Prognostic Expression Signature of RB1 , PTEN , and TP53 Genes in Patients with Metastatic Hormone-sensitive Prostate Cancer Treated with Androgen Receptor Pathway Inhibitors.

Autor:	Garcia de Herreros M; Translational Genomics and Targeted Therapeutics in Solid Tumours Lab, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.; Medical Oncology Department, Hospital Clínic, Barcelona, Spain.; Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain., Jiménez N; Translational Genomics and Targeted Therapeutics in Solid Tumours Lab, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain., Rodríguez-Carunchio L; Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain.; Department of Pathology, Hospital Clínic, Barcelona, Spain., Lillo E; Medical Oncology Department, Hospital Clínic, Barcelona, Spain.; Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain., Marín-Aguilera M; Translational Genomics and Targeted Therapeutics in Solid Tumours Lab, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain., Ferrer-Mileo L; Translational Genomics and Targeted Therapeutics in Solid Tumours Lab, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.; Medical Oncology Department, Hospital Clínic, Barcelona, Spain.; Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain., Aversa C; Translational Genomics and Targeted Therapeutics in Solid Tumours Lab, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.; Medical Oncology Department, Hospital Clínic, Barcelona, Spain.; Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain., García-Esteve S; Translational Genomics and Targeted Therapeutics in Solid Tumours Lab, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.; Department of Medicine, University of Barcelona, Barcelona, Spain., Padrosa J; Translational Genomics and Targeted Therapeutics in Solid Tumours Lab, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.; Medical Oncology Department, Hospital Clínic, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain., Trias I; Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain.; Department of Pathology, Hospital Clínic, Barcelona, Spain., Fernández-Mañas L; Translational Genomics and Targeted Therapeutics in Solid Tumours Lab, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.; Medical Oncology Department, Hospital Clínic, Barcelona, Spain.; Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain., Font A; Medical Oncology Department, Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Badalona, Spain., Chirivella I; Department of Medical Oncology, Hospital Clínico Universitario de Valencia, Instituto de Investigación Sanitaria (INCLIVA), University of Valencia, Valencia, Spain., Figols M; Medical Oncology Department, Fundació Althaia, Xarxa Assistencial Universitària de Manresa, Manresa, Spain., Climent MÁ; Medical Oncology Service, Instituto Valenciano de Oncología (IVO), Valencia, Spain., Prat A; Translational Genomics and Targeted Therapeutics in Solid Tumours Lab, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.; Medical Oncology Department, Hospital Clínic, Barcelona, Spain.; Department of Medicine, University of Barcelona, Barcelona, Spain., Reig Ò; Translational Genomics and Targeted Therapeutics in Solid Tumours Lab, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.; Medical Oncology Department, Hospital Clínic, Barcelona, Spain.; Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain.; Department of Medicine, University of Barcelona, Barcelona, Spain., Mellado B; Translational Genomics and Targeted Therapeutics in Solid Tumours Lab, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.; Medical Oncology Department, Hospital Clínic, Barcelona, Spain.; Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain.; Department of Medicine, University of Barcelona, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	European urology open science [Eur Urol Open Sci] 2024 Oct 21; Vol. 70, pp. 86-90. Date of Electronic Publication: 2024 Oct 21 (Print Publication: 2024).
DOI:	10.1016/j.euros.2024.10.008
Abstrakt:	Alterations in the tumor suppressor genes (TSGs) RB1 , PTEN , and TP53 are associated with treatment resistance, worse survival, and aggressive variants of prostate cancer (AVPC). We previously developed and validated a signature reflecting low TSG expression (TSG low ) that was associated with poor outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT) ± docetaxel. The aim of this multicenter retrospective study was to validate the TSG low signature in patients with mHSPC treated with ADT and an androgen receptor pathway inhibitor (ARPI) and to explore clinical characteristics at progression according to TSG status. TSG mRNA expression in formalin-fixed, paraffin-embedded samples was assessed via nCounter. Correlation of expression levels with castration-resistant prostate cancer-free survival (CRPC-FS; primary endpoint) and overall survival (OS) was investigated via Kaplan-Meier and multivariate Cox analyses. Of the 137 patients included, 77.4% had de novo stage IV cancer and 44.5% had high-risk disease. TSG low (16.8%) was correlated with visceral metastases ( p  = 0.013), high-risk disease ( p  = 0.038), higher Gleason score ( p  = 0.026), shorter CRPC-FS (hazard ratio 1.9; p  = 0.046) and higher AVPC frequency ( p  = 0.01). Our results confirm that a TSG low signature is an adverse prognostic factor and is associated with AVPC development in patients with mHSPC treated with ADT + ARPI. Further prospective validation is needed to define specific therapeutic strategies for these patients. Patient Summary: We looked at outcomes for patients with metastatic hormone-sensitive prostate cancer treated with hormone therapies. We found that patients with low expression of two out of three tumor suppressor genes ( TP53 , RB1 , PTEN ) had worse clinical outcomes and had aggressive variants of prostate cancer. Measuring the expression of these genes in early-stage prostate cancer could help in finding better treatments for these patients. (© 2024 The Authors.)
Databáze:	MEDLINE
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