PhD Scientific Days 2022

Pathology and Oncology II. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Identification of Predictive Biomarkers of Enzalutamide Resistance in Metastatic Castration-Resistant Prostate Cancer

Előadó neve

Csizmarik, Anita, MSc

Előadó munkahelye

Semmelweis University Department of Urology

Előadó telefonszáma

06-30/8644513

Előadó e-mail címe

csizmarik.anita@gmail.com

Az előadás címe

Identification of Predictive Biomarkers of Enzalutamide Resistance in Metastatic Castration-Resistant Prostate Cancer

Szerző(k) neve és munkahelye

Anita Csizmarik1, Thilo Bracht2, Barbara Sitek2, Kathrin Witzke2, Martin Puhr3, Ilona Tornyi4, József Lázár5, László Takács4,5, Dávid Keresztes1, Nikolett Nagy1, Melinda Váradi1, Tamás Fazekas1, Gero Kramer6, Sabina Sevcenco6, Agnieszka Maj-Hes6, Boris Hadaschik7, Péter Nyirády1, Tibor Szarvas1,7

1 Department of Urology, Semmelweis University, Budapest, Hungary
2 Medizinisches Proteom-Center, Ruhr University Bochum, Bochum, Germany
3 Department of Urology, Medical University of Innsbruck, Innsbruck, Austria
4 Department of Human Genetics, University of Debrecen, Debrecen, Hungary
5 Biosystems International Kft, Debrecen, Hungary
6 Department of Urology, Medical University of Vienna, Vienna, Austria
7 Department of Urology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

Bemutatás módja

Szóbeli

Szekció

Pathology and Oncology II. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Language of the presentation

Hungarian

Preferred session

Pathology and Oncology

Összefoglaló szövege

Introduction: Enzalutamide (ENZA) is a next-generation androgen receptor inhibitor, which significantly prolong survival of metastatic castration-resistant prostate cancer (mCRPC) patients. Despite of clinical benefits, many of patients have baseline or acquired resistance to ENZA, however there are no validated biomarkers in the clinical practice for the prediction of treatment efficacy.
Aims: We aimed to identify proteins that are associated with ENZA-resistance and find serum biomarkers, which are involved in ENZA resistance of mCRPC.
Methods: We performed comparative proteome analysis on ENZA-resistant (DUCAP-ENZA, LAPC4-ENZA) and sensitive (DUCAP, LAPC4) prostate cancer cell lines by applying the liquid chromatography tandem mass spectrometry (LC-MS/MS) technique. We used three filtering methods in order to identify the most promising biomarker candidates. Four selected proteins (ALCAM*, AGR2, NDRG1, IDH1) were measured in baseline serum samples of 72 ENZA-treated patients by using the ELISA method. In addition, ALCAM serum levels were analyzed in 101 Abiraterone (ABI) and 100 Docetaxel (DOC)-treated mCRPC patients. Serum concentrations were correlated with clinicopathological and follow-up data.
Results: The comparative proteome analysis identified 731 significantly differentially abundant proteins between ENZA-resistant and sensitive cell lines. ELISA analysis revealed only ALCAM to be associated with poor ENZA-treated patients’ survival. Furthermore, higher baseline ALCAM levels were associated with poor survival in ABI- but not in DOC-treated patients.
Conclusion: Our results revealed that high baseline serum ALCAM levels are independently associated with poor survival in ENZA- and ABI but not in DOC-treated mCRPC patients. Therefore, ALCAM serum levels may help to select patients who less benefit from next-generation androgen signaling inhibitor treatment and may therefore help to improve therapeutic decision-making in mCRPC.
*activated leukocyte cell adhesion molecule
Funding: This work was supported by NKFIH / FK 124431. Supported by the ÚNKP-21-5-SE-3 and ÚNKP-21-3-II-SE-13 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. Tibor Szarvas was supported by a János Bolyai Research Scholarship of the Hungarian Academy of Sciences.

University and Doctoral School

Semmelweis University, Károly Rácz Doctoral School of Clinical Medicine

Supervisor

Prof. Dr. Szarvas Tibor

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4127

Start

10:00

End

10:15

Authors (legacy)

Anita Csizmarik1, Thilo Bracht2, Barbara Sitek2, Kathrin Witzke2, Martin Puhr3, Ilona Tornyi4, József Lázár5, László Takács4,5, Dávid Keresztes1, Nikolett Nagy1, Melinda Váradi1, Tamás Fazekas1, Gero Kramer6, Sabina Sevcenco6, Agnieszka Maj-Hes6, Boris Hadaschik7, Péter Nyirády1, Tibor Szarvas1,7

1 Department of Urology, Semmelweis University, Budapest, Hungary
2 Medizinisches Proteom-Center, Ruhr University Bochum, Bochum, Germany
3 Department of Urology, Medical University of Innsbruck, Innsbruck, Austria
4 Department of Human Genetics, University of Debrecen, Debrecen, Hungary
5 Biosystems International Kft, Debrecen, Hungary
6 Department of Urology, Medical University of Vienna, Vienna, Austria
7 Department of Urology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany