Genomic and transcriptomic data reveal molecular differences between homologous recombination deficiency subgroups in Chinese ovarian cancer patients.

Ovarian cancer (OV) has the highest mortality rate among gynecological cancers and shows varied responses to chemotherapy combined with PARP inhibitors based on homologous recombination deficiency (HRD) subtypes. This study enrolled 143 Chinese OV patients to determine the HRD score grouping threshold using genomic features, dividing patients into HRD-high and HRD-low groups. Multi-omics sequencing was conducted on 70 patients receiving adjuvant chemotherapy with PARP inhibitors. In this study, TP53 mutations enriched in the HRD-high group, while ARID1A, PIK3CA, and PTEN mutations were more common in the HRD-low group. HRD-high patients exhibited stronger immune activation, including elevated STAT1 expression, HLA signatures, and increased M1 macrophage infiltration, correlating with better prognosis. Additionally, peripheral blood analysis revealed higher bMSI and maxVAF levels in HRD-low patients compared to HRD-high patients, suggesting ctDNA as a potential tool for dynamic monitoring post-treatment. This study identified distinct molecular and immune profiles between HRD subgroups in Chinese ovarian cancer patients. Patients with HRD-high and STAT1 expression ≥ 74 suggests PARPi benefit.