肾透明细胞癌（KIRC）是一种常见的恶性肿瘤，具有高度的异质性和遗传不稳定性。同源重组缺陷（HRD）产生的DNA双链断裂是基因组不稳定性的已知贡献因素，可促进肿瘤发展。然而，目前尚不清楚与HRD相关的分子特征在KIRC中是否具有预测作用。发现队列包括来自癌症基因组图谱数据库的501名KIRC患者。HRD患者的基因组和转录组数据用于全面分析。单细胞RNA测序（scRNA-seq）用于验证大规模RNA测序的测试结果。在本研究中，高HRD评分的患者与低HRD评分的患者相比有更差的预后。DNA损伤应答信号通路和免疫相关信号通路在HRD阳性亚组中显著富集。进一步对肿瘤微环境（TME）进行全面分析发现，耗竭的CD8+ T细胞的信号在HRD阳性亚组中富集。最后，scRNA-seq分析证实HRD阳性患者中免疫相关信号通路的上调。综上所述，本研究不仅证明了高HRD评分是KIRC患者有效的预后生物标志物，还揭示了HRD阳性肿瘤中的TME。版权：© He等。

Kidney renal clear cell carcinoma (KIRC) is a frequent malignant tumor characterized by a high degree of heterogeneity and genetic instability. DNA double-strand breaks generated by homologous recombination deficit (HRD) are a well-known contributor to genomic instability, which can encourage tumor development. It is not known, however, whether the molecular characteristics linked with HRD have a predictive role in KIRC. The discovery cohort comprised 501 KIRC patients from The Cancer Genome Atlas database. Genome and transcriptome data of HRD patients were used for comprehensive analysis. Single cell RNA sequencing (scRNA-seq) was used to verify the test results of bulk RNA-seq. In the present study, patients with a high HRD score had a worse prognosis compared with those with a low HRD score. The DNA damage response signaling pathways and immune-related signaling pathways were notably enriched in the HRD-positive subgroup. Further comprehensive analysis of the tumor microenvironment (TME) revealed that the signal of exhausted CD8+ T cells was enriched in the HRD-positive subgroup. Finally, scRNA-seq analyses confirmed that the immune-related signaling pathways were upregulated in HRD-positive patients. In conclusion, the present study not only demonstrated that a high HRD score is a valid prognostic biomarker in KIRC patients, but also revealed the TME in HRD-positive tumors.Copyright: © He et al.