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 hormonesensitive prostate cancer (mHSPC). Alterations in the tumor suppressor genes (TSGs) RB1 , PTEN , and TP53 are associated with an aggressive...

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Autores: Jiménez, N, de Herreros, MG, Reig, O, Marin-Aguilera, M, Aversa, C, Ferrer-Mileo, L, Garcia-Esteve, S, Rodríguez-Carunchio, L, Trias, I, Font, A, Rodríguez-Vida, A, Climent, MA, Cros, S, Chirivella, I, Domènech, M, Figols, M, Carles, J, Suarez, C, Rivera, DH, González-Billalabeitia, E, Cívico, C, Sala-González, N, de Porras, VR, Ribal, MJ, Prat, A, Mellado, B
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p19149
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/19149
Access Level:acceso abierto
Palabra clave:Hormone-sensitive prostate cancer
Tumor suppressor genes
Biomarkers
Androgen deprivation therapy
Docetaxel
CHAARTED trial
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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, Nde Herreros, MGReig, OMarin-Aguilera, MAversa, CFerrer-Mileo, LGarcia-Esteve, SRodríguez-Carunchio, LTrias, IFont, ARodríguez-Vida, ACliment, MACros, SChirivella, IDomènech, MFigols, MCarles, JSuarez, CRivera, DHGonzález-Billalabeitia, ECívico, CSala-González, Nde Porras, VRRibal, MJPrat, AMellado, BHormone-sensitive prostate cancerTumor suppressor genesBiomarkersAndrogen deprivation therapyDocetaxelCHAARTED trialBackground: Androgen deprivation therapy (ADT) with docetaxel (D) and/or antiandrogen receptor therapies (ARTs) are the standard therapies in metastatic hormonesensitive 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. TSG low 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 TSG(wt )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. TSG(low )(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, TSG low was independently correlated with lower CRPC-FS (HR 2.2, p = 0.02); no differences in clinical outcomes according to treatment were observed in TSG(low )patients, while a significant benefit was observed for ADT + D in the TSG(wt )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: TSG(low )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. (c) 2024 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.ELSEVIER2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/19149European Urology OncologyISSN: 25889311reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p191492026-06-07T16:35:31Z
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, N
Hormone-sensitive prostate cancer
Tumor suppressor genes
Biomarkers
Androgen deprivation therapy
Docetaxel
CHAARTED trial
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, N
de Herreros, MG
Reig, O
Marin-Aguilera, M
Aversa, C
Ferrer-Mileo, L
Garcia-Esteve, S
Rodríguez-Carunchio, L
Trias, I
Font, A
Rodríguez-Vida, A
Climent, MA
Cros, S
Chirivella, I
Domènech, M
Figols, M
Carles, J
Suarez, C
Rivera, DH
González-Billalabeitia, E
Cívico, C
Sala-González, N
de Porras, VR
Ribal, MJ
Prat, A
Mellado, B
author Jiménez, N
author_facet Jiménez, N
de Herreros, MG
Reig, O
Marin-Aguilera, M
Aversa, C
Ferrer-Mileo, L
Garcia-Esteve, S
Rodríguez-Carunchio, L
Trias, I
Font, A
Rodríguez-Vida, A
Climent, MA
Cros, S
Chirivella, I
Domènech, M
Figols, M
Carles, J
Suarez, C
Rivera, DH
González-Billalabeitia, E
Cívico, C
Sala-González, N
de Porras, VR
Ribal, MJ
Prat, A
Mellado, B
author_role author
author2 de Herreros, MG
Reig, O
Marin-Aguilera, M
Aversa, C
Ferrer-Mileo, L
Garcia-Esteve, S
Rodríguez-Carunchio, L
Trias, I
Font, A
Rodríguez-Vida, A
Climent, MA
Cros, S
Chirivella, I
Domènech, M
Figols, M
Carles, J
Suarez, C
Rivera, DH
González-Billalabeitia, E
Cívico, C
Sala-González, N
de Porras, VR
Ribal, MJ
Prat, A
Mellado, B
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hormone-sensitive prostate cancer
Tumor suppressor genes
Biomarkers
Androgen deprivation therapy
Docetaxel
CHAARTED trial
topic Hormone-sensitive prostate cancer
Tumor suppressor genes
Biomarkers
Androgen deprivation therapy
Docetaxel
CHAARTED trial
description Background: Androgen deprivation therapy (ADT) with docetaxel (D) and/or antiandrogen receptor therapies (ARTs) are the standard therapies in metastatic hormonesensitive 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. TSG low 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 TSG(wt )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. TSG(low )(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, TSG low was independently correlated with lower CRPC-FS (HR 2.2, p = 0.02); no differences in clinical outcomes according to treatment were observed in TSG(low )patients, while a significant benefit was observed for ADT + D in the TSG(wt )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: TSG(low )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. (c) 2024 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.
publishDate 2024
dc.date.none.fl_str_mv 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 https://incliva.portalinvestigacion.com/publicaciones/19149
url https://incliva.portalinvestigacion.com/publicaciones/19149
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ELSEVIER
publisher.none.fl_str_mv ELSEVIER
dc.source.none.fl_str_mv European Urology Oncology
ISSN: 25889311
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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