ABSTRACT
BACKGROUND: Cholangiocarcinoma (CC) is a fatal malignancy, the incidence of which is increasing worldwide, with substantial regional variation. Current diagnostic techniques to distinguish benign from malignant biliary disease are unsatisfactory. Metabolic profiling of bile may help to differentiate benign from malignant disease. No previous studies have compared the metabolic profiles of bile from two geographically and racially distinct groups of CC patients. OBJECTIVES: This study aimed to compare metabolic profiles of bile, using in vitro proton magnetic resonance spectroscopy, from CC patients from Egypt and the UK, and from patients with CC and patients with non-malignant biliary disease. METHODS: A total of 29 bile samples, collected at cholangiography, were analysed using an 11.7-T system. Samples were from eight CC patients in either Egypt (n = 4) or the UK (n = 4) and 21 patients with benign biliary disease (choledocholithiasis [n = 8], sphincter of Oddi dysfunction [n = 8], primary sclerosing cholangitis [n = 5]). RESULTS: Bile phosphatidylcholine (PtC) was significantly reduced in CC patients. Egyptian CC patients had significantly lower biliary PtC levels compared with UK patients. Taurine- and glycine-conjugated bile acids (H-26 and H-25 protons, respectively) were significantly elevated in bile from patients with CC compared with bile from patients with benign diseases (P = 0.013 and P < 0.01, respectively). CONCLUSIONS: Biliary PtC levels potentially differentiate CC from benign biliary disease. Reduced biliary PtC in Egyptian compared with UK patients may reflect underlying carcinogenic mechanisms.
Subject(s)
Bile Acids and Salts/metabolism , Bile Duct Neoplasms/metabolism , Bile Ducts, Intrahepatic/metabolism , Bile/metabolism , Biomarkers, Tumor/metabolism , Cholangiocarcinoma/metabolism , Phosphatidylcholines/metabolism , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/diagnostic imaging , Bile Ducts, Intrahepatic/diagnostic imaging , Cholangiocarcinoma/diagnostic imaging , Cholangiopancreatography, Endoscopic Retrograde , Cholangitis, Sclerosing/metabolism , Choledocholithiasis/metabolism , Diagnosis, Differential , Egypt , Female , Humans , Magnetic Resonance Spectroscopy , Male , Metabolomics/methods , Middle Aged , Predictive Value of Tests , Sphincter of Oddi Dysfunction/metabolism , United KingdomABSTRACT
OBJECTIVES: 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.
