PhD Scientific Days 2020

Molecular Sciences II. Posters

NAMPT and CD44 as Possible Serum Biomarkers in Docetaxel-Resistance of Castration Resistant Prostate Cancer

Előadó neve

Keresztes, Dávid, MSc

Előadó munkahelye

Semmelweis University, Department of Urology

Előadó telefonszáma

+36207752205

Előadó e-mail címe

keresztes.david@outlook.com

Az előadás címe

NAMPT and CD44 as Possible Serum Biomarkers in Docetaxel-Resistance of Castration Resistant Prostate Cancer

Szerző(k) neve és munkahelye

Dávid Keresztes1, Orsolya Módos1, Miklós Szűcs1, András Hüttl1, Anita Csizmarik1, Nikolett Nagy1, Melinda Váradi1, Thilo Bracht2, Barbara Sitek2, Kathrin Witzke2, Martin Puhr3, Sabina Sevcenko4, Gero Kramer5, Shahrokh Shariat5, László Takács6,7, Ilona Tornyi6, József Lázár7, Péter Nyirády1, Tibor Szarvas1

1 Semmelweis Egyetem, Urológiai Klinika, Budapest
2 Ruhr University, Medizinisches Proteom-Center, Bochum
3 Medizinische Universität Innsbruck, Klinik für Urologie, Innsbruck
4 Medizinische Universität Wien, Universitätsklinik für Urologie, Vienna
5 Medical University of Vienna, Dept. of Urology, Vienna
6 Debreceni Egyetem, Humángenetikai Tanszék, Debrecen
7 Biosystems International Kft, Debrecen

Szekció

Molecular Sciences II. Posters

Language of the presentation

Hungarian

Section, first choice

Molecular Sciences

Section, second choice

Pathology and Oncology

Összefoglaló szövege

Introduction:
Docetaxel (DOC) chemotherapy is still one of the standard first-line therapies in metastatic castration-resistant prostate cancer (CRPC) but most of the patients have baseline or will acquire resistance to this treatment. At the same time, novel therapeutic agents provide reasonable alternatives for DOC-resistant patients. Therefore, prediction of DOC-resistance has become clinically important in order to optimize therapy decisions.

Aims:
Our aim is to identify serum-biomarkers which are able to select patients who will not benefit from DOC treatment.

Methods:
DOC-sensitive (PC3; DU145) and resistant (PC3-DR; DU145-DR) prostate cancer cell lines were comparatively analysed by the liquid chromatography tandem mass spectrometry (LC-MS/MS) technique. Results were processed using bioinformatic methods in order to identify promising biomarker candidates. Serum levels of six selected proteins (NAMPT, CD44, HGFR, LNPEP, GSN, IL13RA2) were measured in pretreatment and follow-up serum samples of DOC-treated CRPC patients by ELISA. Serum levels were correlated with clinicopathological and follow-up data.

Results:
Proteome analysis identified 177 at least two-fold, significantly overexpressed proteins in DOC-resistant cell lines. Applying our bionformatic approach, six serum proteins were selected for further investigations. Higher NAMPT and CD44 serum levels showed significant correlations with poor patients’ survival (p=0.012 and p=0.021, respectively). The multivariate model revealed the presence of metastases, higher pretreatment PSA, CD44 and NAMPT serum levels as independent predictors of poor survival in DOC-treated CRPC patients. Furthermore, NAMPT serum levels were significantly higher before (median= 2.87 ng/ml) and at radiograpic diesease progression (3.27 ng/ml) compared to baseline values (1.62 ng/ml).

Conclusions:
Our results imply that serum NAMPT and CD44 levels might be used as biomarkers for the identification of DOC-resistant patients and may therefore help to optimize future clinical decision-making regarding the type and timing of other treatments for CRPC patients. Functional experiments using cell culture techniques with gene silencing are currently ongoing in order to assess the possible functional involvement of NAMPT and CD44 in DOC-resistance.

Additional Information

Doctoral School: Clinical Medicine
Program: Urology
Supervisor: Tibor Szarvas
E-mail: keresztes.david@outlook.com
Poster presentation

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

2795

Start

13:05

End

13:08

Authors (legacy)

Dávid Keresztes1, Orsolya Módos1, Miklós Szűcs1, András Hüttl1, Anita Csizmarik1, Nikolett Nagy1, Melinda Váradi1, Thilo Bracht2, Barbara Sitek2, Kathrin Witzke2, Martin Puhr3, Sabina Sevcenko4, Gero Kramer5, Shahrokh Shariat5, László Takács6,7, Ilona Tornyi6, József Lázár7, Péter Nyirády1, Tibor Szarvas1

1 Semmelweis Egyetem, Urológiai Klinika, Budapest
2 Ruhr University, Medizinisches Proteom-Center, Bochum
3 Medizinische Universität Innsbruck, Klinik für Urologie, Innsbruck
4 Medizinische Universität Wien, Universitätsklinik für Urologie, Vienna
5 Medical University of Vienna, Dept. of Urology, Vienna
6 Debreceni Egyetem, Humángenetikai Tanszék, Debrecen
7 Biosystems International Kft, Debrecen