Large-Scale Plasma Proteome Epitome Profiling is an Efficient Tool for the Discovery of Cancer Biomarkers.

Autor:	Lazar J; Biosystems International Kft., Debrecen, Hungary; Biosystems Immunolab Zrt., Debrecen, Hungary. Electronic address: jozsef.lazar@biosys-ilab.com., Antal-Szalmas P; Biosystems Immunolab Zrt., Debrecen, Hungary; Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Kurucz I; Biosystems International Kft., Debrecen, Hungary; Biosystems Immunolab Zrt., Debrecen, Hungary., Ferenczi A; Biosystems International Kft., Debrecen, Hungary., Jozsi M; Department of Immunology, ELTE Eötvös Loránd University, Budapest, Hungary; MTA-ELTE Complement Research Group, Eötvös Loránd Research Network (ELKH), Budapest, Hungary., Tornyi I; Biosystems Immunolab Zrt., Debrecen, Hungary; Department of Human Genetics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Muller M; Adware Research Kft., Balatonfüred, Hungary., Fekete JT; Department of Bioinformatics, Semmelweis University, Budapest, Hungary., Lamont J; Randox Laboratories Ltd, Crumlin, United Kingdom., FitzGerald P; Randox Laboratories Ltd, Crumlin, United Kingdom., Gall-Debreceni A; Biosystems International Kft., Debrecen, Hungary., Kadas J; Biosystems International Kft., Debrecen, Hungary., Vida A; Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Tardieu N; Biosystems International SAS, Evry, France., Kieffer Y; Biosystems International SAS, Evry, France., Jullien A; Biosystems International SAS, Evry, France., Guergova-Kuras M; Biosystems International SAS, Evry, France., Hempel W; Biosystems International SAS, Evry, France., Kovacs A; Biosystems Immunolab Zrt., Debrecen, Hungary., Kardos T; Department of Pulmonology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Bittner N; Department of Pulmonology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Csanky E; Department of Pulmonology, Miskolc Semmelweis Hospital and University Hospital, Miskolc, Hungary., Szilasi M; Department of Pulmonology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Losonczy G; Department of Pulmonology, Faculty of Medicine, Semmelweis University, Budapest, Hungary., Szondy K; Department of Pulmonology, Faculty of Medicine, Semmelweis University, Budapest, Hungary., Galffy G; Department of Pulmonology, Faculty of Medicine, Semmelweis University, Budapest, Hungary., Csada E; Csongrád County Hospital of Chest Diseases, Deszk, Hungary., Szalontai K; Csongrád County Hospital of Chest Diseases, Deszk, Hungary., Somfay A; Department of Pulmonology, Faculty of Medicine, University of Szeged, Deszk, Hungary., Malka D; Department of Medical Oncology, Gustave Roussy, Villejuif, France., Cottu P; Department of Medical Oncology, Institut Curie, Paris, France., Bogos K; National Koranyi Institute for Pulmonology, Budapest, Hungary., Takacs L; Biosystems International Kft., Debrecen, Hungary; Biosystems Immunolab Zrt., Debrecen, Hungary; Department of Human Genetics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; Biosystems International SAS, Evry, France. Electronic address: laszlo.takacs@biosys-ilab.com.
Jazyk:	angličtina
Zdroj:	Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2023 Jul; Vol. 22 (7), pp. 100580. Date of Electronic Publication: 2023 May 20.
DOI:	10.1016/j.mcpro.2023.100580
Abstrakt:	Current proteomic technologies focus on the quantification of protein levels, while little effort is dedicated to the development of system approaches to simultaneously monitor proteome variability and abundance. Protein variants may display different immunogenic epitopes detectable by monoclonal antibodies. Epitope variability results from alternative splicing, posttranslational modifications, processing, degradation, and complex formation and possesses dynamically changing availability of interacting surface structures that frequently serve as reachable epitopes and often carry different functions. Thus, it is highly likely that the presence of some of the accessible epitopes correlates with function under physiological and pathological conditions. To enable the exploration of the impact of protein variation on the immunogenic epitome first, here, we present a robust and analytically validated PEP technology for characterizing immunogenic epitopes of the plasma. To this end, we prepared mAb libraries directed against the normalized human plasma proteome as a complex natural immunogen. Antibody producing hybridomas were selected and cloned. Monoclonal antibodies react with single epitopes, thus profiling with the libraries is expected to profile many epitopes which we define by the mimotopes, as we present here. Screening blood plasma samples from control subjects (n = 558) and cancer patients (n = 598) for merely 69 native epitopes displayed by 20 abundant plasma proteins resulted in distinct cancer-specific epitope panels that showed high accuracy (AUC 0.826-0.966) and specificity for lung, breast, and colon cancer. Deeper profiling (≈290 epitopes of approximately 100 proteins) showed unexpected granularity of the epitope-level expression data and detected neutral and lung cancer-associated epitopes of individual proteins. Biomarker epitope panels selected from a pool of 21 epitopes of 12 proteins were validated in independent clinical cohorts. The results demonstrate the value of PEP as a rich and thus far unexplored source of protein biomarkers with diagnostic potential. Competing Interests: Conflict of interest The authors declare no conflict of interest. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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