Matrix metalloproteinase 7, soluble Fas and Fas ligand serum levels for predicting docetaxel resistance and survival in castration-resistant prostate cancer.
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.
['Szarvas|Tibor|T|0000-0002-6321-0799', 'Sevcenco|Sabina|S|', 'Módos|Orsolya|O|', 'Keresztes|Dávid|D|', 'Nyirády|Péter|P|', 'Csizmarik|Anita|A|', 'Ristl|Robin|R|', 'Puhr|Martin|M|', 'Hoffmann|Michèle J|MJ|', 'Niedworok|Christian|C|', 'Hadaschik|Boris|B|', 'Maj-Hes|Agnieszka|A|', 'Shariat|Shahrokh F|SF|', 'Kramer|Gero|G|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000970:Antineoplastic Agents D000971:Antineoplastic Combined Chemotherapy Protocols D015331:Cohort Studies D000077143:Docetaxel D019008:Drug Resistance, Neoplasm D053222:Fas Ligand Protein D006801:Humans D008297:Male D020783:Matrix Metalloproteinase 7 D008875:Middle Aged D011237:Predictive Value of Tests D017430:Prostate-Specific Antigen D064129:Prostatic Neoplasms, Castration-Resistant D016019:Survival Analysis D016896:Treatment Outcome
Fas serum docetaxel MMP-7 #ProstateCancer #pcsm prognosis