Clinical and Transcriptomic Characterization of Metastatic Hormone-Sensitive Prostate Cancer Patients with Low PTEN Expression

Alterations in the PTEN tumor suppressor gene are common in prostate cancer. They have been associated with a more aggressive disease and poor outcomes and potential benefit of targeted therapies. The purpose of this work is to study the clinical and transcriptional landscapes associated to low PTEN...

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Autores: Garcia de Herreros M, Jiménez N, Padrosa J, Aversa C, Ferrer-Mileo L, García-Esteve S, Rodríguez-Carunchio L, Trias I, Fernández-Mañas L, Marín-Aguilera M, Altamirano M, Mazariegos M, Font A, Rodriguez-Vida A, Climent MÁ, Cros S, Chirivella I, Figols M, Sala-González N, Ruiz de Porras V, Pardo JC, Prat A, Reig Ò, Mellado B
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p20200
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/20200
Access Level:acceso abierto
Palabra clave:hormone-sensitive prostate cancer
PTEN
biomarkers
androgen deprivation therapy
docetaxel
androgen receptor signaling inhibitors
CHAARTED trial
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spelling Clinical and Transcriptomic Characterization of Metastatic Hormone-Sensitive Prostate Cancer Patients with Low PTEN ExpressionGarcia de Herreros MJiménez NPadrosa JAversa CFerrer-Mileo LGarcía-Esteve SRodríguez-Carunchio LTrias IFernández-Mañas LMarín-Aguilera MAltamirano MMazariegos MFont ARodriguez-Vida ACliment MÁCros SChirivella IFigols MSala-González NRuiz de Porras VPardo JCPrat AReig ÒMellado Bhormone-sensitive prostate cancerPTENbiomarkersandrogen deprivation therapydocetaxelandrogen receptor signaling inhibitorsCHAARTED trialAlterations in the PTEN tumor suppressor gene are common in prostate cancer. They have been associated with a more aggressive disease and poor outcomes and potential benefit of targeted therapies. The purpose of this work is to study the clinical and transcriptional landscapes associated to low PTEN mRNA expression in metastatic hormone-sensitive prostate cancer (mHSPC) patients. A multicenter biomarker ambispective study was performed in mHSPC patients. PTEN mRNA expression was assessed by nCounter in formalin-fixed paraffin-embedded tumor samples. PTENlow status was defined by a previously validated cut-off and was correlated with castration-resistant prostate cancer (CRPC)-free survival (CRPC-FS) (primary endpoint) and overall survival (OS). RNA-Seq was performed to molecularly characterize PTENlow vs. PTENwt tumors. A total of 380 patients were included, 350 eligible. PTENlow was observed in 28.2% of patients and was independently associated with shorter CRPC-FS (HR 1.6, 95% CI 1.2-2.1, p = 0.002) and OS (HR 1.5, 95% CI 1.1-2, p = 0.014). PTENlow tumors showed overexpression of neuroendocrine, cell cycle, and DNA repair gene signatures, reduced expression of the androgen receptor pathway, and a distinct immune microenvironment. Using microarray data from the CHAARTED trial, we developed a PTEN-low related signature, independently associated with CRPC-FS (HR 1.5, 95% CI 1-2.3, p = 0.036) and OS (HR 1.9, C1 1.2-2.9, p = 0.005), and identified targets for potential therapies in PTEN-altered tumors. We conclude that PTENlow correlates with an aggressive clinical outcome in mHSPC patients and is associated with a unique transcriptional profile. These findings further support the investigation of novel therapeutic strategies for patients with PTEN alterations.MDPI2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/20200INTERNATIONAL JOURNAL OF MOLECULAR SCIENCESISSN: 16616596ISSNe: 14220067reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p202002026-06-07T16:35:31Z
dc.title.none.fl_str_mv Clinical and Transcriptomic Characterization of Metastatic Hormone-Sensitive Prostate Cancer Patients with Low PTEN Expression
title Clinical and Transcriptomic Characterization of Metastatic Hormone-Sensitive Prostate Cancer Patients with Low PTEN Expression
spellingShingle Clinical and Transcriptomic Characterization of Metastatic Hormone-Sensitive Prostate Cancer Patients with Low PTEN Expression
Garcia de Herreros M
hormone-sensitive prostate cancer
PTEN
biomarkers
androgen deprivation therapy
docetaxel
androgen receptor signaling inhibitors
