Prognostic Stratification of Metastatic Prostate Cancer Patients Treated With Abiraterone and Enzalutamide Through an Integrated Analysis of Circulating Free microRNAs and Clinical Parameters

Abstract

Androgen Receptor-Targeted Agents (ARTA) have dramatically changed the therapeutic landscape of metastatic Castration-Resistant Prostate Cancer (mCRPC), but 20–40% of these patients progress early after start of ARTA treatment. The present study investigated the potential utility of plasma cell-free microRNAs (cfmiRNAs) as prognostic markers by analyzing a prospective cohort of 31 mCRCP patients treated with abiraterone (N = 10) or enzalutamide (N = 21). Additional potential prognostic factors were extracted from clinical records and outcome was evaluated as overall survival (OS) and progression-free survival (PFS). cfmiRNAs were measured in plasma samples using quantitative real-time RT-PCR. Linear correlation among clinical factors and cfmiRNAs was assessed using the Spearman's rank correlation coefficient. The association with survival was studied using univariate and multivariate Cox proportional hazards models. Continuous variables were dichotomized with the cut points corresponding to the most significant relation with the outcome. Univariate analysis indicated that plasma levels of miR-21-5p, miR-141-3p and miR-223-3p, time to development of castration-resistance (tCRPC), and blood hemoglobin (Hb) levels strongly correlated with both PFS and OS. Multivariate analysis revealed that low plasma levels of miR-21, shorter tCRPC, and lower Hb values were independent factors predicting reduced PFS and OS. These findings suggest that the integrated analysis of cfmiRNAs, tCRPC, and Hb may provide a promising, non-invasive tool for the prognostic stratification of mCRPC patients treated with ARTA.

Prognostic value of miR-21 for prostate cancer: a systematic review and meta-analysis

“…Amankwah, 2013 [ 31 ] indicated that the recurrent group was oversampled, no rationale was provided. Sharova, 2021 [ 78 ] was clearly indicated as prospective; Zedan, 2017 [ 85 ] and Zhao, 2019a [ 89 ] were clearly indicated as retrospective studies. Cohort types were projected for the rest judging by the details contained.…”

“…The remaining 63 studies [79][80][81][82][83][84][85][86][87][88][89][90][91][92] were included in the systematic review, with 10 eligible for meta-analysis. On 8 th November 2021, an update screening for meta-analysis identified one more eligible study 78 , bringing the total number of included studies to 64, with 11 eligible for meta-analysis.…”

“…Eleven eligible studies were allocated into four separate meta-analyses according to outcomes and handlings of miR-21 data. Note: Sharova202178 with two outcomes was allocated into Analyses 3 and 4. OS: Overall survival; PFS: Progression-free survival; RFS: Recurrence-free survival Downloaded from http://portlandpress.com/bioscirep/article-pdf/doi/10.1042/BSR20211972/926844/bsr-2021-1972.pdf by guest on 27 December 2021…”

The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

“…A recent study of a small cohort of patients with metastatic PC was focused on identifying plasma miRNAs and other parameters associated with development of resistance to the androgen antagonists abiraterone and enzalutamide [ 189 ]. Univariate analysis identified an association between plasma levels of miR-141 (high), miR-21-5p (low) and miR-223-3p (low), time to development of castration resistance (tCRPC) and low blood hemoglobin (Hb) levels with poor PFS and OS.…”

“…Univariate analysis identified an association between plasma levels of miR-141 (high), miR-21-5p (low) and miR-223-3p (low), time to development of castration resistance (tCRPC) and low blood hemoglobin (Hb) levels with poor PFS and OS. miR-141 and miR-223-3p dropped out upon multivariate analysis, which indicated miR-21, Hb and tCRPC as independent factors predicting OS, and miR-21 and tCRPC predicting PFS [ 189 ].…”