Ding Yue, Ye Zheng, Ding Bo, Feng Songwei, Zhang Yang, Shen Yang
Department of Obstetrics and Gynaecology, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009, China.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
Mol Biotechnol. 2025 Jun;67(6):2428-2442. doi: 10.1007/s12033-024-01207-5. Epub 2024 Jun 10.
Ovarian cancer has poor response rates to immune checkpoint blockade (ICB) therapy, despite the use of genomic sequencing to identify molecular targets. Homologous recombination deficiency (HRD) is a conventional indicator of genomic instability (GI) and has been used as a marker for targeted therapies. Indicators reflecting HRD status have shown potential in predicting the efficacy of ICB treatment. Public databases, including TCGA, ICGC, and GEO, were used to obtain data. HRD scores, neoantigen load, and TMB were obtained from the TCGA cohort. Candidate biomarkers were validated in multiple databases, such as the Imvigor210 immunotherapy cohort and the open-source single-cell sequencing database. Immunohistochemistry was performed to further validate the results in independent cohorts. CXCL10, CXCL11, and CXCL13 were found to be significantly upregulated in HRD tumors and exhibited prognostic value. A comprehensive analysis of the tumor immune microenvironment (TIME) revealed that CXCL13 expression positively correlated with neoantigen load and immune cell infiltration. In addition, single-cell sequencing data and clinical trial results supported the utility of CXCL13 as a biomarker for ICB therapy. Not only does CXCL13 serve as a biomarker reflecting HRD status, but it also introduces a potentially novel perspective on prognostic biomarkers for ICB in ovarian cancer.
尽管使用基因组测序来识别分子靶点，但卵巢癌对免疫检查点阻断（ICB）治疗的反应率较低。同源重组缺陷（HRD）是基因组不稳定（GI）的传统指标，并已被用作靶向治疗的标志物。反映HRD状态的指标已显示出预测ICB治疗疗效的潜力。使用包括TCGA、ICGC和GEO在内的公共数据库来获取数据。从TCGA队列中获得HRD评分、新抗原负荷和肿瘤突变负荷（TMB）。候选生物标志物在多个数据库中进行了验证，如Imvigor210免疫治疗队列和开源单细胞测序数据库。进行免疫组织化学以在独立队列中进一步验证结果。发现CXCL10、CXCL11和CXCL13在HRD肿瘤中显著上调，并具有预后价值。对肿瘤免疫微环境（TIME）的综合分析表明，CXCL13表达与新抗原负荷和免疫细胞浸润呈正相关。此外，单细胞测序数据和临床试验结果支持CXCL13作为ICB治疗生物标志物的效用。CXCL13不仅作为反映HRD状态的生物标志物，而且还为卵巢癌ICB的预后生物标志物引入了一个潜在的新视角。
