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

## TL;DR

This study explores how genetic mutations in high-grade serous ovarian cancer affect survival and treatment outcomes, identifying ERBB4 mutations as a marker for poor prognosis.

## Contribution

The study identifies ERBB4 mutations as an independent prognostic factor in high-grade serous ovarian cancer.

## Key findings

- ERBB4 mutations are independently associated with worse overall survival in HGSOC patients.
- The PDS and NACT treatment groups show distinct mutational profiles.
- Multiple mutations, including HRAS, FLT3, TP53, and ERBB4, correlate with poorer survival outcomes.

## 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.