PhD Scientific Days 2020

Molecular Sciences I. Posters

Comparative Proteome Analysis Identified ALCAM as a Potential Serum Biomarker for Enzalutamide Resistance in Castration-Resistant Prostate Cancer

Előadó neve

Csizmarik, Anita

Előadó munkahelye

Semmelweis University, Department of Urology

Előadó telefonszáma

06-30/8644513

Előadó e-mail címe

csizmarik.anita@gmail.com

Az előadás címe

Comparative Proteome Analysis Identified ALCAM as a Potential Serum Biomarker for Enzalutamide Resistance in Castration-Resistant Prostate Cancer

Szerző(k) neve és munkahelye

Anita Csizmarik1, Thilo Bracht2, Barbara Sitek2, Kathrine Witzke2, Martin Puhr3, Ilona Tornyi4, József Lázár5, László Takács4,5, Dávid Keresztes1, Nikolett Nagy1, Melinda Váradi1, Gero Kramer6, Sabina Sevcenco6, Agnieszka Maj-Hes6, Shahrokh F. Shariat6, Boris Hadaschik7, Péter Nyirády1, Tibor Szarvas1,7

1 Department of Urology, Semmelweis University, Budapest, Hungary
2 Medizinisches Proteom-Center, Ruhr University Bochum, Germany
3 Department of Urology, Medical University of Innsbruck, Austria
4 Department of Human Genetics, University of 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, Germany

Szekció

Molecular Sciences I. Posters

Language of the presentation

Hungarian

Section, first choice

Molecular Sciences

Section, second choice

Pathology and Oncology

Összefoglaló szövege

Introduction: Enzalutamide (ENZA) is a second-generation androgen receptor inhibitor, which has been approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Despite of clinical benefits, many of patients have baseline or acquired resistance to ENZA, however the molecular mechanisms of resistance are not completely understood.

Aims: We aimed to identify potential serum biomarkers, which are involved in ENZA resistance of mCRPC.

Methods: ENZA-resistant (LNCaPabl-ER, DUCaP-ER, LAPC4-ER) and sensitive (LNCaPabl, DUCaP, LAPC4) prostate cancer cell lines were comparatively analysed by applying the liquid chromatography tandem mass spectrometry (LC-MS/MS) technique. The most promising biomarker candidates were identified by using three different bioinformatic approaches. Six selected proteins (ALCAM*, AGR2, NDRG1, RRM2, GR, IDH1) were analysed in baseline serum samples of 72 ENZA-treated patients by using the ELISA method. Serum biomarker concentrations were correlated with clinicopathological and follow-up data.

Results: Our comparative proteome analysis identified 278 at least two-fold, significantly upregulated proteins in ENZA-resistant cell lines. Five of the six examined proteins were detectable in patients’ serum samples. High ALCAM serum levels were significantly associated with shorter overall survival. Multivariable analyses revealed the presence of bone metastases, high PSA and ALCAM levels as independent predictors of poor patients’ survival in ENZA-treated CRPC patients (p=0.021, p=0.021 and p=0.012, respectively).

Conclusions: Our results imply that ALCAM serum levels may help to select patients who less benefit from ENZA-treatment and may therefore help to improve therapeutic decision-making in CRPC. Currently, we are working on functional knock-down analyses of ALCAM protein in cell culture in order to assess its role in ENZA resistance. Additionally, further upregulated proteins will be selected and analysed as candidate predictive serum markers.
*activated leukocyte cell adhesion molecule

Additional Information

Doctoral School: Clinical Medicine
Program: Urology
Supervisor: Tibor Szarvas
E-mail address: csizmarik.anita@gmail.com
poster presentation

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4127

Start

11:32

End

11:35

Authors (legacy)

Anita Csizmarik1, Thilo Bracht2, Barbara Sitek2, Kathrine Witzke2, Martin Puhr3, Ilona Tornyi4, József Lázár5, László Takács4,5, Dávid Keresztes1, Nikolett Nagy1, Melinda Váradi1, Gero Kramer6, Sabina Sevcenco6, Agnieszka Maj-Hes6, Shahrokh F. Shariat6, Boris Hadaschik7, Péter Nyirády1, Tibor Szarvas1,7

1 Department of Urology, Semmelweis University, Budapest, Hungary
2 Medizinisches Proteom-Center, Ruhr University Bochum, Germany
3 Department of Urology, Medical University of Innsbruck, Austria
4 Department of Human Genetics, University of 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, Germany