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Title: | Androgen receptor and its splicing variant 7 expression in peripheral blood mononuclear cells and in circulating tumor cells in metastatic castration-resistant prostate cancer |
Author: | Marín Aguilera, Mercedes Jiménez, Natalia Reig Torras, Oscar Montalbo Calafell, Ruth Verma, Ajit K. Castellano, Giancarlo Mengual Brichs, Lourdes Victoria, Iván Pereira, María V. Milà Guasch, Maria García-Recio, Susana Benítez-Ribas, Daniel Cabezón, Raquel González, Azucena Juan, Manel Prat Aparicio, Aleix Mellado González, Begoña |
Keywords: | Càncer de pròstata Andrògens Prostate cancer Androgens |
Issue Date: | 14-Jan-2020 |
Publisher: | MDPI |
Abstract: | Androgen 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/cells9010203 |
It is part of: | Cells, 2020, vol. 9, num. 1, p. 203 |
URI: | http://hdl.handle.net/2445/175547 |
Related resource: | https://doi.org/10.3390/cells9010203 |
ISSN: | 2073-4409 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Biomedicina) |
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