Urinproteom-Analyse differenziert Cholangiokarzinom von primär sklerosierender Cholangitis und anderen benignen biliären Erkrankungen

Aims: 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). We recently introduced bile proteomic analysis for CC diagnosis. Nevertheless, bile collection depends on invasive endoscopic retrograde cholangiography. We therefore evaluated urine proteomic analysis for non-invasive CC diagnosis.

Methods: Using capillary electrophoresis mass spectrometry we 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% confidence interval: 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 (MMP-1) indicated increased activity of the interstitial collagenase in liver epithelial cells of CC patients.

Conclusion: 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.

Hepatologie: Wohin führt der Weg?
Freitag, 21. September 2012/15:30–17:00/Saal C