Shi Yaqin, Shen Meng, Xu Mengdan, Tao Min, Chen Kai, Zhu Qingqing
Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China.
Int J Gen Med. 2022 May 13;15:4925-4936. doi: 10.2147/IJGM.S350971. eCollection 2022.
The RAD51 family of genes, including RAD51 and the five RAD51-like paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3), are known to be crucially associated with DNA damage repair pathway. Increasing evidence indicated that RAD51 family members were implicated in breast cancer tumorigenesis. However, their biological roles and prognostic values in breast cancer have yet to be clarified.
In this study, by using the Oncomine and GEPIA databases, we explored the transcriptional levels of RAD51 family members in breast cancer. Besides, the associations between RAD51 family expression and clinical features were evaluated by using the UALCAN database and Kaplan-Meier (KM) Plotter. We also analyzed the mutations of the RAD51 family and differentially altered genes from the cBioPortal database.
We found that RAD51 mRNA was significantly elevated in breast cancer samples than in normal tissues, while XRCC2 mRNA was downregulated. Besides, a remarkable correlation was detected between the expression of RAD51/RAD51B/XRCC2 genes and the breast cancer stage. Survival analysis utilizing the KM Plotter indicated that high RAD51 and XRCC3 mRNA was associated with a poor prognosis. Conversely, RFS data suggested that high levels of RAD51B/RAD51C/RAD51D/XRCC2 were associated with a favorable prognosis. Moreover, a high genetic variation rate of RAD51C (7%) was detected in breast cancer patients.
Conclusively, we implied that RAD51 and XRCC3 might be potential targets for precision therapy in breast cancer and the RAD51B/RAD51C/RAD51D/XRCC2 genes have significant values for breast cancer prognosis.
已知RAD51基因家族，包括RAD51以及五个RAD51样旁系同源基因（RAD51B、RAD51C、RAD51D、XRCC2和XRCC3）与DNA损伤修复途径密切相关。越来越多的证据表明，RAD51家族成员与乳腺癌的肿瘤发生有关。然而，它们在乳腺癌中的生物学作用和预后价值尚未明确。
在本研究中，我们通过使用Oncomine和GEPIA数据库，探索了RAD51家族成员在乳腺癌中的转录水平。此外，使用UALCAN数据库和Kaplan-Meier（KM）绘图仪评估了RAD51家族表达与临床特征之间的关联。我们还从cBioPortal数据库分析了RAD51家族的突变和差异改变的基因。
我们发现，与正常组织相比，乳腺癌样本中RAD51 mRNA显著升高，而XRCC2 mRNA下调。此外，检测到RAD51/RAD51B/XRCC2基因的表达与乳腺癌分期之间存在显著相关性。利用KM绘图仪进行的生存分析表明，高RAD51和XRCC3 mRNA与预后不良相关。相反，无复发生存（RFS）数据表明，高水平的RAD51B/RAD51C/RAD51D/XRCC2与良好的预后相关。此外，在乳腺癌患者中检测到RAD51C的高基因变异率（7%）。
总之，我们认为RAD51和XRCC3可能是乳腺癌精准治疗的潜在靶点，而RAD51B/RAD51C/RAD51D/XRCC2基因对乳腺癌预后具有重要价值。
