Format

Send to

Choose Destination
Eur Urol. 2017 Apr;71(4):680-687. doi: 10.1016/j.eururo.2016.08.012. Epub 2016 Oct 10.

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

Author information

1
Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. Electronic address: marzia.delre@gmail.com.
2
Medical Oncology Unit, Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy.
3
Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
4
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
5
Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
6
Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.

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.

KEYWORDS:

AR-V7; Digital droplet PCR; Exosomes; Hormonal therapy; Pharmacogenetics; Prostate cancer; Resistance

PMID:
27733296
DOI:
10.1016/j.eururo.2016.08.012
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center