title: Bile proteomics for differentiation of malignant from benign biliary strictures: a pilot study.
abstract: BACKGROUND
  Determining the etiology of biliary strictures is challenging, and the sensitivities of the current tests to diagnose them are low. Protein biomarkers in bile, in combination with other tests, may improve sensitivity in diagnosing biliary strictures.
  
  
  OBJECTIVE
  To analyse the differential abundance of proteins in benign and malignant biliary strictures through proteomic analysis of bile.
  
  
  METHODS
  In this prospective, cross-sectional study, bile was aspirated in 24 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) including six patients with primary sclerosing cholangitis (PSC), three with cholangiocarcinoma (CCA), ten with pancreatic cancer, and five with benign biliary conditions. Liquid chromatography/mass spectrometry was used to examine the bile for differential abundance of protein biomarkers. The relative abundance of various proteins was compared in the malignant vs. benign groups and in CCA vs. PSC.
  
  
  RESULTS
  The majority of the proteins identified in bile were similar to those of the plasma (plasma proteins) and certain proteins were differentially expressed among the different groups (CCA, pancreatic cancer, PSC or benign). A total of 18 proteins were identified as being more abundant in the malignant group (CCA and pancreatic cancer) than in the benign strictures group, including myeloperoxidase, complement C3, inter-alpha-trypsin inhibitor heavy chain H4, apolipoprotein B-100, and kininogen-1 isoform 2. A total of 30 proteins were identified to be less abundant in the malignant group than in the benign group, including trefoil factor 2, superoxide dismutase [Cu-Zn], kallikrein-1, carboxypeptidase B and trefoil factor 1.
  
  
  CONCLUSIONS
  Protein biomarkers in bile may differentiate malignant from benign biliary strictures. Larger studies are warranted to validate these observations.
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA and Proteomics Core Laboratory, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA udhaykumar81@gmail.com.
authors.forename: Udayakumar
authors.initials: U
authors.lastname: Navaneethan
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA and Proteomics Core Laboratory, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Vennisvasanth
authors.initials: V
authors.lastname: Lourdusamy
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA and Proteomics Core Laboratory, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Preethi
authors.initials: P
authors.lastname: Gk Venkatesh
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA and Proteomics Core Laboratory, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Belinda
authors.initials: B
authors.lastname: Willard
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA and Proteomics Core Laboratory, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Madhusudhan R
authors.initials: MR
authors.lastname: Sanaka
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA and Proteomics Core Laboratory, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Mansour A
authors.initials: MA
authors.lastname: Parsi
keywords: bile; cholangiocarcinoma; pancreatic cancer; proteomics