Development and independent validation of a prognostic gene expression signature based on RB1, PTEN, and TP53 in metastatic hormone-sensitive prostate cancer patients

Background: Androgen deprivation therapy (ADT) with docetaxel (D) and/or antiandrogen receptor therapies (ARTs) are the standard therapies in metastatic hormone-sensitive prostate cancer (mHSPC). Alterations in the tumor suppressor genes (TSGs) RB1, PTEN, and TP53 are associated with an aggressive e...

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Autores: Jiménez, Natalia, Rodriguez-Vida, Alejo, Mellado, Begoña
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/61397
Acceso en línea:http://hdl.handle.net/10230/61397
http://dx.doi.org/10.1016/j.euo.2023.12.012
Access Level:acceso abierto
Palabra clave:Androgen deprivation therapy
Biomarkers
CHAARTED trial
Docetaxel
Hormone-sensitive prostate cancer
Tumor suppressor genes
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spelling Development and independent validation of a prognostic gene expression signature based on RB1, PTEN, and TP53 in metastatic hormone-sensitive prostate cancer patientsJiménez, NataliaRodriguez-Vida, AlejoMellado, BegoñaAndrogen deprivation therapyBiomarkersCHAARTED trialDocetaxelHormone-sensitive prostate cancerTumor suppressor genesBackground: Androgen deprivation therapy (ADT) with docetaxel (D) and/or antiandrogen receptor therapies (ARTs) are the standard therapies in metastatic hormone-sensitive prostate cancer (mHSPC). Alterations in the tumor suppressor genes (TSGs) RB1, PTEN, and TP53 are associated with an aggressive evolution and treatment resistance in castration-resistant prostate cancer (CRPC). Objective: To study the clinical implications of TSG mRNA expression in mHSPC patients. Design, setting, and participants: This is a multicenter retrospective biomarker study in mHSPC patients. TSGlow status was defined when two or more out of the three TSGs presented low RNA expression by nCounter in formalin-fixed paraffin-embedded samples and TSGwt for the remaining cases. The microarray data from the CHAARTED trial were analyzed as an independent validation cohort. Outcome measurements and statistical analysis: Molecular data were correlated with CRPC-free survival (CRPC-FS) and overall survival (OS) by the Kaplan-Meier method and multivariate Cox analysis. Results and limitations: A total of 226 patients were included, of whom 218 were eligible: 93 were treated with ADT and 125 with ADT + D; 75.7% presented de novo stage IV and 67.9% high-volume disease. TSGlow (19.2%) was independently correlated with shorter CRPC-FS (hazard ratio [HR] 1.8, p = 0.002) and OS (HR 2, p = 0.002). In the CHAARTED trial, TSGlow was independently correlated with lower CRPC-FS (HR 2.2, p = 0.02); no differences in clinical outcomes according to treatment were observed in TSGlow patients, while a significant benefit was observed for ADT + D in the TSGwt group for CRPC-FS (HR 0.4, p < 0.001) and OS (HR 0.4, p = 0.001). However, no interaction was observed between TSG signature and treatment in either series. Study limitations are the retrospective design, small sample size, and lack of inclusion of patients treated with ADT + ART. Conclusions: TSGlow expression correlates with adverse outcomes in patients with mHSPC. The investigation of new therapeutic strategies in these patients is warranted. Patient summary: The low RNA expression of tumor suppressor genes in the tumors is correlated with adverse outcomes in patients with metastatic hormone-sensitive prostate cancer.Elsevier202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/61397http://dx.doi.org/10.1016/j.euo.2023.12.012reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésEur Urol Oncol. 2024 Aug;7(4):954-64© 2024 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/613972026-05-29T05:05:01Z
dc.title.none.fl_str_mv Development and independent validation of a prognostic gene expression signature based on RB1, PTEN, and TP53 in metastatic hormone-sensitive prostate cancer patients
title Development and independent validation of a prognostic gene expression signature based on RB1, PTEN, and TP53 in metastatic hormone-sensitive prostate cancer patients
spellingShingle Development and independent validation of a prognostic gene expression signature based on RB1, PTEN, and TP53 in metastatic hormone-sensitive prostate cancer patients
