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001-es BibID:	BIBFORM111963
035-os BibID:	(cikkazonosító)100580 (Scopus)85165521769
Első szerző:	Lázár József
Cím:	Large-scale plasma proteome epitome profiling is an efficient tool for the discovery of cancer biomarkers / Lazar Jozsef, Antal-Szalmas Peter, Kurucz Istvan, Ferenczi Annamaria, Jozsi Mihaly, Tornyi Ilona, Muller Monika, Fekete Janos Tibor, Lamont John, FitzGerald Peter, Gall-Debreceni Anna, Kadas Janos, Vida Andras, Tardieu Nadege, Kieffer Yann, Jullien Anne, Guergova-Kuras Mariana, Hempel William, Kovacs Andras, Kardos Tamas, Bittner Nora, Csanky Eszter, Szilasi Maria, Losonczy Gyorgy, Szondy Klara, Galffy Gabriella, Csada Edit, Szalontai Klara, Somfay Attila, Malka David, Cottu Paul, Bogos Krisztina, Takacs Laszlo
Dátum:	2023
ISSN:	1535-9476
Megjegyzések:	Current proteomic technologies focus on the quantification of protein levels, while little effort is dedicated to the development of systems 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 possess dynamically changing availability of interacting surface structures frequently serve as reachable epitopes, and often carry different functions. Thus, it is highly likely, that the presence of some of the accessible epitopes correlate 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 protein epitome profiling (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. Resulting hybridoma supernatants were selected for mAb production and the corresponding hybridomas were 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.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Molecular & Cellular Proteomics. - 22 : 7 (2023), p. 1-18. -
További szerzők:	Antal-Szalmás Péter (1968-) (laboratóriumi szakorvos) Kurucz István Ferenczi Annamária (1986-) (molekuláris biológus, mikrobiológus) Józsi Mihály Tornyi Ilona (1982-) (molekuláris biológus) Müller Mónika Fekete János Tibor Lamont, John FitzGerald, Peter Gall-Debreceni Anna Kádas János (1976-) (molekuláris biológus, biokémikus, kertészmérnök) Vida András (1979-) (molekuláris biológus, genetikus) Tardieu, Nadège Kieffer, Yann Jullien, Anne Guergova-Kuras, Mariana Hempel, William Kovács András László (1969-) (biológus, biológia-kémia tanár) Kardos Tamás (1980-) (pulmonológus, klinikai onkológus) Bittner Nóra (1963-) (orvos) Csánky Eszter (1959-) (tüdőgyógyász, klinikai immunológus, allergológus) Szilasi Mária (1953-) (tüdőgyógyász, klinikai immunológus, allergológus, belgyógyász) Losonczy György Szondy Klára Gálffy Gabriella Csada Edit Szalontai Klára Somfay Attila Malka, David Cottu, Paul Bogos Krisztina Takács László (1955-) (orvos)
Pályázati támogatás:	TECH-09-A1-2009-0113; mAbCHIC Egyéb GOP-1.2.1-09-2010-0019 Egyéb
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