Androgen receptor and its splicing variant 7 expression in peripheral blood mononuclear cells and in circulating tumor cells in metastatic castration-resistant prostate cancer

Marín Aguilera, MercedesJiménez, NataliaReig Torras, OscarMontalbo Calafell, RuthVerma, Ajit K.Castellano, GiancarloMengual Brichs, LourdesVictoria, IvánPereira, María VerónicaMilà Guasch, MariaGarcía-Recio, SusanaBenítez-Ribas, DanielCabezón, RaquelGonzález, AzucenaJuan, ManelPrat Aparicio, AleixMellado González, Begoña2021-03-222021-03-222020-01-142073-4409https://hdl.handle.net/2445/175547Androgen receptor (AR) signaling remains crucial in castration-resistant prostate cancer (CRPC). Since it is also essential in immune cells, we studied whether the expression of AR full-length (ARFL) and its splicing variant ARV7 in peripheral blood mononuclear cells (PBMC) predicts systemic treatment response in mCRPC in comparison with circulating-tumor cells (CTC). We measured ARFL and ARV7 mRNA in PBMC and CTC from patients prior to receiving abiraterone (AA), enzalutamide (E), or taxanes by a pre-amplification plus quantitative reverse-transcription PCR. They were also tested in LNCaP-ARV7-transfected and in 22RV1 docetaxel-resistant (22RV1DR) cells. We studied 171 PBMC from 136 patients and from 24 non-cancer controls, and 47 CTC from 22 patients. High PBMC ARV7 levels correlated with worse AA/E and better taxane response. In taxane-treated patients high PBMC ARFL also correlated with longer progression-free survival (PFS). High ARV7 and ARFL expression were independently associated with better biochemical-PFS. Conversely, high CTC ARV7 and ARFL correlated with shorter radiological-PFS and overall survival, respectively. High ARV7 in 22RV1DR and LNCaP-ARV7 cells correlated with taxane resistance. In conclusion, ARFL and ARV7 at PBMC or CTC have a different predictive role in the taxane response, suggesting a potential influence of the AR pathway from PBMC in such response modulation.19 p.application/pdfengcc-by (c) Marín Aguilera, Mercedes et al., 2020http://creativecommons.org/licenses/by/3.0/esCàncer de pròstataAndrògensProstate cancerAndrogensAndrogen receptor and its splicing variant 7 expression in peripheral blood mononuclear cells and in circulating tumor cells in metastatic castration-resistant prostate cancerinfo:eu-repo/semantics/article7017142021-03-22info:eu-repo/semantics/openAccess31947623