Department of Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Department of Bioinformatics, Chongqing Medical University, Chongqing, China.
Biosci Rep. 2021 Jan 29;41(1). doi: 10.1042/BSR20200869.
Triple-negative breast cancer (TNBC) accounts for ∼20% of all breast cancer (BC) cases. The management of TNBC represents a challenge due to its worse prognosis, heterogeneity and lack of targeted therapy. Moreover, its mechanisms are not fully clear. The aim of the study is to identify crucial genes between TNBC and non-TNBC for underlying targets for diagnostic and therapeutic methods of TNBC. The differentially expressed genes (DEGs) between TNBC and non-TNBC were selected from the Gene Expression Omnibus (GEO) database after the integrated analysis of two datasets (GSE65194 and GSE76124). Then Gene ontology (GO) and KEGG analysis were performed by DAVID database, protein-protein interaction (PPI) of DEGs was constructed by Search Tool for the Retrieval of Reciprocity Genes (STRING) database. Furthermore, centrality analysis and module analysis were carried out by Cytoscape to analyze the TNBC-related PPI. Subsequently, overall survival (OS) analysis was performed by GEPIA. Finally, the expressions of these key genes in TNBC and non-TNBC tissues were tested by qRT-PCR. The results showed that 955 DEGs were obtained, which were mainly enriched in ribosome, ribosomal subunit, and so on. Moreover, 19 candidate genes were focused on by centrality analysis and module analysis. Furthermore, we found the low expressions of ribosomal protein S9 (RPS9), ribosomal protein S14 (RPS14), ribosomal protein S27 (RPS27), ribosomal protein L11 (RPL11) and ribosomal protein L14 (RPL14) were related to a poor OS in BC patients. Additionally, qRT-PCR results suggested that these five genes were notably down-regulated in TNBC tissues. In summary, the present study suggests that ribosomal proteins are related to TNBC, and they may play an important role in the diagnosis, treatment and prognosis of TNBC.
三阴性乳腺癌(TNBC)占所有乳腺癌(BC)病例的约 20%。由于其预后较差、异质性和缺乏靶向治疗,TNBC 的治疗极具挑战性。此外,其机制尚不完全清楚。本研究旨在鉴定 TNBC 和非 TNBC 之间的关键基因,为 TNBC 的诊断和治疗方法提供潜在靶点。通过对两个数据集(GSE65194 和 GSE76124)进行综合分析,从基因表达综合数据库(GEO)中选择 TNBC 和非 TNBC 之间的差异表达基因(DEGs)。然后通过 DAVID 数据库进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析,通过 Search Tool for the Retrieval of Reciprocity Genes(STRING)数据库构建 DEGs 的蛋白质-蛋白质相互作用(PPI)。此外,通过 Cytoscape 进行中心性分析和模块分析,分析 TNBC 相关的 PPI。随后,通过 GEPIA 进行总生存(OS)分析。最后,通过 qRT-PCR 检测这些关键基因在 TNBC 和非 TNBC 组织中的表达。结果显示,获得了 955 个 DEGs,这些基因主要富集在核糖体、核糖体亚基等。此外,通过中心性分析和模块分析,重点关注了 19 个候选基因。此外,我们发现核糖体蛋白 S9(RPS9)、核糖体蛋白 S14(RPS14)、核糖体蛋白 S27(RPS27)、核糖体蛋白 L11(RPL11)和核糖体蛋白 L14(RPL14)的低表达与 BC 患者的 OS 不良相关。此外,qRT-PCR 结果表明,这五个基因在 TNBC 组织中明显下调。综上所述,本研究表明核糖体蛋白与 TNBC 相关,它们可能在 TNBC 的诊断、治疗和预后中发挥重要作用。