Homologous recombination deficiency score served as an independent prognosis factor in esophageal squamous cell carcinoma.

e16080 Background: Homologous recombination deficiency (HRD) is a functional impairment of the homologous recombination repair (HRR) pathway, pivotal for mending DNA double-strand breaks, contributing significantly to cancer-associated genomic instability. While BRCA mutations traditionally underlie HRR defects, recent studies highlight varied responses to poly (ADP-ribose) polymerase (PARP) inhibitors based on specific HRR-related gene alterations. Despite HRD's relevance in various cancers, its role in esophageal squamous cell carcinoma (ESCC) remains underexplored. Methods: We conducted a retrospective analysis of HRD scores in 96 ESCC patients, assessing correlations with clinical characteristics and survival outcomes. Genomic sequencing was performed using a customized superHRD NGS panel. HRD scores were calculated based on 54,000 single-nucleotide polymorphisms, employing Kruskal-Wallis ranksum tests and two cut-off points for quantitative analysis. Kaplan-Meier survival and Cox regression model were employed to evaluate disease-free survival (DFS) and overall survival (OS). Results: Higher HRD scores correlated with advanced tumor stages, recurrence, and specific gene mutations ( TP53 and ABCB1). APC mutations were associated with lower HRD scores. Patients with high HRD scores demonstrated significantly shorter disease-free survival (DFS) and a trend towards shorter overall survival (OS), especially those who did not receive adjuvant therapy, emphasizing HRD's prognostic value. Conversely, HRD-high patients undergoing adjuvant therapy showed a tendency towards extended OS. Multivariate analysis identified HRD as an independent prognostic factor (HR = 2.814 for recurrence, HR = 1.772 for death). Validation with The Cancer Genome Atlas (TCGA) ESCC dataset supported our findings. Conclusions: This study unveils associations between HRD scores, clinical characteristics, and genomic mutations in ESCC, emphasizing HRD's potential as a prognostic biomarker. HRD assessment may aid in patient stratification and personalized treatment strategies. Future investigations should explore underlying molecular mechanisms and therapeutic implications of HRD-associated pathways in ESCC management.