title: Urine proteomic analysis differentiates cholangiocarcinoma from primary sclerosing cholangitis and other benign biliary disorders.
abstract: BACKGROUND
  Diagnosis and curative treatment of cholangiocarcinoma (CC) often comes too late due to the lack of reliable tumour markers especially in patients with primary sclerosing cholangitis (PSC). The authors recently introduced bile proteomic analysis for CC diagnosis. Nevertheless, bile collection depends on invasive endoscopic retrograde cholangiography. The authors therefore evaluated urine proteomic analysis for non-invasive CC diagnosis.
  
  
  METHODS
  Using capillary electrophoresis mass spectrometry the authors established a CC-specific peptide marker model based on the distribution of 42 peptides in 14 CC, 13 PSC and 14 benign biliary disorder (BBD) patients.
  
  
  RESULTS
  In cross-sectional validation of 123 patients, the urine peptide marker model correctly classified 35 of 42 CC patients and 64 of 81 PSC and BBD patients with an area under the curve value of 0.87 (95% CI 0.80 to 0.92, p=0.0001, 83% sensitivity, 79% specificity). Evaluation of 101 normal controls resulted in 86% specificity. All 10 patients with CC on top of PSC were correctly classified. The majority of sequence-identified peptides are fragments of interstitial collagens with some of them also detected in blood indicating their extra-renal origin. Immunostaining of liver sections for matrix metallopeptidase 1 indicated increased activity of the interstitial collagenase in liver epithelial cells of CC patients.
  
  
  CONCLUSIONS
  The urine test differentiates CC from PSC and other BBD and may provide a new diagnostic non-invasive tool for PSC surveillance and CC detection.
authors.affiliation: Mosaiques diagnostics GmbH, Hannover, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Metzger
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Negm
authors.forename: Ruben R
authors.initials: RR
authors.lastname: Plentz
authors.forename: Tobias J
authors.initials: TJ
authors.lastname: Weismüller
authors.forename: Jochen
authors.initials: J
authors.lastname: Wedemeyer
authors.forename: Tom H
authors.initials: TH
authors.lastname: Karlsen
authors.forename: Mohammed
authors.initials: M
authors.lastname: Dakna
authors.forename: William
authors.initials: W
authors.lastname: Mullen
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Tim O
authors.initials: TO
authors.lastname: Lankisch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000652:urine; D001653:Bile Ducts, Intrahepatic; D015415:Biomarkers / Q000652:urine*; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000652:urine; D015209:Cholangitis, Sclerosing / Q000175:diagnosis* / Q000652:urine; D016000:Cluster Analysis; D003430:Cross-Sectional Studies; D003937:Diagnosis, Differential; D019075:Electrophoresis, Capillary; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010449:Peptide Mapping; D040901:Proteomics; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers