Bile proteomic profiles differentiates cholangiocarcinoma from primary sclerosing cholangitis and choledocholithiasis

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. 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=8), PSC (n=9) and CC (n=13)). Peptides were characterized by sequencing. Results: Application of the PSC/CC model in the independent test cohort resulted in correct exclusion of 7/8 patients with choledocholithiasis and identification of 20/22 patients with PSC or CC (88% specificity, 91% sensitivity). The corresponding receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.90 (95% CI: 0.73–0.98, p=0.0001). The CC model succeeded in an accurate detection of 7/9 patients with PSC and 12/13 patients with CC (78% specificity, 92% sensitivity) in the independent cohort resulting in an AUC-value of 0.90 (95% CI: 0.69–0.98, p=0.0001) in ROC analysis. Three out of four 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.

Cholangiocarcinoma - PSC - Proteomic analysis - Tumour marker - bile