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Matrix metalloproteinase 7, soluble Fas and Fas ligand serum levels for predicting docetaxel resistance and survival in castration‐resistant prostate cancer
Author(s) -
Szarvas Tibor,
Sevcenco Sabina,
Módos Orsolya,
Keresztes Dávid,
Nyirády Péter,
Csizmarik Anita,
Ristl Robin,
Puhr Martin,
Hoffmann Michèle J.,
Niedworok Christian,
Hadaschik Boris,
MajHes Agnieszka,
Shariat Shahrokh F.,
Kramer Gero
Publication year - 2018
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.14415
Subject(s) - docetaxel , medicine , prostate cancer , oncology , chemotherapy , hazard ratio , fas ligand , cancer , prostate specific antigen , confidence interval , urology , apoptosis , biology , programmed cell death , biochemistry
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.