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Circulating Protein Biomarkers for Use in Pancreatic Ductal Adenocarcinoma Identification

医学 队列 内科学 胰腺癌 胰腺导管腺癌 胃肠病学 置信区间 CA19-9号 前瞻性队列研究 阶段(地层学) 生物标志物 癌症 腺癌 病理 肿瘤科 生物 古生物学 生物化学
作者
Sidsel C. Lindgaard,Zsofia Sztupinszki,Emil Maag,Inna M. Chen,Astrid Z. Johansen,Benny Vittrup Jensen,Stig E. Bojesen,Dorte Nielsen,Carsten Palnæs Hansen,Jane P. Hasselby,Kaspar René Nielsen,Zoltan Szallasi,Julia S. Johansen
出处
期刊:Clinical Cancer Research [American Association for Cancer Research]
卷期号:27 (9): 2592-2603 被引量:13
标识
DOI:10.1158/1078-0432.ccr-20-4215
摘要

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.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.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.This study identified two circulating protein indices with the potential to discriminate between individuals with and without PDAC.
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