Matrix metalloproteinase 7, soluble Fas and Fas ligand serum levels for predicting docetaxel resistance and survival in castration-resistant prostate cancer

Tibor Szarvas, Sabina Sevcenco, Orsolya Módos, Dávid Keresztes, Péter Nyirády, Anita Csizmarik, Robin Ristl, Martin Puhr, Michèle J. Hoffmann, Christian Niedworok, Boris Hadaschik, Agnieszka Maj-Hes, Shahrokh F. Shariat, Gero Kramer

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2 Citations (Scopus)

Abstract

Objective: To assess the predictive value of pre-chemotherapy matrix metalloproteinase 7 (MMP-7), soluble Fas (sFas) and Fas ligand (FasL) serum levels, as well as their changes during therapy. Patients and Methods: Serum levels of MMP-7, Fas and FasL were determined by ELISA in 96 patients with castration-resistant prostate cancer (CRPC): 21 docetaxel-resistant patients who received one single series and 75 docetaxel-sensitive patients who received repeated series of docetaxel. In addition to the 96 pretreatment serum samples, 987 sera collected during chemotherapy were also analysed. Results: Higher pretreatment serum MMP-7, sFas and prostate-specific antigen (PSA) levels were significantly associated with both docetaxel resistance (P = 0.007, P = 0.001, P < 0.001, respectively) and shorter cancer-specific survival (P < 0.001, P = 0.041, P < 0.001, respectively). High MMP-7 level remained an independent predictor of both docetaxel resistance (hazard ratio [HR] 2.298, 95% confidence interval [CI]: 1.354–3.899; P = 0.002) and poor cancer-specific survival (HR 2.11, 95% CI: 1.36–3.30; P = 0.001) in multivariable analyses. Greater increase in MMP-7 levels in the second treatment holiday and greater increase in PSA levels in the first and second treatment holidays were predictive of survival. Conclusions: Pretreatment serum MMP-7 levels may help to select patients with CRPC who are likely to benefit from docetaxel chemotherapy. Furthermore, MMP-7 levels alone or in combination with PSA levels could be used for therapy monitoring. Correlative studies embedded in clinical trials are necessary to validate these biomarkers for clinical decision-making.

Original languageEnglish
Pages (from-to)695-704
Number of pages10
JournalBJU International
Volume122
Issue number4
DOIs
Publication statusPublished - Oct 2018

Keywords

  • #ProstateCancer
  • #pcsm
  • Fas
  • MMP-7
  • docetaxel
  • prognosis
  • serum

ASJC Scopus subject areas

  • Urology

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    Szarvas, T., Sevcenco, S., Módos, O., Keresztes, D., Nyirády, P., Csizmarik, A., Ristl, R., Puhr, M., Hoffmann, M. J., Niedworok, C., Hadaschik, B., Maj-Hes, A., Shariat, S. F., & Kramer, G. (2018). Matrix metalloproteinase 7, soluble Fas and Fas ligand serum levels for predicting docetaxel resistance and survival in castration-resistant prostate cancer. BJU International, 122(4), 695-704. https://doi.org/10.1111/bju.14415