title: Proteins associated with disease and clinical course in pancreas cancer: a proteomic analysis of plasma in surgical patients.
abstract: New biomarkers for pancreas cancer are needed to improve its detection and management. We surveyed the plasma of patients undergoing surgical resection to identify proteins which change in abundance after complete resection of tumor. Using longitudinally collected specimens from surgical patients, we control for normal inter-individual variation which can confound cross-sectional analysis. Recent refinements in two-dimensional gel electrophoresis allowed us to quantify changes in low abundance plasma proteins with precision. To circumvent the traditional limitations of image analysis in comparing two-dimensional gels, we used fluorometric two-dimensional difference gel electrophoresis to resolve the proteins from pre- and post-surgical plasma from each patient on one physical gel. Furthermore, we increased the ability of our assay to detect low-abundance proteins by depleting the plasma of 12 high-abundance proteins with a multi-affinity column. Informative protein spots from 20 plasma samples across 10 patients were submitted for identification with mass-spectrometry. We identified a group of proteins which change consistently in plasma following complete resection of pancreas tumor. Furthermore, we identified proteins which correlate with post-surgical rapid recurrence of disease. With further identification and validation, the candidate biomarkers which we identify in this study may prove to be useful in the diagnosis, management and prognostication of patients with pancreas cancer.
authors.affiliation: Departments of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Yiing
authors.initials: Y
authors.lastname: Lin
authors.forename: Peter S
authors.initials: PS
authors.lastname: Goedegebuure
authors.forename: Marcus C B
authors.initials: MC
authors.lastname: Tan
authors.forename: Julia
authors.initials: J
authors.lastname: Gross
authors.forename: James P
authors.initials: JP
authors.lastname: Malone
authors.forename: Sheng
authors.initials: S
authors.lastname: Feng
authors.forename: Justin
authors.initials: J
authors.lastname: Larson
authors.forename: Chanpheng
authors.initials: C
authors.lastname: Phommaly
authors.forename: Kathryn
authors.initials: K
authors.lastname: Trinkaus
authors.forename: R Reid
authors.initials: RR
authors.lastname: Townsend
authors.forename: David C
authors.initials: DC
authors.lastname: Linehan
mesh_terms: D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D013058:Mass Spectrometry; D008923:Missouri; D009363:Neoplasm Proteins / Q000097:blood* / Q000302:isolation & purification; D010190:Pancreatic Neoplasms / Q000097:blood*; D010949:Plasma / Q000737:chemistry*; D040901:Proteomics / Q000379:methods
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D009363:Neoplasm Proteins