Dong Lin, Li Lin, Zhu Linyan, Xu Fei, Zhang Rumeng, Li Qiushuang, Zhu Yong, Zeng Zhutian, Ding Keshuo
Department of Pathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China.
Department of Pathology, Tongling People's Hospital, Tongling, Anhui, China.
Biomol Biomed. 2024 Dec 11;25(1):71-81. doi: 10.17305/bb.2024.10448.
There remains ongoing debate regarding the association of homologous recombination deficiency (HRD) with patient survival across various malignancies, highlighting the need for a comprehensive understanding of HRD's role in different cancer types. Based on data from databases, we conducted a multivariable omics analysis on HRD in 33 cancer types, focusing mainly on 23 cancers in which HRD was significantly associated with patient overall survival (OS) rates. This analysis included the mechanisms related to patient prognosis, gene expression, gene mutation, and signaling pathways. In this study, HRD was found to be significantly associated with patient prognosis, but its impact varied among different cancers. HRD was linked to different outcomes for patients with distinct tumor subtypes and was correlated with clinical features such as clinical stage and tumor grade. Driver gene mutations, including TP53, MUC4, KRAS, HRAS, FLG, ANK3, BRCA2, ATRX, FGFR3, NFE2L2, MAP3K1, PIK3CA, CIC, FUBP1, ALB, CTNNB1, and MED12, were associated with HRD across specific cancer types. We also analyzed differentially expressed genes (DEGs) and differentially methylated regions (DMRs) in relation to HRD levels in these cancers. Furthermore, we explored the correlation between HRD and signaling pathways, as well as immune cell infiltration. Overall, our findings contribute to a comprehensive understanding of HRD's multifaceted role in cancer.
关于同源重组缺陷（HRD）与各种恶性肿瘤患者生存率之间的关联，目前仍存在争议，这凸显了全面了解HRD在不同癌症类型中作用的必要性。基于数据库中的数据，我们对33种癌症类型的HRD进行了多变量组学分析，主要聚焦于23种HRD与患者总生存率（OS）显著相关的癌症。该分析包括与患者预后、基因表达、基因突变和信号通路相关的机制。在本研究中，发现HRD与患者预后显著相关，但其影响在不同癌症中有所不同。HRD与不同肿瘤亚型患者的不同结局相关，并与临床分期和肿瘤分级等临床特征相关。驱动基因突变，包括TP53、MUC4、KRAS、HRAS、FLG、ANK3、BRCA2、ATRX、FGFR3、NFE2L2、MAP3K1、PIK3CA、CIC、FUBP1、ALB、CTNNB1和MED12，在特定癌症类型中与HRD相关。我们还分析了这些癌症中与HRD水平相关的差异表达基因（DEG）和差异甲基化区域（DMR）。此外，我们探讨了HRD与信号通路以及免疫细胞浸润之间的相关性。总体而言，我们的研究结果有助于全面了解HRD在癌症中的多方面作用。
