Androgen Receptor and Its Splicing Variant 7 Expression in Peripheral Blood Mononuclear Cells and in Circulating Tumor Cells in Metastatic Castration-Resistant Prostate Cancer

oleh: Mercedes Marín-Aguilera, Natalia Jiménez, Òscar Reig, Ruth Montalbo, Ajit K. Verma, Giancarlo Castellano, Lourdes Mengual, Iván Victoria, María V. Pereira, Maria Milà-Guasch, Susana García-Recio, Daniel Benítez-Ribas, Raquel Cabezón, Azucena González, Manel Juan, Aleix Prat, Begoña Mellado

Format: Article
Diterbitkan: MDPI AG 2020-01-01

Deskripsi

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 <i>(ARFL)</i> and its splicing variant <i>ARV7</i> in peripheral blood mononuclear cells (PBMC) predicts systemic treatment response in mCRPC in comparison with circulating-tumor cells (CTC). We measured <i>ARFL</i> and <i>ARV7</i> 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-<i>ARV7</i>-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 <i>ARV7</i> levels correlated with worse AA/E and better taxane response. In taxane-treated patients high PBMC <i>ARFL</i> also correlated with longer progression-free survival (PFS). High <i>ARV7</i> and <i>ARFL</i> expression were independently associated with better biochemical-PFS. Conversely, high CTC <i>ARV7</i> and <i>ARFL</i> correlated with shorter radiological-PFS and overall survival, respectively. High <i>ARV7</i> in 22RV1DR and LNCaP-<i>ARV7</i> cells correlated with taxane resistance. In conclusion, <i>ARFL</i> and <i>ARV7</i> 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.