دورية أكاديمية
أعرض في EDS

Development and validation of circulating protein signatures as diagnostic biomarkers for biliary tract cancer.

التفاصيل البيبلوغرافية
العنوان: Development and validation of circulating protein signatures as diagnostic biomarkers for biliary tract cancer.
المؤلفون: Christensen TD; Deparment of Oncology, Copenhagen University Hospital - Herlev and Gentofte Hospital, Herlev, Denmark., Maag E; BioXpedia, Aarhus, Denmark., Larsen O; Deparment of Oncology, Copenhagen University Hospital - Herlev and Gentofte Hospital, Herlev, Denmark., Feltoft CL; Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte Hospital, Herlev, Denmark., Nielsen KR; Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark., Jensen LH; Department of Oncology, University Hospital of Southern Denmark, Vejle, Denmark., Leerhøy B; Digestive Disease Center, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark., Hansen CP; Department of Surgery, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Chen IM; Deparment of Oncology, Copenhagen University Hospital - Herlev and Gentofte Hospital, Herlev, Denmark., Nielsen DL; Deparment of Oncology, Copenhagen University Hospital - Herlev and Gentofte Hospital, Herlev, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Johansen JS; Deparment of Oncology, Copenhagen University Hospital - Herlev and Gentofte Hospital, Herlev, Denmark.; Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte Hospital, Herlev, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
المصدر: JHEP reports : innovation in hepatology [JHEP Rep] 2022 Dec 13; Vol. 5 (3), pp. 100648. Date of Electronic Publication: 2022 Dec 13 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101761237 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-5559 (Electronic) Linking ISSN: 25895559 NLM ISO Abbreviation: JHEP Rep Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Amsterdam] : Elsevier B.V., [2019]-
مستخلص: 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 with biliary tract cancer from those without cancer. Several profiles were found and tested in different groups of patients. The profiles were successful at identifying most patients with biliary tract cancer, pointing towards the utility of multiprotein signatures in this context.
Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.
(© 2022 The Author(s).)
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فهرسة مساهمة: Keywords: AUC, area under receiver-operating characteristic curve; BBTD, benign biliary tract disease; BP, best point; BTC, biliary tract cancer; CA19-9, carbohydrate antigen 19-9; CAIX, carbonic anhydrase IX; CASP8, caspase 8; CCA, cholangiocarcinoma; CCL, chemokine (C-C motif) ligand; CXCR, C-X-C motif chemokine; EDTA, ethylenediaminetetraacetic acid; GBC, gall bladder cancer; I-O, immuno-oncology; IL, interleukin; MMP-, matrix metalloproteinase-; NPX, normalized protein expression; TME, tumor microenvironment; biliary tract cancer; blood protein assay; cholangiocarcinoma; dCCA, distal cholangiocarcinoma; diagnosis; gall bladder cancer; iCCA, intrahepatic cholangiocarcinoma; multi-biomarker signature; pCCA, perihilar cholangiocarcinoma
تواريخ الأحداث: Date Created: 20230126 Latest Revision: 20230202
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC9867981
DOI: 10.1016/j.jhepr.2022.100648
PMID: 36699667
قاعدة البيانات: MEDLINE
الوصف
تدمد:2589-5559
DOI:10.1016/j.jhepr.2022.100648