High performance diagnostic protein signatures for biliary tract cancer


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.


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.



Christensen T, Maag E, Larsen O, et al. Development and validation of circulating protein signatures as diagnostic biomarkers for biliary tract cancer. (2022) JHEP Reports, DOI 10.1016/j.jhepr.2022.100648

The study also validated the use of multiprotein diagnostic cancer biomarkers based on proximity extension assay technology

Christensen et al. (2022)

Peer-reviewed publications citing the use of Olink panels

Olink’s Proximity Extension Assay (PEA) technology has been used for protein biomarker discovery and analysis across a very broad range of disease areas and applications, providing actionable insights into disease biology and helping to drive future development of new and better therapeutics. There are now well over 1000 publications citing the use of our assays and the list is growing rapidly. Please visit our library of publications to see some of the extraordinary work produced by Olink customers.