The prognostic value of serum MMP-7 levels in prostate cancer patients who received docetaxel, abiraterone, or enzalutamide therapy.

OBJECTIVES: The rapidly changing treatment landscape in metastatic castration-resistant prostate cancer (mCRPC) calls for biomarkers to guide treatment decisions. We recently identified MMP-7 as a potential serum marker for the prediction of response and survival in mCRPC patients who received docetaxel (DOC) chemotherapy. Here, we aimed to test this finding in an independent patient cohort and in addition to explore the prognostic potential of serum MMP-7 in abiraterone (ABI) or enzalutamide (ENZA) treated patients. METHODS AND MATERIALS: MMP-7 levels were measured in 836 serum samples from 320 mCRPC patients collected before and during DOC (n = 95), ABI (n = 140), or ENZA (n = 85) treatment by using the ELISA method. Results were correlated with clinical and follow-up data. RESULTS: MMP-7 baseline levels were similar between the 3 treatment groups. In the ABI and ENZA cohorts, baseline MMP-7 levels were lower in patients with prior radical prostatectomy (P = 0.058 and P = 0.041, respectively). Baseline MMP-7 levels above the median were associated with shorter overall survival for the DOC (P = 0.001) and ENZA (P = 0.006) cohorts. Multivariable analyses in the DOC and ENZA cohorts revealed that high pretreatment MMP-7 level is an independent risk factor for patients' survival. In addition, in DOC-treated patients with high baseline MMP-7 level, marker decrease at the third DOC cycle was associated with improved survival. Patients with high baseline MMP-7 levels had better survival when treated with ABI compared to DOC or ENZA. CONCLUSIONS: We confirmed the prognostic value of pretreatment MMP-7 serum level and its changes as independent predictors of survival in DOC-treated mCRPC patients. In addition, high MMP-7 was a negative predictor in ENZA-treated but not in ABI-treated patients. These results warrant further research to confirm the predictive value of serum MMP-7 and to explore the potential mechanistic involvement of MMP-7 in DOC and ENZA resistance of mCRPC patients.

High-soluble CGA levels are associated with poor survival in bladder cancer.

Recently, a neuroendocrine-like molecular subtype has been discovered in muscle-invasive urothelial bladder cancer (BC). Chromogranin A (CGA) is a widely used tissue and serum marker in neuroendocrine tumors. Our aim was to evaluate serum CGA (sCGA) concentrations and their associations with clinical and follow-up data in BC and renal cell carcinoma (RCC). sCGA concentrations were analyzed in the following cohorts: (1) BC training set (n = 188), (2) BC validation set (n = 125), (3) RCC patients (n = 77), (4) healthy controls (n = 97). CGA immunohistochemistry and RT-qPCR analyses were performed in 20 selected FFPE and 29 frozen BC tissue samples. Acquired data were correlated with clinicopathological parameters including comorbidities with known effect on sCGA as well as with patients' follow-up data. sCGA levels were significantly higher in BC but not in RCC patients compared to healthy controls. High sCGA levels were independently associated with poor overall and disease-specific survival both in the BC training (P < 0.001, P = 0.002) and validation set (P = 0.009, P = 0.017). sCGA levels were inversely correlated with glomerulus filtrating rate (GFR) and linearly correlated with creatinine clearance and urea concentrations. These correlations were not related to the prognostic value of sCGA. Tissue CGA levels were low to absent independently of sCGA concentrations. Our results demonstrate elevated levels and an independent prognostic value for sCGA in BC but not in RCC. Despite the significant correlation between sCGA and GFR, the prognostic relevance of sCGA seems not related to impaired renal function or other comorbidities.