Expression pattern of androgen receptor (AR), splice variant 7 (AR-V7) and splice variant 567 (AR-567) in circulating tumor cells and paired plasma-derived exosomes in metastatic castration resistant prostate cancer

INTRODUCTION: Androgen-receptor splice variant 7 (AR-V7)is a highly promising liquid biopsy predictive biomarker indicating primary or acquired resistance to novel androgen receptor signaling inhibitors in metastatic castration resistant prostate cancer (mCRPC). We present for the first time the expression pattern of AR-FL, AR-V7, and AR-567es at a quantitative level in circulating tumor cells (CTCs) and paired plasma-derived exosomes in mCRPC. METHODS: We first developed and analytically validated a novel multiplex RT-qPCR assay for AR full length (AR-FL), AR-V7, AR-567es and AR-total. We then quantified the expression levels of AR-splice variants, CK-19 (epithelial marker) and B2M (reference gene) in EpCAM+ CTCs and paired plasma-derived exosomes isolated from peripheral blood (20mL) of 62 mCRPC patients and 10 healthy donors. RESULTS: In CTCs AR-FL was detected in 57/62(92%),AR-V7 in 32/62(52.0%),AR-567es in15/62(24.2%) and AR-total in 56/62(90.0%). In paired plasma-derived exosomes, AR-FL was detected in 45/62(72.5%), AR-V7 in 4/62(6.5%), AR-567 in 2/62(3.2%) and AR total in 47/62(75.8%).CK-19 expression was detected in 18/62(29.0%) of CTCs and in 28/62(45.2%) of exosomes. In all cases AR splice variants were expressed at higher levels in CTCs than in paired exosomes, while AR-V7 was detected at higher percentages than AR-567es. CONCLUSIONS: Our results reveal for the first time a remarkable heterogeneity on the expression levels of AR-FL, AR-V7 and AR-567es in EpCAM+ CTCs and paired exosomes between individual mCRPC patients. The clinical significance of this finding will be further investigated in large patient cohorts in respect to therapy response. Citation Format: Areti D. Strati, Martha Zavridou, Evangelos Bournakis, Sophia Mastoraki, Evi S. Lianidou. Expression pattern of androgen receptor (AR), splice variant 7 (AR-V7) and splice variant 567 (AR-567) in circulating tumor cells and paired plasma-derived exosomes in metastatic castration resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2290.