Wang Hongxia, Zhao Wenhong, Zhou Wenhao, Wang Na, Li Yijie, Qin Kaiyun, Jia Jingde, Wang Jiaqian, Song Congcong, Yu Yu, Zhang Fenghua, Cui Xu, Zhao Lanlan, Luo Haitao, Zhang Zhengmao
Department of Gynecology, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China.
Shenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co., Ltd, Shenzhen, 518000, China.
Hum Genomics. 2025 Aug 31;19(1):104. doi: 10.1186/s40246-025-00806-w.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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