Scientific Development and Planning Department, The First Hospital of Lanzhou University, Lanzhou, China.
College of Earth and Environmental Sciences, Lanzhou University, Lanzhou, China.
Breast Cancer. 2020 Sep;27(5):903-911. doi: 10.1007/s12282-020-01086-z. Epub 2020 Apr 27.
Triple-negative breast cancer (TNBC) is one of the leading causes of death among females around the world. However, the molecular mechanism of the disease among TNBC patients remains to be further studied.
In our study, four microarray data and two high throughput sequencing data were acquired from the GEO database, and the differentially expressed genes (DEGs) between TNBC and normal tissues had been analyzed. Analysis of functional enrichment and pathway enrichment of DEGs was conducted by the Funrich software, and protein-protein interaction (PPI) network gained from the STRING, and hub genes were confirmed by the Cytoscape. Kaplan-Meier plotter (KM plotter) online dataset had been used to analyze DEGs of overall survival (OS), and progression-free survival (PFS).
In total, 1638 DEGs were gained in our study covering 984 upregulated and 654 downregulated genes. Moreover, a PPI network was constructed, and cyclin-dependent kinase 1 (CDK1), cyclin B1 (CCNB1), and cyclin A2 (CCNA2) were found as top genes with higher node degrees. CDK1, CCNA2, and CCNB1were obviously enriched in the cell cycle. The top upregulated genes including CDK1, CCNB1, CCNA2, and PLK1 were overexpressed in TNBC, and correlated with worse OS in breast cancer. High expression of CCNB1 was correlated with worse PFS in TNBC (HR = 1.42, 95% CI: 1.04-1.94, P = 0.028). Besides, there was a correlation between CCNB1 and CDK1 in TNBC, as well as between CCNA2 and CDK1 (r = 0.804, P < 0.001; r = 0.577, P < 0.001, respectively).
Our results suggest that cyclin CDK1, CCNB1, and CCNA2 are overexpressed in TNBC and they could act as novel biomarkers for the diagnosis and treatment of TNBC.
三阴性乳腺癌（TNBC）是全球女性死亡的主要原因之一。然而，TNBC 患者疾病的分子机制仍有待进一步研究。
本研究从 GEO 数据库中获取了 4 个微阵列数据和 2 个高通量测序数据，并分析了 TNBC 与正常组织之间的差异表达基因（DEGs）。使用 Funrich 软件分析 DEGs 的功能富集和通路富集，使用 STRING 获得蛋白质-蛋白质相互作用（PPI）网络，并使用 Cytoscape 确认枢纽基因。Kaplan-Meier plotter（KM plotter）在线数据集用于分析总生存期（OS）和无进展生存期（PFS）的 DEGs。
本研究共获得 1638 个 DEGs，涵盖 984 个上调基因和 654 个下调基因。此外，构建了一个 PPI 网络，发现细胞周期蛋白依赖性激酶 1（CDK1）、细胞周期蛋白 B1（CCNB1）和细胞周期蛋白 A2（CCNA2）是具有较高节点度的顶级基因。CDK1、CCNA2 和 CCNB1 明显富集在细胞周期中。上调基因中包括 CDK1、CCNB1、CCNA2 和 PLK1，在 TNBC 中过度表达，与乳腺癌的 OS 较差相关。CCNB1 的高表达与 TNBC 的 PFS 较差相关（HR=1.42，95%CI：1.04-1.94，P=0.028）。此外，TNBC 中 CCNB1 与 CDK1 之间以及 CCNA2 与 CDK1 之间存在相关性（r=0.804，P<0.001；r=0.577，P<0.001）。
本研究结果表明，细胞周期蛋白 CDK1、CCNB1 和 CCNA2 在 TNBC 中过度表达，可作为 TNBC 诊断和治疗的新型生物标志物。
