Circulating Protein Biomarkers for Prognostic Use in Patients with Advanced Pancreatic Ductal Adenocarcinoma Undergoing Chemotherapy
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Circulating Protein Biomarkers for Prognostic Use in Patients with Advanced Pancreatic Ductal Adenocarcinoma Undergoing Chemotherapy. / Lindgaard, Sidsel C.; Maag, Emil; Sztupinszki, Zsófia; Chen, Inna M.; Johansen, Astrid Z.; Jensen, Benny V.; Bojesen, Stig E.; Nielsen, Dorte L.; Szallasi, Zoltan; Johansen, Julia S.
I: Cancers, Bind 14, Nr. 13, 3250, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Circulating Protein Biomarkers for Prognostic Use in Patients with Advanced Pancreatic Ductal Adenocarcinoma Undergoing Chemotherapy
AU - Lindgaard, Sidsel C.
AU - Maag, Emil
AU - Sztupinszki, Zsófia
AU - Chen, Inna M.
AU - Johansen, Astrid Z.
AU - Jensen, Benny V.
AU - Bojesen, Stig E.
AU - Nielsen, Dorte L.
AU - Szallasi, Zoltan
AU - Johansen, Julia S.
N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - biomarkers
KW - inflammation
KW - pancreatic cancer
KW - prognosis
KW - protein arrays
U2 - 10.3390/cancers14133250
DO - 10.3390/cancers14133250
M3 - Journal article
C2 - 35805022
AN - SCOPUS:85133125410
VL - 14
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 13
M1 - 3250
ER -
ID: 321973172