廖宁团队揭示激素受体阳性乳腺癌细胞周期相关基因突变特征及临床意义
对于激素受体阳性HER2阴性乳腺癌，尤其内分泌治疗耐药患者，通常可见细胞周期相关基因突变，从而引起癌细胞有丝分裂周期失控。
2021年8月27日，日本乳腺癌学会《乳腺癌》在线发表广东省人民医院赖建国、陈博、廖宁等学者的研究报告，对激素受体阳性HER2阴性乳腺癌细胞周期相关基因突变特征及其临床意义进行了综合分析。
该单中心回顾研究对广东省人民医院321例激素受体阳性HER2阴性乳腺癌患者肿瘤标本的15个细胞周期关键基因进行大规模并行测序和基因组分析，并与国际乳腺癌分子分类联盟1347例激素受体阳性HER2阴性乳腺癌患者的细胞周期关键基因测序数据进行比较。通过多因素比例风险回归模型分析，确定细胞周期相关基因突变对患者总生存的影响。利用基因组荟萃分析数据库，进一步探索细胞周期相关基因的功能作用。
结果，根据多因素比例风险回归模型分析，五个关键的细胞周期相关基因CDK4、CCND1、CDKN1A、CDKN1C、CHEK2被确定为激素受体阳性HER2阴性乳腺癌患者总生存的独立预后因素。
此外，根据五个细胞周期相关基因风险评分，可将患者有效地分为低风险组和高风险组，5年总生存显著不同（P<0.0001）。
细胞周期相关基因的潜在功能通路包括细胞有丝分裂周期、DNA合成前期的细胞周期蛋白D相关事件、DNA合成前期进入DNA合成期的调控。
因此，该单中心回顾研究结果表明，五个关键的细胞周期相关基因是中国激素受体阳性HER2阴性乳腺癌患者总生存的独立预后因素，可能有助于指导激素受体阳性HER2阴性乳腺癌患者的个体化精准肿瘤治疗方案，故有必要进一步开展多中心大样本前瞻研究进行验证。
Breast Cancer. 2021 Aug 27. Online ahead of print.
Integrated analysis of cell cycle-related genes in HR+/HER2- breast cancer.
Lai J, Chen B, Li Y, Lin X, Li M, Liu J, Liao N.
Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China; Burning Rock Biotech, Guangzhou, China.
PURPOSE: This 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).
METHODS: A 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.
RESULTS: Based on multivariate Cox regression analysis, a set of five key CCGs (CDK4, CCND1, CDKN1A, CDKN1C, and CHEK2) 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.
CONCLUSION: We 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.
KEYWORDS: Alteration; Breast cancer; Cell cycle; Gene; Prognosis
PMID: 34449047
DOI: 10.1007/s12282-021-01289-y