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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
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001-es BibID:BIBFORM102408
035-os BibID:(WoS)000813770800001 (Scopus)85132153955
Első szerző:Csizmarik Anita
Cím:Proteome profiling of enzalutamide-resistant cell lines and serum analysis identified as marker of resistance in castration-resistant prostate cancer / Csizmarik Anita, Keresztes Dávid, Nagy Nikolett, Bracht Thilo, Sitek Barbara, Witzke Kathrin, Puhr Martin, Tornyi Ilona, Lázár József, Takács László, Kramer Gero, Sevcenco Sabina, Maj-Hes Agnieszka, Jurányi Zsolt, Hadaschik Boris, Nyirády Péter, Szarvas Tibor
Dátum:2022
ISSN:0020-7136
Megjegyzések:Enzalutamide (ENZA) is a frequently used therapy in metastatic castration-resistant prostate cancer (mCRPC). Baseline or acquired resistance to ENZA have been observed, but the molecular mechanisms of resistance are poorly understood. We aimed to identify proteins involved in ENZA resistance and to find therapy-predictive serum markers. We performed comparative proteome analyses on ENZA-sensitive parental (LAPC4, DuCaP) and -resistant prostate cancer cell lines (LAPC4-ENZA, DuCaP-ENZA) using liquid chromatography tandem mass spectrometry (LC-MS/MS). The top 4 most promising candidate markers were selected using bioinformatic approaches. Serum concentrations of selected markers (ALCAM, AGR2, NDRG1, IDH1) were measured in pre-treatment samples of 72 ENZA-treated mCRPC patients using ELISA. In addition, ALCAM serum levels were measured in 101 Abiraterone (ABI) and 100 Docetaxel (DOC)-treated mCRPC patients' baseline samples. Results were correlated with clinical and follow-up data. The functional role of ALCAM in ENZA resistance was assessed in vitro using siRNA. Our proteome analyses revealed 731 significantly differentially abundant proteins between ENZA-sensitive and -resistant cells and our filtering methods identified 4 biomarker candidates. Serum analyses of these proteins revealed only ALCAM to be associated with poor patient survival. Furthermore, higher baseline ALCAM levels were associated with poor survival in ABI- but not in DOC-treated patients. In LAPC4-ENZA resistant cells, ALCAM silencing by siRNA knockdown resulted in significantly enhanced ENZA sensitivity. Our analyses revealed that ALCAM serum levels may help to identify ENZA- and ABI-resistant patients and may thereby help to optimize future clinical decision-making. Our functional analyses suggest the possible involvement of ALCAM in ENZA resistance.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:International Journal Of Cancer. - 151 : 8 (2022), p. 1405-1419. -
További szerzők:Keresztes Dávid Nagy Nikoletta 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 Jurányi Zsolt Hadaschik, Boris Nyirády Péter Szarvas Tibor (urológus)
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3.

001-es BibID:BIBFORM093453
Első szerző:Csizmarik Anita
Cím:Comparative proteome analysis identified ALCAM as a potential serum biomarker for enzalutamide resistance in castration-resistant prostate cancer / Anita Csizmarik, Thilo Bracht, Barbara Sitek, Kathrine Witzke, Martin Puhr, Ilona Tornyi, József Lázár, László Takács, Dávid Keresztes, Nikolett Nagy, Melinda Váradi, Gero Kramer, Sabina Sevcenco, Agnieszka Maj-Hes, Shahrokh F. Shariat, Boris Hadaschik, Péter Nyirády, Tibor Szarvas
Dátum:2020
Megjegyzések:PhD Scientific Days 2020 (2020)(Budapest). PhD scientific days 2020 / Poster presentations: Molecular Sciences I. Posters
Tárgyszavak:Orvostudományok Klinikai orvostudományok nem besorolt
egyéb
További szerzők:Bracht, Thilo Sitek Barbara Witzke, Kathrin Puhr, Martin Tornyi Ilona (1982-) (molekuláris biológus) Lázár József Takács László Keresztes Dávid Nagy Nikoletta Váradi Melinda Kramer, Gero Sevcenko, Sabina Maj-Hes, Agnieszka Shariat, Sharokh Hadaschik, Boris Nyirády Péter Szarvas Tibor (matematikus informatikus)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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