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

Szarvas, Tibor and Sevcenco, Sabina and Módos, Orsolya and Keresztes, Dávid and Nyirády, Péter and Csizmarik, Anita (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). pp. 695-704. ISSN 1464-4096 (print); 1464-410X (online)

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Abstract

PURPOSE: To assess the predictive value of pre-chemotherapy MMP-7, sFas, 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 CRPC patients; 21 docetaxel-resistant who received one single series and 75 docetaxel-sensitive 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 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 remained an independent predictor of both docetaxel resistance (HR: 2.298, 95% CI: 1.354-3.899, p=0.002) and poor cancer-specific survival (HR=2.11, 95%Cl 1.36-3.30, p=0.001) in multivariable analyses. Higher increase of MMP-7 levels in the 2(nd) treatment holiday and higher increase of PSA levels in the 1(st) and 2(nd) holidays were predictive of survival. CONCLUSIONS: Pretreatment serum MMP-7 levels may help to select CRPC patients who are likely to benefit from docetaxel chemotherapy. Furthermore, MMP-7 alone or in combination with PSA could be used for therapy monitoring. Correlative studies embedded in clinical trials are necessary to validate these biomarkers for clinical decision-making. This article is protected by copyright. All rights reserved.

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