Jiménez, Natalia
Androgen deprivation therapy
Biomarkers
CHAARTED trial
Docetaxel
Hormone-sensitive prostate cancer
Tumor suppressor genes
title_short Development and independent validation of a prognostic gene expression signature based on RB1, PTEN, and TP53 in metastatic hormone-sensitive prostate cancer patients
title_full Development and independent validation of a prognostic gene expression signature based on RB1, PTEN, and TP53 in metastatic hormone-sensitive prostate cancer patients
title_fullStr Development and independent validation of a prognostic gene expression signature based on RB1, PTEN, and TP53 in metastatic hormone-sensitive prostate cancer patients
title_full_unstemmed Development and independent validation of a prognostic gene expression signature based on RB1, PTEN, and TP53 in metastatic hormone-sensitive prostate cancer patients
title_sort Development and independent validation of a prognostic gene expression signature based on RB1, PTEN, and TP53 in metastatic hormone-sensitive prostate cancer patients
dc.creator.none.fl_str_mv Jiménez, Natalia
Rodriguez-Vida, Alejo
Mellado, Begoña
author Jiménez, Natalia
author_facet Jiménez, Natalia
Rodriguez-Vida, Alejo
Mellado, Begoña
author_role author
author2 Rodriguez-Vida, Alejo
Mellado, Begoña
author2_role author
author
dc.subject.none.fl_str_mv Androgen deprivation therapy
Biomarkers
CHAARTED trial
Docetaxel
Hormone-sensitive prostate cancer
Tumor suppressor genes
topic Androgen deprivation therapy
Biomarkers
CHAARTED trial
Docetaxel
Hormone-sensitive prostate cancer
Tumor suppressor genes
description Background: Androgen deprivation therapy (ADT) with docetaxel (D) and/or antiandrogen receptor therapies (ARTs) are the standard therapies in metastatic hormone-sensitive prostate cancer (mHSPC). Alterations in the tumor suppressor genes (TSGs) RB1, PTEN, and TP53 are associated with an aggressive evolution and treatment resistance in castration-resistant prostate cancer (CRPC). Objective: To study the clinical implications of TSG mRNA expression in mHSPC patients. Design, setting, and participants: This is a multicenter retrospective biomarker study in mHSPC patients. TSGlow status was defined when two or more out of the three TSGs presented low RNA expression by nCounter in formalin-fixed paraffin-embedded samples and TSGwt for the remaining cases. The microarray data from the CHAARTED trial were analyzed as an independent validation cohort. Outcome measurements and statistical analysis: Molecular data were correlated with CRPC-free survival (CRPC-FS) and overall survival (OS) by the Kaplan-Meier method and multivariate Cox analysis. Results and limitations: A total of 226 patients were included, of whom 218 were eligible: 93 were treated with ADT and 125 with ADT + D; 75.7% presented de novo stage IV and 67.9% high-volume disease. TSGlow (19.2%) was independently correlated with shorter CRPC-FS (hazard ratio [HR] 1.8, p = 0.002) and OS (HR 2, p = 0.002). In the CHAARTED trial, TSGlow was independently correlated with lower CRPC-FS (HR 2.2, p = 0.02); no differences in clinical outcomes according to treatment were observed in TSGlow patients, while a significant benefit was observed for ADT + D in the TSGwt group for CRPC-FS (HR 0.4, p < 0.001) and OS (HR 0.4, p = 0.001). However, no interaction was observed between TSG signature and treatment in either series. Study limitations are the retrospective design, small sample size, and lack of inclusion of patients treated with ADT + ART. Conclusions: TSGlow expression correlates with adverse outcomes in patients with mHSPC. The investigation of new therapeutic strategies in these patients is warranted. Patient summary: The low RNA expression of tumor suppressor genes in the tumors is correlated with adverse outcomes in patients with metastatic hormone-sensitive prostate cancer.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/61397
http://dx.doi.org/10.1016/j.euo.2023.12.012
url http://hdl.handle.net/10230/61397
http://dx.doi.org/10.1016/j.euo.2023.12.012
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Eur Urol Oncol. 2024 Aug;7(4):954-64
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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