Xiao Xiao, Zhang Zheng, Luo Ruihan, Peng Rui, Sun Yan, Wang Jia, Chen Xin
Department of Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
Oncol Lett. 2021 May;21(5):363. doi: 10.3892/ol.2021.12624. Epub 2021 Mar 10.
Triple-negative breast cancer (TNBC) is a subtype with high rates of metastasis, poor prognosis and limited therapeutic options. The present study aimed to identify the potential pivotal genes for prognosis and treatment in TNBC. A total of two microarray expression datasets, GSE38959 and GSE65212, were downloaded from the Gene Expression Omnibus database, and RNA-sequencing data of breast cancer from The Cancer Genome Atlas database were analyzed to screen out differentially expressed genes (DEGs) between TNBC tissues and normal tissues. The intersection of DEGs was submitted to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. A protein-protein interaction (PPI) network was constructed and visualized using Cytoscape software. Furthermore, module, centrality and survival analyses were performed to identify the potential hub genes. Reverse transcription-quantitative (RT-q)PCR analysis was performed to detect the expression levels of key genes in TNBC samples, and 377 DEGs were identified. Functional analysis revealed that the DEGs were significantly involved in cell cycle process, nuclear division and the p53 signaling pathway. A PPI network was constructed with these DEGs, and 66 core genes with high centrality features in module 1 were selected. Relapse-free survival analysis confirmed that high expression levels of five genes [cyclin B1 (CCNB1), GINS complex subunit 2, non-SMC condensin I complex subunit G (NCAPG), minichromosome maintenance 4 (MCM4) and ribonucleotide reductase regulatory subunit M2 (RRM2)] were significantly associated with poor prognosis in TNBC. RT-qPCR analysis demonstrated that CCNB1, NCAPG, MCM4 and RRM2 were significantly upregulated in 25 TNBC tissues compared with adjacent normal breast tissues. Furthermore, gene set enrichment analysis revealed that CCNB1, NCAPG, MCM4 and RRM2 were closely associated with tumor proliferation. Taken together, these results suggest that CCNB1, NCAPG, MCM4 and RRM2 are associated with tumorigenesis and TNBC progression, and thus may act as promising prognostic biomarkers and therapeutic targets for TNBC.
三阴性乳腺癌（TNBC）是一种转移率高、预后差且治疗选择有限的亚型。本研究旨在确定TNBC中预后和治疗的潜在关键基因。从基因表达综合数据库下载了两个微阵列表达数据集GSE38959和GSE65212，并分析了来自癌症基因组图谱数据库的乳腺癌RNA测序数据，以筛选出TNBC组织和正常组织之间的差异表达基因（DEG）。将DEG的交集提交给基因本体论和京都基因与基因组百科全书富集分析。使用Cytoscape软件构建并可视化蛋白质-蛋白质相互作用（PPI）网络。此外，进行了模块、中心性和生存分析以识别潜在的枢纽基因。进行逆转录定量（RT-q）PCR分析以检测TNBC样本中关键基因的表达水平，共鉴定出377个DEG。功能分析表明，这些DEG显著参与细胞周期进程、核分裂和p53信号通路。用这些DEG构建了一个PPI网络，并选择了模块1中具有高中心性特征的66个核心基因。无复发生存分析证实，五个基因[细胞周期蛋白B1（CCNB1）、GINS复合体亚基2、非SMC凝聚素I复合体亚基G（NCAPG）、微小染色体维持蛋白4（MCM4）和核糖核苷酸还原酶调节亚基M2（RRM2）]的高表达水平与TNBC的不良预后显著相关。RT-qPCR分析表明，与相邻正常乳腺组织相比，25个TNBC组织中CCNB1、NCAPG、MCM4和RRM2显著上调。此外，基因集富集分析表明，CCNB1、NCAPG、MCM4和RRM2与肿瘤增殖密切相关。综上所述，这些结果表明CCNB1、NCAPG、MCM4和RRM2与肿瘤发生和TNBC进展相关，因此可能作为TNBC有前景的预后生物标志物和治疗靶点。
