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001-es BibID:	BIBFORM114434
035-os BibID:	(Scopus)85169116190 (WoS)001063702100001
Első szerző:	Csizmarik Anita
Cím:	Comparative proteome and serum analysis identified FSCN1 as a marker of abiraterone resistance in castration-resistant prostate cancer / Csizmarik Anita, Nagy Nikolett, Keresztes Dávid, Váradi Melinda, Bracht Thilo, Sitek Barbara, Witzke Kathrin, Puhr Martin, Tornyi Ilona, Lázár József, Takács László, Kramer Gero, Sevcenco Sabina, Maj-Hes Agnieszka, Hadaschik Boris, Nyirády Péter, Szarvas Tibor
Dátum:	2023
ISSN:	1365-7852
Megjegyzések:	Background: Abiraterone (Abi) is an androgen receptor signaling inhibitor that significantly improves patients' life expectancy in metastatic prostate cancer (PCa). Despite its beneficial effects, many patients have baseline or acquired resistance against Abi. The aim of this study was to identify predictive serum biomarkers for Abi treatment. Methods: We performed a comparative proteome analysis on three Abi sensitive (LNCaPabl, LAPC4, DuCaP) and resistant (LNCaPabl-Abi, LAPC4-Abi, DuCaP-Abi) PCa cell lines using liquid chromatography tandem mass spectrometry (LC-MS/MS) technique. Two bioinformatic selection workflows were applied to select the most promising candidate serum markers. Serum levels of selected proteins were assessed in samples of 100 Abi-treated patients with metastatic castration-resistant disease (mCRPC) using ELISA. Moreover, FSCN1 serum concentrations were measured in samples of 69 Docetaxel (Doc) treated mCRPC patients. Results: Our proteome analysis identified 68 significantly, at least two-fold upregulated proteins in Abi resistant cells. Using two filtering workflows four proteins (AMACR, KLK2, FSCN1 and CTAG1A) were selected for ELISA analyses. We found high baseline FSCN1 serum levels to be significantly associated with poor survival in Abi-treated mCRPC patients. Moreover, the multivariable analysis revealed that higher ECOG status (>1) and high baseline FSCN1 serum levels (>10.22 ng/ml by ROC cut-off) were independently associated with worse survival in Abi-treated patients (p < 0.001 and p = 0.021, respectively). In contrast, no association was found between serum FSCN1 concentrations and overall survival in Doc-treated patients. Conclusions: Our analysis identified baseline FSCN1 serum levels to be independently associated with poor survival of Abi-treated, but not Doc-treated mCRPC patients, suggesting a therapy specific prognostic value for FSCN1.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Prostate Cancer And Prostatic Diseases. - [Epub ahead of print] (2023). -
További szerzők:	Nagy Nikoletta Keresztes Dávid Váradi Melinda Bracht, Thilo Sitek Barbara Witzke, Kathrin Puhr, Martin Tornyi Ilona (1982-) (molekuláris biológus) Lázár József Takács László (1955-) (orvos) Kramer, Gero Sevcenko, Sabina Maj-Hes, Agnieszka Hadaschik, Boris Nyirády Péter Szarvas Tibor (urológus)
Pályázati támogatás:	NKFIH / FK 124431 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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