Circulating syndecan-1 is associated with chemotherapy-resistance in castration-resistant prostate cancer

Abstract

OBJECTIVES: Docetaxel chemotherapy is a standard treatment for castration-resistant prostate cancer (CRPC). Rapidly expanding treatment options for CRPC provide reasonable alternatives for those who are resistant to docetaxel. Therefore, prediction of docetaxel resistance has become of great clinical importance. Syndecan-1 (SDC1) has been currently shown to be involved in chemotherapy resistance in various malignancies including prostate cancer. The predicting value of serum SDC1 level has not been evaluated yet. PATIENTS AND METHODS: We assessed the baseline levels of SDC1 in serum samples of 75 patients with CRPC who received docetaxel therapy until the appearance of therapy resistance. In one patient who was treated with three treatment series, we assessed also 6 additional serum samples collected during a 1-year treatment period. Serum SDC1 levels were correlated with clinical outcomes as well as with serum levels of MMP7. RESULTS: Pretreatment SDC1 serum levels were not associated with patients' age, the presence of bone or visceral metastases. In univariable analyses, patients' performance status, the presence of bone or visceral metastases, high pretreatment prostate specific antigen and SDC1 levels were significantly associated with cancer-specific survival. In multivariable analysis patients' performance status (P = 0.005), presence of bone or visceral metastases (P = 0.013) and high SDC1 level (P = 0.045) remained independent predictors of patients' survival. In the patient with available follow-up samples serum SDC1 level increased from 50 to 300ng/ml at radiographic progression. Serum concentrations of SDC1 were correlated with those of MMP7 (r = 0.420, P = 0.006). CONCLUSIONS: Our present results together with currently published data suggest a role for SDC1 shedding in chemotherapy resistance. Determination of serum SDC1 may contribute to the prediction of docetaxel resistance and therefore may help to facilitate clinical decision-making regarding the type and timing of therapy for patients with CRPC.