Multi-protein prognostic signatures for biliary tract cancer


A group from Copenhagen University Hospital  has used the Olink® Target 96 Immuno-oncology panel to look at blood biomarkers in four cohorts of patients with biliary tract cancer who had undergone various types of therapy including chemotherapy or surgery. The relative levels of 89 proteins were then compared among groups of patients defined by time-ranges of overall survival (OS) in order to identify potential prognostic markers.


In the discovery cohort, 29 proteins were significantly associated with survival time after multivariate analyses adjusting for CA19-9 (an established clinical marker) and other clinical variables. In the main validation cohort, 6 proteins were significantly associated with poor overall survival in univariate analysis (IL-15, IL-6, MUC-16, PD-L1, HGF, PGF), but only IL-6 & Il-15 retained significance when adjusting for multiple factors such as tumor stage and location. They then looked at multi-protein signatures, which had different performance characteristics depending on the survival periods compared: signatures were comparable with the best individual proteins for <12 months vs >12 months for example, but a combination of IL-6, MUC-16, IL-15, CCL23, MICA/B and PTN achieved a high-performance predictive value when comparing OS periods of <3 months vs >24 months, with an AUC of 0.91 in the replication cohort .



Christensen TD, Madsen K, Maag E, et al. Protein Signatures and Individual Circulating Proteins, including IL-6 and IL-15, Associated with Prognosis in Patients with Biliary Tract Cancer. (2023) Cancers, DOI: 10.3390/cancers15041062

The study identified several circulating proteins as prognostic biomarkers in patients, with BTC, IL-6, and IL-15 being the most promising markers. Combining proteins in a prognostic signature improved prognostic performance, but future studies are needed to determine the optimal combination and thresholds

Christensen et al. (2023)

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