title: Protein alterations associated with pancreatic cancer and chronic pancreatitis found in human plasma using global quantitative proteomics profiling.
abstract: Pancreatic cancer is a lethal disease that is difficult to diagnose at early stages when curable treatments are effective. Biomarkers that can improve current pancreatic cancer detection would have great value in improving patient management and survival rate. A large scale quantitative proteomics study was performed to search for the plasma protein alterations associated with pancreatic cancer. The enormous complexity of the plasma proteome and the vast dynamic range of protein concentration therein present major challenges for quantitative global profiling of plasma. To address these challenges, multidimensional fractionation at both protein and peptide levels was applied to enhance the depth of proteomics analysis. Employing stringent criteria, more than 1300 proteins total were identified in plasma across 8-orders of magnitude in protein concentration. Differential proteins associated with pancreatic cancer were identified, and their relationship with the proteome of pancreatic tissue and pancreatic juice from our previous studies was discussed. A subgroup of differentially expressed proteins was selected for biomarker testing using an independent cohort of plasma and serum samples from well-diagnosed patients with pancreatic cancer, chronic pancreatitis, and nonpancreatic disease controls. Using ELISA methodology, the performance of each of these protein candidates was benchmarked against CA19-9, the current gold standard for a pancreatic cancer blood test. A composite marker of TIMP1 and ICAM1 demonstrate significantly better performance than CA19-9 in distinguishing pancreatic cancer from the nonpancreatic disease controls and chronic pancreatitis controls. In addition, protein AZGP1 was identified as a biomarker candidate for chronic pancreatitis. The discovery and technical challenges associated with plasma-based quantitative proteomics are discussed and may benefit the development of plasma proteomics technology in general. The protein candidates identified in this study provide a biomarker candidate pool for future investigations.
authors: Department of Medicine, University of Washington, Seattle, Washington 98195, United States.
authors: Sheng
authors: S
authors: Pan
authors: Ru
authors: R
authors: Chen
authors: David A
authors: DA
authors: Crispin
authors: Damon
authors: D
authors: May
authors: Tyler
authors: T
authors: Stevens
authors: Martin W
authors: MW
authors: McIntosh
authors: Mary P
authors: MP
authors: Bronner
authors: Argyrios
authors: A
authors: Ziogas
authors: Hoda
authors: H
authors: Anton-Culver
authors: Teresa A
authors: TA
authors: Brentnall
mesh_terms: D054392:Adipokines; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis*; D002352:Carrier Proteins / Q000097:blood; D002853:Chromatography, Liquid; D019295:Computational Biology; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D010190:Pancreatic Neoplasms / Q000097:blood*; D050500:Pancreatitis, Chronic / Q000097:blood*; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D000090203:Zn-Alpha-2-Glycoprotein
chemical_list: D054392:Adipokines; D014408:Biomarkers, Tumor; D001798:Blood Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D018799:Intercellular Adhesion Molecule-1; D019715:Tissue Inhibitor of Metalloproteinase-1; C488891:AZGP1 protein, human; D000090203:Zn-Alpha-2-Glycoprotein