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Publications

Journal Article Epublish

PubMed: 40806544 DOI: 10.3390/ijms26157416

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

Int J Mol Sci 26(15)

Authors: Javier Martín-Vallejo, Juan Ramón Berenguer-Marí, Raquel Bosch-Romeu, Julia Sierra-Roca, Irene Tadeo-Cervera, Juan Pardo, Antonio Falcó, Patricia Molina-Bellido, Juan Bautista Laforga, Pedro Antonio Clemente-Pérez, Juan Manuel Gasent-Blesa, Joan Climent

Affiliations

  • Department of Obstetrics and Gynecology, Hospital de Denia, 03700 Alicante, Spain.
  • Department of Medical Oncology, Hospital de Denia, 03700 Alicante, Spain.
  • ESI International Chair@CEU-UCH, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Spain.
  • Department of Obstetrics and Gynecology, La Ribera Salud, 46015 Sueca, Spain.
  • ECMOR Chair@CEU-UCH, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Spain. PASAPTA Department at Veterinary School, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Spain.
  • Department of Pathology, Hospital de Denia, 03700 Alicante, Spain.
  • ECMOR Chair@CEU-UCH, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Spain.
  • PASAPTA Department at Veterinary School, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Spain.
  • Biomedical Research Institute, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Spain.

Abstract

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.

MeSH

Neoplasms, Drug Therapy, Chemotherapy, Adjuvant, Ovarian Neoplasms, Therapeutics, Mutation, Chemotherapy