Cargando…

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

SIMPLE SUMMARY: The combination of androgen deprivation therapy (ADT) with docetaxel (DX) or/and with novel anti-androgen receptor therapies have become standards for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, metastatic PC remains incurable, and bi...

Descripción completa

Detalles Bibliográficos
Autores principales: Jiménez, Natalia, Reig, Òscar, Marín-Aguilera, Mercedes, Aversa, Caterina, Ferrer-Mileo, Laura, Font, Albert, Rodriguez-Vida, Alejo, Climent, Miguel Ángel, Cros, Sara, Chirivella, Isabel, Domenech, Montserrat, Figols, Mariona, González-Billalabeitia, Enrique, Jiménez Peralta, Daniel, Rodríguez-Carunchio, Leonardo, García-Esteve, Samuel, Garcia de Herreros, Marta, Ribal, Maria J., Prat, Aleix, Mellado, Begoña
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9564355/
https://www.ncbi.nlm.nih.gov/pubmed/36230681
http://dx.doi.org/10.3390/cancers14194757
_version_ 1784808622374518784
author Jiménez, Natalia
Reig, Òscar
Marín-Aguilera, Mercedes
Aversa, Caterina
Ferrer-Mileo, Laura
Font, Albert
Rodriguez-Vida, Alejo
Climent, Miguel Ángel
Cros, Sara
Chirivella, Isabel
Domenech, Montserrat
Figols, Mariona
González-Billalabeitia, Enrique
Jiménez Peralta, Daniel
Rodríguez-Carunchio, Leonardo
García-Esteve, Samuel
Garcia de Herreros, Marta
Ribal, Maria J.
Prat, Aleix
Mellado, Begoña
author_facet Jiménez, Natalia
Reig, Òscar
Marín-Aguilera, Mercedes
Aversa, Caterina
Ferrer-Mileo, Laura
Font, Albert
Rodriguez-Vida, Alejo
Climent, Miguel Ángel
Cros, Sara
Chirivella, Isabel
Domenech, Montserrat
Figols, Mariona
González-Billalabeitia, Enrique
Jiménez Peralta, Daniel
Rodríguez-Carunchio, Leonardo
García-Esteve, Samuel
Garcia de Herreros, Marta
Ribal, Maria J.
Prat, Aleix
Mellado, Begoña
author_sort Jiménez, Natalia
collection PubMed
description SIMPLE SUMMARY: The combination of androgen deprivation therapy (ADT) with docetaxel (DX) or/and with novel anti-androgen receptor therapies have become standards for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, metastatic PC remains incurable, and biomarkers for individual treatment selection are needed. We propose here that molecular alterations associated with castration resistance may predict the clinical evolution of mHSPC patients. To test this hypothesis, we designed a custom expression panel of 184 genes and tested it in tumor biopsies from patients with mHSPC treated with ADT+DX. We found that AR and ESR signatures and ESR2 gene expression correlate with a good prognosis. The lower expression of TSG (PTEN, TP53 and RB1) signature, as well as high ARV7 and low RB1 gene expression, were associated with adverse clinical outcomes. The usefulness of transcriptomic analysis of such signatures as a strategy for personalized treatment selection should be further explored. ABSTRACT: (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.
format Online
Article
Text
id pubmed-9564355
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-95643552022-10-15 Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel Jiménez, Natalia Reig, Òscar Marín-Aguilera, Mercedes Aversa, Caterina Ferrer-Mileo, Laura Font, Albert Rodriguez-Vida, Alejo Climent, Miguel Ángel Cros, Sara Chirivella, Isabel Domenech, Montserrat Figols, Mariona González-Billalabeitia, Enrique Jiménez Peralta, Daniel Rodríguez-Carunchio, Leonardo García-Esteve, Samuel Garcia de Herreros, Marta Ribal, Maria J. Prat, Aleix Mellado, Begoña Cancers (Basel) Article SIMPLE SUMMARY: The combination of androgen deprivation therapy (ADT) with docetaxel (DX) or/and with novel anti-androgen receptor therapies have become standards for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, metastatic PC remains incurable, and biomarkers for individual treatment selection are needed. We propose here that molecular alterations associated with castration resistance may predict the clinical evolution of mHSPC patients. To test this hypothesis, we designed a custom expression panel of 184 genes and tested it in tumor biopsies from patients with mHSPC treated with ADT+DX. We found that AR and ESR signatures and ESR2 gene expression correlate with a good prognosis. The lower expression of TSG (PTEN, TP53 and RB1) signature, as well as high ARV7 and low RB1 gene expression, were associated with adverse clinical outcomes. The usefulness of transcriptomic analysis of such signatures as a strategy for personalized treatment selection should be further explored. ABSTRACT: (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. MDPI 2022-09-29 /pmc/articles/PMC9564355/ /pubmed/36230681 http://dx.doi.org/10.3390/cancers14194757 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jiménez, Natalia
Reig, Òscar
Marín-Aguilera, Mercedes
Aversa, Caterina
Ferrer-Mileo, Laura
Font, Albert
Rodriguez-Vida, Alejo
Climent, Miguel Ángel
Cros, Sara
Chirivella, Isabel
Domenech, Montserrat
Figols, Mariona
González-Billalabeitia, Enrique
Jiménez Peralta, Daniel
Rodríguez-Carunchio, Leonardo
García-Esteve, Samuel
Garcia de Herreros, Marta
Ribal, Maria J.
Prat, Aleix
Mellado, Begoña
Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel
title Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel
title_full Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel
title_fullStr Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel
title_full_unstemmed Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel
title_short Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel
title_sort transcriptional profile associated with clinical outcomes in metastatic hormone-sensitive prostate cancer treated with androgen deprivation and docetaxel
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9564355/
https://www.ncbi.nlm.nih.gov/pubmed/36230681
http://dx.doi.org/10.3390/cancers14194757
work_keys_str_mv AT jimeneznatalia transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT reigoscar transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT marinaguileramercedes transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT aversacaterina transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT ferrermileolaura transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT fontalbert transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT rodriguezvidaalejo transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT climentmiguelangel transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT crossara transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT chirivellaisabel transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT domenechmontserrat transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT figolsmariona transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT gonzalezbillalabeitiaenrique transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT jimenezperaltadaniel transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT rodriguezcarunchioleonardo transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT garciaestevesamuel transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT garciadeherrerosmarta transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT ribalmariaj transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT prataleix transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel
AT melladobegona transcriptionalprofileassociatedwithclinicaloutcomesinmetastatichormonesensitiveprostatecancertreatedwithandrogendeprivationanddocetaxel