Urine-based liquid biopsy: non-invasive and sensitive AR-V7 detection in urinary EVs from patients with prostate cancer.

Androgen-receptor splice variant 7 (AR-V7) is associated with castration-resistant prostate cancer (CRPC) and resistance to anti-androgen therapy. Despite its clinical importance, the lack of efficient methods for AR-V7 analysis remains a challenge for broader use of this biomarker in routine clinical practice.

Herein, we suggest a practical and non-invasive liquid biopsy method for analysis of AR-V7 in the RNA of urine-derived extracellular vesicles (EVs) without the need for blood withdrawal. Urine-derived EVs were isolated by a lab-on-a-disc integrated with six independent nanofiltration units (Exo-Hexa) allowing simultaneous processing of six individual samples. Rapid enrichment of EVs (<30 min) from each 4 mL urine sample was followed by mRNA extraction, and AR-V7 and androgen receptor full-length (AR-FL) mRNA levels in the urinary EVs were quantified by droplet digital polymerase chain reaction (ddPCR) as absolute concentrations (copies per mL). Higher AR-V7 and lower AR-FL expressions were detected in urine-derived EVs from 14 patients with CRPC than in those from 22 patients with hormone-sensitive prostate cancer. Additionally, we found that AR-V7 transcript levels and the AR-V7/AR-FL ratio in urinary EVs were higher in patients with advanced prostate cancer. This study is the first to report that RNA of urine-derived EVs is a reliable source for AR-V7 expression analysis. The proposed method for quantifying AR-V7 in urinary EVs prepared by a lab-on-a-disc is therefore a simple and promising approach to liquid biopsy with great potential for therapeutic impact on prostate cancer.

Lab on a chip. 2018 Nov 30 [Epub ahead of print]

Hyun-Kyung Woo, Juhee Park, Ja Yoon Ku, Chan Ho Lee, Vijaya Sunkara, Hong Koo Ha, Yoon-Kyoung Cho

Department of Biomedical Engineering, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea. and Center for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea., Center for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea., Department of Urology, Pusan National University Hospital, Pusan National University School of Medicine, Busan 49241, Republic of Korea. ., Department of Urology, Inje University Busan Paik Hospital, Busan 47392, Republic of Korea.