatic cancer and chronic pancreatitis. Lastly five proteins were selected for validation by Western blot and immunohistochemistry. Annexin A2 and insulin-like growth factor-binding protein 2 were overexpressed in cancer but not in chronic pancreatitis, making them promising biomarker candidates for pancreatic cancer. In addition, our study validated that cathepsin D, integrin beta1, and plasminogen were overexpressed in both pancreatic cancer and chronic pancreatitis. The positive involvement of these proteins in chronic pancreatitis and pancreatic cancer will potentially lower the specificity of these proteins as biomarker candidates for pancreatic cancer. Altogether our study provides some insights into the molecular events in chronic pancreatitis that may lead to diverse strategies for diagnosis and treatment of these diseases.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington 98195, USA. ruc@medicine.washington.edu
authors.forename: Ru
authors.initials: R
authors.lastname: Chen
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Brentnall
authors.forename: Sheng
authors.initials: S
authors.lastname: Pan
authors.forename: Kelly
authors.initials: K
authors.lastname: Cooke
authors.forename: Kara White
authors.initials: KW
authors.lastname: Moyes
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Lane
authors.forename: David A
authors.initials: DA
authors.lastname: Crispin
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.forename: Mary P
authors.initials: MP
authors.lastname: Bronner
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D050500:Pancreatitis, Chronic / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome