Circulating Protein Biomarkers for Prognostic Use in Patients with Advanced Pancreatic Ductal Adenocarcinoma Undergoing Chemotherapy

Sidsel C. Lindgaard*, Emil Maag, Zsófia Sztupinszki, Inna M. Chen, Astrid Z. Johansen, Benny V. Jensen, Stig E. Bojesen, Dorte L. Nielsen, Zoltan Szallasi, Julia S. Johansen

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Abstract

Patients with advanced pancreatic ductal adenocarcinoma (PDAC) have a dismal prognosis. We aimed to find a prognostic protein signature for overall survival (OS) in patients with advanced PDAC, and to explore whether early changes in circulating-protein levels could predict survival. We investigated 92 proteins using the Olink Immuno-Oncology panel in serum samples from 363 patients with advanced PDAC. Protein panels for several survival cut-offs were developed independently by two bioinformaticians using LASSO and Ridge regression models. Two panels of proteins discriminated patients with OS < 90 days from those with OS > 2 years. Index I (CSF-1, IL-6, PDCD1, TNFRSF12A, TRAIL, TWEAK, and CA19-9) had AUCs of 0.99 (95% CI: 0.98–1) (discovery cohort) and 0.89 (0.74–1) (replication cohort). For Index II (CXCL13, IL-6, PDCD1, and TNFRSF12A), the corresponding AUCs were 0.97 (0.93–1) and 0.82 (0.68–0.96). Four proteins (ANGPT2, IL-6, IL10, and TNFRSF12A) were associated with survival across all treatment groups. Longitudinal samples revealed several changes, including four proteins that were also part of the prognostic signatures (CSF-1, CXCL13, IL-6, TNFRSF12A). This study identified two circulating-protein indices with the potential to identify patients with advanced PDAC with very short OS and with long OS.

OriginalsprogEngelsk
Artikelnummer3250
TidsskriftCancers
Vol/bind14
Udgave nummer13
ISSN2072-6694
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Funding: This research was funded by Celgene (GRANT-DNK-130), the VELUX Foundation (NA), The Danish Cancer Society (A13157, KC2018), the Harboe Foundation (19003), the Beckett Foundation (19-2-3424), the Foundation of Merchant M. Kristjan Kjær and wife Margrethe Kjær (41447-001), and the Memorial Fund of Carpenter Holm (20006-1926).

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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