Background
Biliary tract cancer (BTC) currently has very poor prognosis, largely due to late diagnosis and a lack of good diagnostic biomarkers. The protein CA19-9 is the most widely used biomarker for BTC, but its use is limited by low sensitivity and specificity, particularly in early stage disease. A team from Copenhagen University Hospital used the Olink Target 96 Immuno-oncology panel to look for proteins that could distinguish BTC vs controls using multiple cohorts for discovery and validation.
Outcome
In the discovery cohort, 64 Olink-measured proteins (plus CA19-9) were significantly different in BTC vs controls and eight of these (CA19-9, CCL20, IL-6, IL-8, CAIX, MMP-12, ADGRG1, and IL-10 ) showed a log2 increase of >1. Further analysis of the data enabled them to generate 16 signatures (all including CA19-9 and CCL20) based on between 2-82 proteins, which were examined for their abilities to discriminate BTC from controls by ROC analysis. These showed very high degrees of accuracy in the discovery cohort (AUCs of 0.95 to 0.99) and these maintained performance in the replication and validation cohorts. In general, combining several proteins improved performance compared to single or dual markers, but adding more than 15 proteins to the signatures did not improve the performance significantly. It was also notable that the signatures maintained high performance even when comparing early stage BTC to controls.
