Circulating protein biomarkers for use in pancreatic ductal adenocarcinoma identification
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Circulating protein biomarkers for use in pancreatic ductal adenocarcinoma identification. / Lindgaard, Sidsel C.; Sztupinszki, Zsófia; Maag, Emil; Chen, Inna M.; Johansen, Astrid Z.; Jensen, Benny V.; Bojesen, Stig E.; Nielsen, Dorte L.; Hansen, Carsten P.; Hasselby, Jane P.; Nielsen, Kaspar R.; Szallasi, Zoltan; Johansen, Julia S.
In: Clinical Cancer Research, Vol. 27, No. 9, 2021, p. 2592-2603.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Circulating protein biomarkers for use in pancreatic ductal adenocarcinoma identification
AU - Lindgaard, Sidsel C.
AU - Sztupinszki, Zsófia
AU - Maag, Emil
AU - Chen, Inna M.
AU - Johansen, Astrid Z.
AU - Jensen, Benny V.
AU - Bojesen, Stig E.
AU - Nielsen, Dorte L.
AU - Hansen, Carsten P.
AU - Hasselby, Jane P.
AU - Nielsen, Kaspar R.
AU - Szallasi, Zoltan
AU - Johansen, Julia S.
N1 - Publisher Copyright: © 2021 American Association for Cancer Research.
PY - 2021
Y1 - 2021
N2 - Purpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid tumors. Most patients are diagnosed at an advanced stage where curative surgery is not an option. The aim of this study was to identify a panel of circulating proteins that could distinguish patients with PDAC from non-PDAC individuals. Experimental Design: We investigated 92 proteins known to be involved in inflammation, development, and progression of PDAC using the Olink immuno-oncology panel in serum samples from 701 patients with PDAC (stage I-IV), 102 patients with nonmalignant pancreatic diseases, and 180 healthy blood donors. Patients were included prospectively between 2008 and 2018. Plasma carbohydrate antigen 19-9 (CA19-9) was measured in all samples. The protein panels with the best diagnostic performances were developed by two bioinformaticians working independently, using LASSO and Ridge regression models. Results: Two panels of proteins (index I, containing 9 proteins+ CA19-9, and index II, containing 23 proteins + CA19-9) were identified. Index I was able to discriminate patients with PDAC from all patients with non-PDAC, with a ROC AUC value of 0.92 [95% confidence interval (CI), 0.89-0.96] in the discovery cohort and 0.92 (95% CI, 0.87-0.97) in the replication cohort. For index II, the AUC value was 0.96 (95% CI, 0.95-0.98) in the discovery cohort and 0.93 (95% CI, 0.90-0.96) in the replication cohort. All nine serum proteins of index I were found in index II. Conclusions: This study identified two circulating protein indices with the potential to discriminate between individuals with and without PDAC.
AB - Purpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid tumors. Most patients are diagnosed at an advanced stage where curative surgery is not an option. The aim of this study was to identify a panel of circulating proteins that could distinguish patients with PDAC from non-PDAC individuals. Experimental Design: We investigated 92 proteins known to be involved in inflammation, development, and progression of PDAC using the Olink immuno-oncology panel in serum samples from 701 patients with PDAC (stage I-IV), 102 patients with nonmalignant pancreatic diseases, and 180 healthy blood donors. Patients were included prospectively between 2008 and 2018. Plasma carbohydrate antigen 19-9 (CA19-9) was measured in all samples. The protein panels with the best diagnostic performances were developed by two bioinformaticians working independently, using LASSO and Ridge regression models. Results: Two panels of proteins (index I, containing 9 proteins+ CA19-9, and index II, containing 23 proteins + CA19-9) were identified. Index I was able to discriminate patients with PDAC from all patients with non-PDAC, with a ROC AUC value of 0.92 [95% confidence interval (CI), 0.89-0.96] in the discovery cohort and 0.92 (95% CI, 0.87-0.97) in the replication cohort. For index II, the AUC value was 0.96 (95% CI, 0.95-0.98) in the discovery cohort and 0.93 (95% CI, 0.90-0.96) in the replication cohort. All nine serum proteins of index I were found in index II. Conclusions: This study identified two circulating protein indices with the potential to discriminate between individuals with and without PDAC.
U2 - 10.1158/1078-0432.CCR-20-4215
DO - 10.1158/1078-0432.CCR-20-4215
M3 - Journal article
C2 - 33737308
AN - SCOPUS:85105351484
VL - 27
SP - 2592
EP - 2603
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 9
ER -
ID: 262850164