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Title

An integrated approach for comparative proteomic analysis of human bile reveals overexpressed cancer-associated proteins in malignant biliary stenosis

Authors
Delhaye, Myriam
Published in Biochimica et Biophysica Acta. 2014, vol. 1844, no. 5, p. 1026-33
Abstract Proteomics is a key tool in the identification of new bile biomarkers for differentiating malignant and nonmalignant biliary stenoses. Unfortunately, the complexity of bile and the presence of molecules interfering with protein analysis represent an obstacle for quantitative proteomic studies in bile samples. The simultaneous need to introduce purification steps and minimize the use of pre-fractionation methods inevitably leads to protein loss and limited quantifications. This dramatically reduces the chance of identifying new potential biomarkers. In the present study, we included differential centrifugation as a preliminary step in a quantitative proteomic workflow involving iTRAQ labeling, peptide fractionation by OFFGEL electrophoresis and LC-MS/MS, to compare protein expression in bile samples collected from patients with malignant or nonmalignant biliary stenoses. A total of 1267 proteins were identified, including a set of 322 newly described bile proteins, mainly belonging to high-density cellular fractions. The subsequent comparative analysis led to a 5-fold increase in the number of quantified proteins over previously published studies and highlighted 104 proteins overexpressed in malignant samples. Finally, immunoblot verifications performed on a cohort of 8 malignant (pancreatic adenocarcinoma, n=4; cholangiocarcinoma, n=4) and 5 nonmalignant samples (chronic pancreatitis, n=3; biliary stones, n=2) confirmed the results of proteomic analysis for three proteins: olfactomedin-4, syntenin-2 and Ras-related C3 botulinum toxin substrate 1. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.
Keywords Adenocarcinoma/complications/metabolismAgedAged, 80 and overBile Duct Neoplasms/complications/metabolismBile Ducts, Intrahepatic/metabolism/pathologyCholangiocarcinoma/complications/metabolismCholestasis/diagnosis/etiology/metabolismChromatography, LiquidCohort StudiesFemaleHumansImmunoblottingMaleMiddle AgedPancreatic Neoplasms/complications/metabolismPancreatitis, Chronic/complications/metabolismProteomics/methodsTandem Mass SpectrometryTumor Markers, Biological/metabolism
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PMID: 23872482
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Research group Chimie et protéomique clinique (270)
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LUKIC, Natalija et al. An integrated approach for comparative proteomic analysis of human bile reveals overexpressed cancer-associated proteins in malignant biliary stenosis. In: Biochimica et Biophysica Acta, 2014, vol. 1844, n° 5, p. 1026-33. https://archive-ouverte.unige.ch/unige:41739

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Deposited on : 2014-11-12

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