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Molecular & Cellular Proteomics 6:1331-1342, 2007.
© 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

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Research

Quantitative Proteomics Analysis Reveals That Proteins Differentially Expressed in Chronic Pancreatitis Are Also Frequently Involved in Pancreatic Cancer^*,S

Ru Chen^,, Teresa A. Brentnall, Sheng Pan^¶, Kelly Cooke^||, Kara White Moyes, Zhaoli Lane^**, David A. Crispin, David R. Goodlett, Ruedi Aebersold and Mary P. Bronner^**

From the Division of Gastroenterology, Department of Medicine, and Departments of ^¶ Pathology and Medicinal Chemistry, University of Washington, Seattle, Washington 98195, ^|| Institute for Systems Biology, Seattle, Washington 98103, ^** Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio 44195, and Institute of Molecular Systems Biology, Swiss Federal Institute of Technology Zurich and Faculty of Science, University of Zurich, Zurich CH-8093, Switzerland

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 ß1, 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.

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