CHAARTED trial
title_short Clinical and Transcriptomic Characterization of Metastatic Hormone-Sensitive Prostate Cancer Patients with Low PTEN Expression
title_full Clinical and Transcriptomic Characterization of Metastatic Hormone-Sensitive Prostate Cancer Patients with Low PTEN Expression
title_fullStr Clinical and Transcriptomic Characterization of Metastatic Hormone-Sensitive Prostate Cancer Patients with Low PTEN Expression
title_full_unstemmed Clinical and Transcriptomic Characterization of Metastatic Hormone-Sensitive Prostate Cancer Patients with Low PTEN Expression
title_sort Clinical and Transcriptomic Characterization of Metastatic Hormone-Sensitive Prostate Cancer Patients with Low PTEN Expression
dc.creator.none.fl_str_mv Garcia de Herreros M
Jiménez N
Padrosa J
Aversa C
Ferrer-Mileo L
García-Esteve S
Rodríguez-Carunchio L
Trias I
Fernández-Mañas L
Marín-Aguilera M
Altamirano M
Mazariegos M
Font A
Rodriguez-Vida A
Climent MÁ
Cros S
Chirivella I
Figols M
Sala-González N
Ruiz de Porras V
Pardo JC
Prat A
Reig Ò
Mellado B
author Garcia de Herreros M
author_facet Garcia de Herreros M
Jiménez N
Padrosa J
Aversa C
Ferrer-Mileo L
García-Esteve S
Rodríguez-Carunchio L
Trias I
Fernández-Mañas L
Marín-Aguilera M
Altamirano M
Mazariegos M
Font A
Rodriguez-Vida A
Climent MÁ
Cros S
Chirivella I
Figols M
Sala-González N
Ruiz de Porras V
Pardo JC
Prat A
Reig Ò
Mellado B
author_role author
author2 Jiménez N
Padrosa J
Aversa C
Ferrer-Mileo L
García-Esteve S
Rodríguez-Carunchio L
Trias I
Fernández-Mañas L
Marín-Aguilera M
Altamirano M
Mazariegos M
Font A
Rodriguez-Vida A
Climent MÁ
Cros S
Chirivella I
Figols M
Sala-González N
Ruiz de Porras V
Pardo JC
Prat A
Reig Ò
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
dc.subject.none.fl_str_mv hormone-sensitive prostate cancer
PTEN
biomarkers
androgen deprivation therapy
docetaxel
androgen receptor signaling inhibitors
CHAARTED trial
topic hormone-sensitive prostate cancer
PTEN
biomarkers
androgen deprivation therapy
docetaxel
androgen receptor signaling inhibitors
CHAARTED trial
description Alterations in the PTEN tumor suppressor gene are common in prostate cancer. They have been associated with a more aggressive disease and poor outcomes and potential benefit of targeted therapies. The purpose of this work is to study the clinical and transcriptional landscapes associated to low PTEN mRNA expression in metastatic hormone-sensitive prostate cancer (mHSPC) patients. A multicenter biomarker ambispective study was performed in mHSPC patients. PTEN mRNA expression was assessed by nCounter in formalin-fixed paraffin-embedded tumor samples. PTENlow status was defined by a previously validated cut-off and was correlated with castration-resistant prostate cancer (CRPC)-free survival (CRPC-FS) (primary endpoint) and overall survival (OS). RNA-Seq was performed to molecularly characterize PTENlow vs. PTENwt tumors. A total of 380 patients were included, 350 eligible. PTENlow was observed in 28.2% of patients and was independently associated with shorter CRPC-FS (HR 1.6, 95% CI 1.2-2.1, p = 0.002) and OS (HR 1.5, 95% CI 1.1-2, p = 0.014). PTENlow tumors showed overexpression of neuroendocrine, cell cycle, and DNA repair gene signatures, reduced expression of the androgen receptor pathway, and a distinct immune microenvironment. Using microarray data from the CHAARTED trial, we developed a PTEN-low related signature, independently associated with CRPC-FS (HR 1.5, 95% CI 1-2.3, p = 0.036) and OS (HR 1.9, C1 1.2-2.9, p = 0.005), and identified targets for potential therapies in PTEN-altered tumors. We conclude that PTENlow correlates with an aggressive clinical outcome in mHSPC patients and is associated with a unique transcriptional profile. These findings further support the investigation of novel therapeutic strategies for patients with PTEN alterations.
publishDate 2025
dc.date.none.fl_str_mv 2025
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/20200
url https://incliva.portalinvestigacion.com/publicaciones/20200
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 MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN: 16616596
ISSNe: 14220067
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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