【摘要】 目的 通过分析癌症基因组图谱（the cancer genome atlas,TCGA）数据库构建三阴性乳腺癌（triple negative breast cancer,TNBC）预后相关的竞争性内源性核糖核酸（competitive endogenous RNA, ceRNA）调控网络。方法 从TCGA数据库中下载TNBC lncRNA表达RNAseq数据，对TNBC患者的mRNA,miRNA和lncRNA进行差异表达分析，并进一步行生存分析，得到与乳腺癌有明显差异表达同时也对生存有相关性的mRNA,miRNA和lncRNA。同时构建lncRNA-miRNA-mRNA相关ceRNA调控网，再对生存相关lncRNA所相关的mRNA进一步功能富集和注释，并构建蛋白质互作网络最终用关键基因通过人类蛋白质图谱（the human protein atlas,HPA）数据库进行验证。结果在TCGA中共找到TNBC差异表达mRNA 2 331个、差异miRNA 100个和差异lncRNA 1 269个。ceRNA调控网中的mRNA在细胞黏附、唾液分泌和血小板活化、用于IgA产生的肠道免疫网络、补体和凝血级联反应等信号通路中明显富集。生存分析中，1个差异mRNA(NMUR1),1个差异表达miRNA(hsa-miR-6832-3p),2个差异表达的lncRNA(AC104809,LINC01297)的表达量均与TNBC患者的预后相关，差异具有统计学意义（P <0.05）。最后利用HPA数据库对NMUR1蛋白水平和生存分析验证，NMUR1的高表达患者的总生存期显著高于NMUR1低表达组，差异有统计学意义（P <0.05）。结论 成功构建了促进TNBC发生发展的lncRNA-miRNA-mRNA调控网络，筛选得到生存相关的差异mRNA,miRNA和lncRNA为TNBC发病机制的研究和诊疗生物标志物的探索提供参考依据。更多还原

【Abstract】 Objective By analyzing the cancer genome atlas(TCGA) database, a competitive endogenous RNA(ceRNA)regulatory network related to the prognosis of triple negative breast cancer(TNBC) was constructed. Methods Download TNBC lncRNA expression RNAseq data from the TCGA database, analyzed the differential expression of mRNA, miRNA and lncRNA in TNBC patients, and further conduct survival analysis to obtain mRNA, miRNA and lncRNA that have significant differential expression with breast cancer and were also relevant to survival. At the same time, the lncRNA-miRNA-mRNA related ceRNA regulatory network was constructed, and then the mRNA related to survival related lncRNA was further enriched and annotated, and the protein interaction network was constructed. Finally, the key genes were verified by the human protein atlas(HPA) database. Results 2 331 differentially expressed mRNA, 100 differentially expressed miRNA and 1 269differentially expressed lncRNA were found in TCGA in triple negative breast cancer. The mRNA in the ceRNA regulatory network was significantly enriched in signal pathways such as cell adhesion, salivary network for IgA production, complement and coagulation cascade immune, platelet activation, intestinal in survival analysis, the expression of 1 differential mRNA(NMUR1), 1 differential expression miRNA(hsa-miR-6832-3p), and 2 differential expression lncRNAs(AC104809,LINC01297)were all related to the prognosis of TNBC patients, and the difference was statistically significant(P < 0.05).Finally, the analysis of NMUR1 protein level and survival using HPA database verified that the overall survival of patients with high NMUR1expression was significantly higher than that of patients with low NMUR1 expression, and the difference was statistically significant(P < 0.05). Conclusion The lncRNA-miRNA-mRNA regulatory network promoting the occurrence and development of TNBC has been successfully constructed, and the survival related differential mRNA, miRNA and lncRNA have been screened, providing a reference for the study of the pathogenesis of triple negative breast cancer and the exploration of biomarkers for diagnosis and treatment.更多还原