Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel.

(1) Background: Androgen deprivation therapy (ADT) and docetaxel (DX) combination is a standard therapy for metastatic hormone-sensitive prostate cancer (mHSPC) patients. (2) Methods: We investigate if tumor transcriptomic analysis predicts mHSPC evolution in a multicenter retrospective biomarker study. A customized panel of 184 genes was tested in mRNA from tumor samples by the nCounter platform in 125 mHSPC patients treated with ADT+DX. Gene expression was correlated with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). (3) Results: High expression of androgen receptor (AR) signature was independently associated with longer CRPC-FS (hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.3-0.9; p = 0.015), high expression of estrogen receptor (ESR) signature with longer CRPC-FS (HR 0.6, 95% CI 0.4-0.9; p = 0.019) and OS (HR 0.5, 95% CI 0.2-0.9, p = 0.024), and lower expression of tumor suppressor genes (TSG) (RB1, PTEN and TP53) with shorter OS (HR 2, 95% CI 1-3.8; p = 0.044). ARV7 expression was independently associated with shorter CRPC-FS (HR 1.5, 95% CI 1.1-2.1, p = 0.008) and OS (HR 1.8, 95% CI 1.2-2.6, p = 0.004), high ESR2 was associated with longer OS (HR 0.5, 95% CI 0.2-1, p = 0.048) and low expression of RB1 was independently associated with shorter OS (HR 1.9, 95% CI 1.1-3.2, p = 0.014). (4) Conclusions: AR, ESR, and TSG expression signatures, as well as ARV7, RB1, and ESR2 expression, have a prognostic value in mHSPC patients treated with ADT+DX.

Cancers. 2022 Sep 29*** epublish ***

Natalia Jiménez, Òscar Reig, Mercedes Marín-Aguilera, Caterina Aversa, Laura Ferrer-Mileo, Albert Font, Alejo Rodriguez-Vida, Miguel Ángel Climent, Sara Cros, Isabel Chirivella, Montserrat Domenech, Mariona Figols, Enrique González-Billalabeitia, Daniel Jiménez Peralta, Leonardo Rodríguez-Carunchio, Samuel García-Esteve, Marta Garcia de Herreros, Maria J Ribal, Aleix Prat, Begoña Mellado

Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain., Medical Oncology Department, Institut Català d'Oncologia, Hospital Germans Trias i Pujol, 08916 Badalona, Spain., Medical Oncology Department, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Hospital del Mar, 08003 Barcelona, Spain., Medical Oncology Service, Instituto Valenciano de Oncología (IVO), 46009 Valencia, Spain., Medical Oncology Department, Hospital General de Granollers, 08402 Granollers, Spain., Oncology Department, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain., Medical Oncology Department, Fundació Althaia Manresa, 08243 Manresa, Spain., Medical Oncology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain., Urology Department, Hospital General Universitario José M. Morales Meseguer, 30008 Murcia, Spain., Uro-Oncology Unit, Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain., Medical Oncology Department, Hospital Clínic, 08036 Barcelona, Spain.

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