دورية أكاديمية
Development and validation of circulating protein signatures as diagnostic biomarkers for biliary tract cancer
العنوان: | Development and validation of circulating protein signatures as diagnostic biomarkers for biliary tract cancer |
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المؤلفون: | Troels D. Christensen, Emil Maag, Ole Larsen, Claus L. Feltoft, Kaspar René Nielsen, Lars Henrik Jensen, Bonna Leerhøy, Carsten P. Hansen, Inna M. Chen, Dorte L. Nielsen, Julia S. Johansen |
المصدر: | JHEP Reports, Vol 5, Iss 3, Pp 100648- (2023) |
بيانات النشر: | Elsevier |
سنة النشر: | 2023 |
المجموعة: | Directory of Open Access Journals: DOAJ Articles |
مصطلحات موضوعية: | biliary tract cancer, cholangiocarcinoma, gall bladder cancer, blood protein assay, multi-biomarker signature, diagnosis, Diseases of the digestive system. Gastroenterology, RC799-869 |
الوصف: | Background & Aims: Biliary tract cancer (BTC) is associated with a dismal prognosis, partly because it is typically diagnosed late, highlighting the need for diagnostic biomarkers. The purpose of this project was to identify and validate multiprotein signatures that could differentiate patients with BTC from non-cancer controls. Methods: In this study, we included treatment-naïve patients with BTC, healthy controls, and patients with benign conditions including benign biliary tract disease. Participants were divided into three non-overlapping cohorts: a case-control-based discovery cohort (BTC = 186, controls = 249); a case-control-based validation cohort (validation cohort 1: BTC = 113, controls = 241); and a cohort study-based validation cohort including participants (BTC = 8, controls = 132) referred for diagnostic work-up for suspected cancer (validation cohort 2). Immuno-Oncology (I-O)-related proteins were measured in serum and plasma using a proximity extension assay (Olink Proteomics). Lasso and Ridge regressions were used to generate protein signatures of I-O-related proteins and carbohydrate antigen 19-9 (CA19-9) in the discovery cohort. Results: Sixteen protein signatures, including 2 to 82 proteins, were generated. All signatures included CA19-9 and chemokine C-C motif ligand 20. Signatures discriminated between patients with BTC vs. controls, with AUCs ranging from 0.95 to 0.99 in the discovery cohort and 0.94 to 0.97 in validation cohort 1. In validation cohort 2, AUCs ranged from 0.84 to 0.94. Nine signatures achieved a specificity of 82% to 84% while keeping a sensitivity of 100% in validation cohort 2. All signatures performed better than CA19-9, and signatures including >15 proteins showed the best performance. Conclusion: The study demonstrated that it is possible to generate protein signatures that can successfully differentiate patients with BTC from non-cancer controls. Impact and implications: We attempted to find blood sample-based protein profiles that could differentiate patients ... |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
تدمد: | 2589-5559 |
العلاقة: | http://www.sciencedirect.com/science/article/pii/S2589555922002208Test; https://doaj.org/toc/2589-5559Test; https://doaj.org/article/51bf95d915174913b37fd8a23ae83013Test |
DOI: | 10.1016/j.jhepr.2022.100648 |
الإتاحة: | https://doi.org/10.1016/j.jhepr.2022.100648Test https://doaj.org/article/51bf95d915174913b37fd8a23ae83013Test |
رقم الانضمام: | edsbas.C59BC94F |
قاعدة البيانات: | BASE |
تدمد: | 25895559 |
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DOI: | 10.1016/j.jhepr.2022.100648 |