Homologous recombination deficiency score is an independent prognostic factor in esophageal squamous cell carcinoma

Abstract

Homologous recombination deficiency (HRD) represents an impairment in the homologous recombination repair (HRR) pathway, crucial for repairing DNA double-strand breaks and contributing to genomic instability in cancer. The HRD score may be a more reliable biomarker than HRR-related gene mutations for identifying patients sensitive to poly(ADP-ribose) polymerase inhibitors. Despite its relevance in various cancers, the HRD score remains underexplored in esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed HRD scores in 96 ESCC patients, examining correlations with clinical characteristics and survival outcomes, and validated our findings using the TCGA dataset. Genomic sequencing utilized a custom superHRD next-generation sequencing panel, and HRD scores were calculated from 54,000 single-nucleotide polymorphisms using Kruskal–Wallis rank-sum tests and two cut-off points for analysis. Higher HRD scores correlated with advanced tumor stages, recurrence, and mutations in TP53 and ABCB1, while APC mutations were linked to lower HRD scores. Patients with high HRD scores had significantly shorter disease-free survival (p = 0.013) and a trend toward shorter overall survival (OS) (p = 0.005), particularly those not receiving adjuvant therapy. Conversely, HRD-high patients undergoing adjuvant therapy showed a trend toward longer OS (p = 0.015). Multivariate analysis identified HRD as an independent prognostic factor (hazard ratio = 2.814 for recurrence, p = 0.015). Validation with the TCGA dataset supported these findings. This study highlights the associations between HRD scores, clinical characteristics, and genomic mutations in ESCC, suggesting HRD as a potential prognostic biomarker. HRD assessment may aid in patient stratification and personalized treatment strategies, warranting further investigation to validate the therapeutic implications of HRD scores in ESCC.