Department of Urology, Semmelweis University, Budapest, Hungary; Department of Urology, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
Department of Urology, Semmelweis University, Budapest, Hungary.
Urol Oncol. 2021 May;39(5):296.e11-296.e19. doi: 10.1016/j.urolonc.2020.09.005. Epub 2020 Oct 9.
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.
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.
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.
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.
转移性去势抵抗性前列腺癌（mCRPC）的治疗领域迅速变化，需要生物标志物来指导治疗决策。我们最近发现 MMP-7 可作为预测接受多西他赛（DOC）化疗的 mCRPC 患者反应和生存的潜在血清标志物。在此，我们旨在在独立患者队列中检验这一发现，并探讨血清 MMP-7 在阿比特龙（ABI）或恩扎鲁胺（ENZA）治疗患者中的预后潜力。
使用 ELISA 法测量了 320 名 mCRPC 患者的 836 份血清样本中的 MMP-7 水平，这些患者在接受 DOC（n=95）、ABI（n=140）或 ENZA（n=85）治疗前和治疗期间采集了这些样本。结果与临床和随访数据相关联。
3 种治疗组的 MMP-7 基线水平相似。在 ABI 和 ENZA 队列中，有根治性前列腺切除术史的患者基线 MMP-7 水平较低（P=0.058 和 P=0.041）。DOC（P=0.001）和 ENZA（P=0.006）队列中，基线 MMP-7 水平高于中位数与总生存期较短相关。DOC 和 ENZA 队列的多变量分析显示，高预处理 MMP-7 水平是患者生存的独立危险因素。此外，在基线 MMP-7 水平较高的接受 DOC 治疗的患者中，第 3 个 DOC 周期时标志物下降与生存改善相关。与接受 DOC 或 ENZA 治疗相比，基线 MMP-7 水平较高的患者接受 ABI 治疗的生存情况更好。
我们证实了预处理 MMP-7 血清水平及其变化作为接受 DOC 治疗的 mCRPC 患者生存的独立预测因子的预后价值。此外，高 MMP-7 是接受 ENZA 治疗但不是接受 ABI 治疗患者的负预测因子。这些结果需要进一步研究来证实血清 MMP-7 的预测价值，并探讨 MMP-7 在 mCRPC 患者对 DOC 和 ENZA 耐药性中的潜在机制作用。
