Prognostic Relevance of Clinical and Tumor Mutational Profile in High-Grade Serous Ovarian Cancer

High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer, accounting for approximately 70% of cases. This study investigates genetic mutations and their associations with overall survival (OS), complete cytoreduction (R0), and platinum response in patients...

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Autores: Martin-Vallejo, Javier, Berenguer-Mari, Juan Ramon, Bosch-Romeu, Raquel, Sierra-Roca, Julia, Tadeo-Cervera, Irene, Pardo, Juan, Falco, Antonio, Molina-Bellido, Patricia, Laforga, Juan Bautista, Clemente-Perez, Pedro Antonio, Gasent-Blesa, Juan Manuel, Climent, Joan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p19376
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/19376
Access Level:acceso abierto
Palabra clave:HGSOC
NGS
<italic>ERBB4</italic> mutations
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spelling Prognostic Relevance of Clinical and Tumor Mutational Profile in High-Grade Serous Ovarian CancerMartin-Vallejo, JavierBerenguer-Mari, Juan RamonBosch-Romeu, RaquelSierra-Roca, JuliaTadeo-Cervera, IrenePardo, JuanFalco, AntonioMolina-Bellido, PatriciaLaforga, Juan BautistaClemente-Perez, Pedro AntonioGasent-Blesa, Juan ManuelCliment, JoanHGSOCNGS<italic>ERBB4</italic> mutationsHigh-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer, accounting for approximately 70% of cases. This study investigates genetic mutations and their associations with overall survival (OS), complete cytoreduction (R0), and platinum response in patients undergoing either primary debulking surgery followed by adjuvant chemotherapy (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (NACT). Genetic analysis was performed on 43 primary HGSOC tumor samples using targeted massive parallel sequencing via next-generation sequencing (NGS). Clinical and molecular data were evaluated collectively and through subgroup comparisons between PDS and NACT cohorts. All analyzed samples harbored genetic alterations. Univariate survival analysis revealed that the total number of mutations (p = 0.0035), as well as mutations in HRAS (p = 0.044), FLT3 (p = 0.023), TP53 (p = 0.03), and ERBB4 (p = 0.007), were significantly associated with poorer OS. Multivariate Cox regression integrating clinical and molecular data confirmed that ERBB4 mutations are independently associated with adverse outcomes. These findings reveal a distinctive mutational landscape between the PDS and NACT groups and suggest that ERBB4 alterations may define a particularly aggressive tumor phenotype. This study contributes to a deeper understanding of HGSOC biology and may support the development of novel therapeutic targets and personalized treatment strategies in the context of precision oncology.MDPI2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/19376INTERNATIONAL JOURNAL OF MOLECULAR SCIENCESISSN: 16616596ISSNe: 14220067reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p193762026-06-11T12:45:17Z
dc.title.none.fl_str_mv Prognostic Relevance of Clinical and Tumor Mutational Profile in High-Grade Serous Ovarian Cancer
title Prognostic Relevance of Clinical and Tumor Mutational Profile in High-Grade Serous Ovarian Cancer
spellingShingle Prognostic Relevance of Clinical and Tumor Mutational Profile in High-Grade Serous Ovarian Cancer
Martin-Vallejo, Javier
HGSOC
NGS
<italic>ERBB4</italic> mutations
title_short Prognostic Relevance of Clinical and Tumor Mutational Profile in High-Grade Serous Ovarian Cancer
title_full Prognostic Relevance of Clinical and Tumor Mutational Profile in High-Grade Serous Ovarian Cancer
title_fullStr Prognostic Relevance of Clinical and Tumor Mutational Profile in High-Grade Serous Ovarian Cancer
title_full_unstemmed Prognostic Relevance of Clinical and Tumor Mutational Profile in High-Grade Serous Ovarian Cancer
title_sort Prognostic Relevance of Clinical and Tumor Mutational Profile in High-Grade Serous Ovarian Cancer
dc.creator.none.fl_str_mv Martin-Vallejo, Javier
Berenguer-Mari, Juan Ramon
Bosch-Romeu, Raquel
Sierra-Roca, Julia
Tadeo-Cervera, Irene
Pardo, Juan
Falco, Antonio
Molina-Bellido, Patricia
Laforga, Juan Bautista
Clemente-Perez, Pedro Antonio
Gasent-Blesa, Juan Manuel
Climent, Joan
author Martin-Vallejo, Javier
author_facet Martin-Vallejo, Javier
Berenguer-Mari, Juan Ramon
Bosch-Romeu, Raquel
Sierra-Roca, Julia
Tadeo-Cervera, Irene
Pardo, Juan
Falco, Antonio
Molina-Bellido, Patricia
Laforga, Juan Bautista
Clemente-Perez, Pedro Antonio
Gasent-Blesa, Juan Manuel
Climent, Joan
author_role author
author2 Berenguer-Mari, Juan Ramon
Bosch-Romeu, Raquel
Sierra-Roca, Julia
Tadeo-Cervera, Irene
Pardo, Juan
Falco, Antonio
Molina-Bellido, Patricia
Laforga, Juan Bautista
Clemente-Perez, Pedro Antonio
Gasent-Blesa, Juan Manuel
Climent, Joan
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HGSOC
NGS
<italic>ERBB4</italic> mutations
topic HGSOC
NGS
<italic>ERBB4</italic> mutations
description High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer, accounting for approximately 70% of cases. This study investigates genetic mutations and their associations with overall survival (OS), complete cytoreduction (R0), and platinum response in patients undergoing either primary debulking surgery followed by adjuvant chemotherapy (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (NACT). Genetic analysis was performed on 43 primary HGSOC tumor samples using targeted massive parallel sequencing via next-generation sequencing (NGS). Clinical and molecular data were evaluated collectively and through subgroup comparisons between PDS and NACT cohorts. All analyzed samples harbored genetic alterations. Univariate survival analysis revealed that the total number of mutations (p = 0.0035), as well as mutations in HRAS (p = 0.044), FLT3 (p = 0.023), TP53 (p = 0.03), and ERBB4 (p = 0.007), were significantly associated with poorer OS. Multivariate Cox regression integrating clinical and molecular data confirmed that ERBB4 mutations are independently associated with adverse outcomes. These findings reveal a distinctive mutational landscape between the PDS and NACT groups and suggest that ERBB4 alterations may define a particularly aggressive tumor phenotype. This study contributes to a deeper understanding of HGSOC biology and may support the development of novel therapeutic targets and personalized treatment strategies in the context of precision oncology.
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://fisabio.portalinvestigacion.com/publicaciones/19376
url https://fisabio.portalinvestigacion.com/publicaciones/19376
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-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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