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RESEARCH PRODUCT
The Detection of Androgen Receptor Splice Variant 7 in Plasma-derived Exosomal RNA Strongly Predicts Resistance to Hormonal Therapy in Metastatic Prostate Cancer Patients
Stefania CrucittaEleonora RofiRomano DanesiLisa DerosaRon H.n. Van SchaikMarzia Del ReMario MiccoliElisa BiascoCinzia OrlandiniAlfredo FalconeG. JensterLuca Gallisubject
Oncology0301 basic medicineMaleResistanceExosomeschemistry.chemical_compoundProstate cancer0302 clinical medicineProtein IsoformsNeoplasm MetastasisReceptorAged 80 and overProstate cancerMiddle AgedProstatic Neoplasms Castration-ResistantReceptors Androgen030220 oncology & carcinogenesisBenzamidesAdenocarcinomaBiomarker (medicine)Hormonal therapyAR-V7; Digital droplet PCR; Exosomes; Hormonal therapy; Pharmacogenetics; Prostate cancer; Resistance; UrologyAndrostenesHormonal therapymedicine.medical_specialtyAntineoplastic Agents Hormonalmedicine.drug_classUrologyCastration resistantAdenocarcinomaDisease-Free Survival03 medical and health sciencesSDG 3 - Good Health and Well-beingInternal medicineNitrilesPhenylthiohydantoinmedicineEnzalutamideHumansAgedDigital droplet PCRPlasma derivedbusiness.industryRNAAndrogen Receptor Splice Variant 7medicine.diseaseAndrogenEndocrinology030104 developmental biologychemistryPharmacogeneticsDrug Resistance NeoplasmCancer cellCancer researchRNAAR-V7businessPharmacogeneticsdescription
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 + participants at baseline compared with AR-V7 − participants (8 mo vs not reached; p 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-01-01 |