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

Autor:	Marín-Aguilera M; Translational Genomics Group and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.; Fundació Clínic per a la Recerca Biomèdica, 08036 Barcelona, Spain., Jiménez N; Translational Genomics Group and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.; Fundació Clínic per a la Recerca Biomèdica, 08036 Barcelona, Spain., Reig Ò; Translational Genomics Group and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.; Fundació Clínic per a la Recerca Biomèdica, 08036 Barcelona, Spain.; Medical Oncology Department, Hospital Clínic, 08036 Barcelona, Spain., Montalbo R; Translational Genomics Group and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.; Fundació Clínic per a la Recerca Biomèdica, 08036 Barcelona, Spain., Verma AK; Department of Human Oncology, University of Wisconsin-Madison, Madison, WI 53706, USA., Castellano G; Genomic Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain., Mengual L; Department and Laboratory of Urology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centre de Recerca Biomèdica CELLEX, 08036 Barcelona, Spain.; Department of Biomedicine, University of Barcelona, 08007 Barcelona, Spain., Victoria I; Fundació Clínic per a la Recerca Biomèdica, 08036 Barcelona, Spain.; Medical Oncology Department, Hospital Clínic, 08036 Barcelona, Spain., Pereira MV; Fundació Clínic per a la Recerca Biomèdica, 08036 Barcelona, Spain.; Medical Oncology Department, Hospital Clínic, 08036 Barcelona, Spain., Milà-Guasch M; Translational Genomics Group and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain., García-Recio S; Translational Genomics Group and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.; Fundació Clínic per a la Recerca Biomèdica, 08036 Barcelona, Spain., Benítez-Ribas D; Immunology Department, Hospital Clínic, 08036 Barcelona, Spain., Cabezón R; Immunology Department, Hospital Clínic, 08036 Barcelona, Spain., González A; Immunology Department, Hospital Clínic, 08036 Barcelona, Spain., Juan M; Immunology Department, Hospital Clínic, 08036 Barcelona, Spain., Prat A; Translational Genomics Group and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.; Medical Oncology Department, Hospital Clínic, 08036 Barcelona, Spain.; Department of Medicine, University of Barcelona, 08036 Barcelona, Spain., Mellado B; Translational Genomics Group and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.; Medical Oncology Department, Hospital Clínic, 08036 Barcelona, Spain.; Department of Medicine, University of Barcelona, 08036 Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	Cells [Cells] 2020 Jan 14; Vol. 9 (1). Date of Electronic Publication: 2020 Jan 14.
DOI:	10.3390/cells9010203
Abstrakt:	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. Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu