PhD Scientific Days 2018

Budapest, April 19–20, 2018

Identification of predictive serum biomarkers for chemotherapy resistence in prostate cancer using mass spectrometric proteome analysis

Keresztes, Dávid

Dávid Keresztes1, Thilo Bracht2, Barbara Sitek2, Martin Puhr3, Orsolya Módos1, Anita Csizmarik1, Nikolett Nagy1, Gero Kramer4, Shahrokh Shariat4, Péter Nyirády1, Tibor Szarvas1
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 Urology, Medical University of Vienna, Austria

Language of the presentation


Text of the abstract

Docetaxel (DOC) chemotherapy is a standard treatment for metastatic castration-resistant prostate cancer (CRPC). Rapidly expanding treatment options for CRPC provide reasonable alternatives for those who are resistant to DOC. Therefore, prediction of DOC-resistance has become of great clinical importance.
Our purpose is to identify protein biomarkers which may predict the efficiency of DOC-therapy.
First, a comparative proteome analysis on DOC-sensitive (parental, DU145) and resistant (DU145-DR) cell lines has been performed by using the liquid chromatography-mass spectrometry (LC-MS/MS) technique. Results were cross-referenced with published proteom data. NAMPT (nicotinamide phsophoribosyl transferase) was determined in pre-therapy serum samples of 99 DOC-treated CRPC patients by ELISA. In addition, in 25 patients serum samples before and during/at progression have been assessed. Serum NAMPT levels were correlated with clinical and survival data.
LC-MS/MS identified 157 significantly upregulated proteins in DOC-resistant DU145-DR cells. Cross-reference analysis with two published proteome data set identified four consequently upregulated proteins (NAMPT, FLNC, ANXA3, KCRB) in DOC-resistant DU145 cells. NAMPT protein level was 3.9-fold increased in DU145-DR compared to parental DU145 cells. Pre-treatment NAMPT serum levels were not associated with clinicopatological data. Cox-univariable and also multivariable analyses identified the presence of metastases, previous radical surgical treatment, high PSA and NAMPT levels as significant predictors of patients’ survival in CRPC (p=0.011, p=0.009, p=0.046 and p=0.022, respectively). NAMPT serum levels were elevated before and during/at disease progression.
Our results suggest that NAMPT might be involved in DOC resistance. Determination of serum NAMPT may contribute to the prediction of DOC-resistance and therefore may help to facilitate clinical decision-making regarding the type and timing of therapy for CRPC patients. DOC resistant patients might benefit from an early administration other systemic therapy modalities.

Data of the presenter

Doctoral school: Clinical Medicine (Beginning of the PhD studies: 09.2017)
Program: Urology (Uro-oncology)
Supervisor: Dr. Tibor Szarvas