Bile proteomic profiles differentiate cholangiocarcinoma from primary sclerosing cholangitis and choledocholithiasis.

Abstract

UNLABELLED:

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. We hypothesize that bile proteomic analysis distinguishes CC from nonmalignant lesions. 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. Application of the PSC/CC model in the independent test cohort resulted in correct exclusion of 12/14 bile samples from patients with choledocholithiasis and identification of 40/43 patients with PSC or CC (86% specificity, 93% sensitivity). The corresponding receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.93 (95% confidence interval [CI]: 0.82-0.98, P = 0.0001). The CC model succeeded in an accurate detection of 14/18 bile samples from patients with PSC and 21/25 samples with CC (78% specificity, 84% sensitivity) 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 10 samples of 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.

• Authors: Tim O Lankisch, Jochen Metzger, Ahmed A Negm, Katja Vosskuhl, Eric Schiffer, Justyna Siwy, Tobias J Weismüller, Andrea S Schneider, Kathrin Thedieck, Ralf Baumeister, Petra Zürbig, Eva M Weissinger, Michael P Manns, Harald Mischak, Jochen Wedemeyer
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 53 Issue 3 Pg. 875-84 (Mar 2011) ISSN: 1527-3350 [Electronic] United States
• PMID: 21374660 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Association for the Study of Liver Diseases.

Chemical References

• Proteome

Topics

• Adult
• Aged
• Aged, 80 and over
• Bile (chemistry)
• Cholangiocarcinoma (diagnosis)
• Cholangitis, Sclerosing (diagnosis)
• Choledocholithiasis (diagnosis)
• Electrophoresis, Capillary
• Female
• Gene Expression Profiling
• Humans
• Male
• Mass Spectrometry
• Middle Aged
• Proteome (analysis)