title: Metabolic profiling of bile in cholangiocarcinoma using in vitro magnetic resonance spectroscopy.
abstract: OBJECTIVE
  Cholangiocarcinoma (CCA) has a poor prognosis and its aetiology is inadequately understood. Magnetic resonance spectroscopy (MRS) of bile may provide insights into the pathogenesis of CCA and help identify novel diagnostic biomarkers. The aim of this study was to compare the chemical composition of bile from patients with CCA with that of bile from patients with benign biliary disease.
  
  
  METHODS
  Magnetic resonance spectra were acquired from the bile of five CCA patients and compared with MRS of control bile from patients with benign biliary disease (seven with gallstones, eight with sphincter of Oddi dysfunction [SOD], five with primary sclerosing cholangitis [PSC]). Metabolic profiles were compared using both univariate and multivariate pattern-recognition analysis.
  
  
  RESULTS
  Univariate analysis showed that levels of glycine-conjugated bile acids were significantly increased in patients with CCA, compared with the benign disease groups (P= 0.002). 7 beta primary bile acids were significantly increased (P= 0.030) and biliary phosphatidylcholine (PtC) levels were reduced (P= 0.010) in bile from patients with CCA compared with bile from gallstone patients. These compounds were also of primary importance in the multivariate analysis: the cohorts were differentiated by partial least squares discriminant analysis (PLS-DA).
  
  
  CONCLUSIONS
  These preliminary data suggest that altered bile acid and PtC metabolism play an important role in CCA aetiopathogenesis and that specific metabolites may have potential as future biomarkers.
authors.affiliation: Hepatology and Gastroenterology Section, Department of Medicine, Imperial College London, London, UK. amar.sharif@imperial.ac.uk
authors.forename: Amar W
authors.initials: AW
authors.lastname: Sharif
authors.forename: Horace R T
authors.initials: HR
authors.lastname: Williams
authors.forename: Temi
authors.initials: T
authors.lastname: Lampejo
authors.forename: Shahid A
authors.initials: SA
authors.lastname: Khan
authors.forename: Devinder S
authors.initials: DS
authors.lastname: Bansi
authors.forename: David
authors.initials: D
authors.lastname: Westaby
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Thillainayagam
authors.forename: Howard C
authors.initials: HC
authors.lastname: Thomas
authors.forename: I Jane
authors.initials: IJ
authors.lastname: Cox
authors.forename: Simon D
authors.initials: SD
authors.lastname: Taylor-Robinson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D008131:London; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D015999:Multivariate Analysis; D010363:Pattern Recognition, Automated; D010713:Phosphatidylcholines / Q000378:metabolism; D025341:Principal Component Analysis; D011379:Prognosis
chemical_list: D001647:Bile Acids and Salts; D014408:Biomarkers, Tumor; D010713:Phosphatidylcholines; D005998:Glycine