Integrated analysis of cell cycle-related genes in HR+/HER2− breast cancer
Integrated analysis of cell cycle-related genes in HR+/HER2− breast cancer
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HR/HER2™乳腺癌细胞周期相关基因的整合分析
DOI：
10.1007/s12282-021-01289-y
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发表时间：
2021
期刊：
影响因子：
4
通讯作者：
Ning Liao
中科院分区：
文献类型：
--
作者：
Jianguo Lai;Bo Chen;Yingzi Li;Xiaoyi Lin;Min Li;Jing Liu;Ning Liao
本研究旨在探讨激素受体阳性、人表皮生长因子受体2阴性乳腺癌(HR+/HER2−BC)中细胞周期相关基因(CCGs)突变的特点及意义。方法收集广东省人民医院1668例HR+/HER2−BC患者(n= 32 1)和 队列(n=1 347)。收集了HR+/HER2−BC患者的肿瘤样本，用于下一代测序分析，包括15个关键CCG。通过COX回归分析确定CCG改变与总存活率之间的关系。结果经多因素COX回归分析，5组关键CCG(CDK4、CCND1CDKN1a、CDKN1C和CHEK2)是HR+/HER2−BC患者的独立预后变量。此外，基于5个CCGs的风险评分被用来有效地将患者分为低风险组和高风险组(P<； 0.0001)。CCGs的潜在功能途径包括细胞周期、细胞周期蛋白D相关的G1期事件以及对有丝分裂细胞周期G1/S转变的调控。结论我们对HR+/HER2−BC患者CCGs进行了综合分析。它有可能指导HR+/HER2−BC患者的个体化精确肿瘤学治疗方案。
PurposeThis study aimed to explore the mutational characteristics and significance of cell cycle-related genes (CCGs) in hormone-receptor positive, human epidermal growth factor receptor 2 negative breast cancer (HR+/HER2− BC).MethodsA total of 1668 HR+/HER2− BC patients from the Guangdong Provincial People’s Hospital (GDPH) cohort (n= 321) and METABRIC cohort (n= 1347) were included. Tumor samples from HR+/HER2− BC patients were collected for a next-generation sequencing assay in GDPH cohort, including 15 key CCGs. The association between CCGs alterations and overall survival were identified via the Cox regression analysis. The functional roles of the CCGs were explored via the Metascape database.ResultsBased on multivariate Cox regression analysis, a set of five key CCGs (CDK4, CCND1, CDKN1A, CDKN1C, andCHEK2) were identified as independent prognostic variables in HR+/HER2− BC patients. Besides, the five-CCGs-based risk score was used to effectively classify patients into the low-risk and high-risk groups (P< 0.0001). The potential functional pathways of the CCGs included cell cycle, cyclin D associated events in G1, and regulation of G1/S transition of mitotic cell cycle.ConclusionWe performed the integrated analysis of the CCGs in HR+/HER2− BC patients. It has the potential to guide individualized precision oncology therapeutic schemes in HR+/HER2− BC patients.