Endoskopie heute 2011; 24 - FV15
DOI: 10.1055/s-0030-1271263

Bile proteomic profiles differentiates cholangiocarcinoma from primary sclerosing cholangitis and choledocholithiasis

T Lankisch 1, J Metzger 2, A Negm 1, K Voßkuhl 1, E Schiffer 2, J Siwy 2, T Weismüller 1, A Schneider 1, K Thedieck 3, R Baumeister 3, P Zürbig 2, M Manns 1, H Mischak 2, J Wedemeyer 1
  • 1Medizinische Hochschule Hannover, Gastroenterologie, Hepatologie und Endokrinologie, Hannover, Germany
  • 2Mosaiques Diagnostics, Hannover, Germany
  • 3Albert-Ludwigs-Universitaet Freiburg, Bioinformatics and Molecular Genetics (Faculty of Biology), Freiburg, Germany

Introduction: Early detection of malignant biliary tract diseases, especially cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis (PSC), is very difficult and often comes too late to give the patient a therapeutic benefit. Endoscopic diagnostic procedures are performed in clinical routine, but imaging methods, biopsies or brush cytology results are not sensitive enough to diagnose CC. Bile analysis obtained during endoscopic procedures as a diagnostic tool has not been studied so far. We hypothesize that bile proteomic analysis distinguishes CC from non-malignant lesions.

Methods: We used capillary electrophoresis mass spectrometry (CE-MS) to identify disease specific peptide patterns in patients with choledocholithiasis (n=16), PSC (n=18) and CC (n=16) in a training set. A model for differentiation of choledocholithiasis from PSC and CC (PSC/CC model) and another model distinguishing CC from PSC (CC model) were subsequently validated in independent cohorts (choledocholithiasis (n=14), PSC (n=18) and CC (n=25)). Peptides were characterized by sequencing.

Results: Application of the PSC/CC model in the independent test cohort resulted in correct exclusion of 12/14 patients with choledocholithiasis and identification of 40/43 patients with PSC or CC (93% sensitivity, 86% specificity). The corresponding receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.93 (95% CI: 0.82–0.98, p=0.0001). The CC model succeeded in an accurate detection of 14/18 patients with PSC and 21/25 patients with CC (84% sensitivity, 78% specificity) in the independent cohort resulting in an AUC-value of 0.87 (95% CI: 0.73–0.95, p=0.0001) in ROC analysis. Eight out of ten patients with CC complicating PSC were identified.

Conclusion: Bile proteomic analysis discriminates benign conditions from CC accurately. This method may become a diagnostic tool in future as it offers a new possibility to diagnose malignant bile duct disease and thus enables efficient therapy particularly in patients with PSC.