BACKGROUND: The androgen receptor splice variant 7 (AR-V7) is associated with resistance to hormonal therapy in castration-resistant prostate cancer (CRPC). Due to limitations of the methods available for AR-V7 analysis, the identification of a reliable detection method may facilitate the use of this biomarker in clinical practice. OBJECTIVE: To confirm AR-V7 as a predictor of resistance to hormonal therapy and develop a new approach to assess AR-V7 by highly sensitive digital droplet polymerase chain reaction (ddPCR) in plasma-derived exosomal RNA. DESIGN, SETTING, AND PARTICIPANTS: Plasma samples were collected from 36 CRPC patients before they began second-line hormonal treatment. Exosomes were isolated and RNA extracted for analysis of AR-V7 by ddPCR. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The absolute target gene concentration as copies per milliliter (copies/ml) was determined by ddPCR. Statistical analyses were performed with SPSS software (IBM Corp., Armonk, NY, USA). RESULTS AND LIMITATIONS: A total of 26 patients received abiraterone and 10 enzalutamide; 39% of patients were found to be AR-V7 positive (AR-V7+). Median progression-free survival was significantly longer in AR-V7 negative (AR-V7-) versus AR-V7+ patients (20 vs 3 mo; p<0.001). Overall survival was significantly shorter in AR-V7+ participants at baseline compared with AR-V7- participants (8 mo vs not reached; p<0.001). CONCLUSIONS: This study demonstrates that plasma-derived exosomal RNA is a reliable source of AR-V7 that can be detected sensitively by ddPCR assay. We also showed that resistance to hormonal therapy may be predicted by AR-V7, making it a clinically relevant biomarker. PATIENT SUMMARY: We report a first study on a method for androgen receptor splice variant 7 (AR-V7) detection in RNA extracted from cancer cell vesicles released in blood. Results confirmed the role of AR-V7 as a predictive biomarker of resistance to hormonal therapy. Our assay showed that vesicles are a reliable source of AR-V7 RNA and that the method is fast, highly sensitive, and affordable.

The Detection of Androgen Receptor Splice Variant 7 in Plasma-derived Exosomal RNA Strongly Predicts Resistance to Hormonal Therapy in Metastatic Prostate Cancer Patients

DEL RE, MARZIA;BIASCO, ELISA;CRUCITTA, STEFANIA;DEROSA, LISA;MICCOLI, MARIO;FALCONE, ALFREDO;DANESI, ROMANO
2017-01-01

Abstract

BACKGROUND: The androgen receptor splice variant 7 (AR-V7) is associated with resistance to hormonal therapy in castration-resistant prostate cancer (CRPC). Due to limitations of the methods available for AR-V7 analysis, the identification of a reliable detection method may facilitate the use of this biomarker in clinical practice. OBJECTIVE: To confirm AR-V7 as a predictor of resistance to hormonal therapy and develop a new approach to assess AR-V7 by highly sensitive digital droplet polymerase chain reaction (ddPCR) in plasma-derived exosomal RNA. DESIGN, SETTING, AND PARTICIPANTS: Plasma samples were collected from 36 CRPC patients before they began second-line hormonal treatment. Exosomes were isolated and RNA extracted for analysis of AR-V7 by ddPCR. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The absolute target gene concentration as copies per milliliter (copies/ml) was determined by ddPCR. Statistical analyses were performed with SPSS software (IBM Corp., Armonk, NY, USA). RESULTS AND LIMITATIONS: A total of 26 patients received abiraterone and 10 enzalutamide; 39% of patients were found to be AR-V7 positive (AR-V7+). Median progression-free survival was significantly longer in AR-V7 negative (AR-V7-) versus AR-V7+ patients (20 vs 3 mo; p<0.001). Overall survival was significantly shorter in AR-V7+ participants at baseline compared with AR-V7- participants (8 mo vs not reached; p<0.001). CONCLUSIONS: This study demonstrates that plasma-derived exosomal RNA is a reliable source of AR-V7 that can be detected sensitively by ddPCR assay. We also showed that resistance to hormonal therapy may be predicted by AR-V7, making it a clinically relevant biomarker. PATIENT SUMMARY: We report a first study on a method for androgen receptor splice variant 7 (AR-V7) detection in RNA extracted from cancer cell vesicles released in blood. Results confirmed the role of AR-V7 as a predictive biomarker of resistance to hormonal therapy. Our assay showed that vesicles are a reliable source of AR-V7 RNA and that the method is fast, highly sensitive, and affordable.
2017
DEL RE, Marzia; Biasco, Elisa; Crucitta, Stefania; Derosa, Lisa; Rofi, Eleonora; Orlandini, Cinzia; Miccoli, Mario; Galli, Luca; Falcone, Alfredo; Jen...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/826124
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