Gao Guangyu, Shi Xinya, Yao Zhen, Shen Jiaofeng, Shen Liqin
Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China.
Medicine (Baltimore). 2020 Sep 25;99(39):e22105. doi: 10.1097/MD.0000000000022105.
Lymph node metastasis is a significant problem in breast cancer, and its underlying molecular mechanism is still unclear. The purpose of this study is to research the molecular mechanism and to explore the key RNAs and pathways that mediate lymph node metastasis in breast cancer.
GSE100453 and GSE38167 were downloaded from the Gene Expression Omnibus (GEO) database and 569 breast cancer statistics were also downloaded from the TCGA database. Differentially expressed miRNAs were calculated by using R software and GEO2R. Gene ontology and Enriched pathway analysis of target mRNAs were analyzed by using the Database for Database of Annotation Visualization and Integrated Discovery (DAVID) and R software. The protein-protein interaction (PPI) network was performed according to Metascape, String, and Cytoscape software.
In total, 6 differentially expressed miRNAs were selected, and 499 mRNAs were identified after filtering. The research of the Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated that mRNAs enriched in certain tumor pathways. Also, certain hub mRNAs were highlighted after constructed and analyzed the PPI network. A total of 3 out of 6 miRNAs had a significant relationship with the overall survival (P < .05) and showed a good ability of risk prediction model of over survival.
By utilizing bioinformatics analyses, differently expressed miRNAs were identified and constructed a complete gene network. Several potential mechanisms and therapeutic and prognostic targets of lymph node metastasis were also demonstrated in breast cancer.
淋巴结转移是乳腺癌中的一个重要问题,其潜在的分子机制仍不清楚。本研究的目的是研究分子机制,并探索介导乳腺癌淋巴结转移的关键RNA和信号通路。
从基因表达综合数据库(GEO)下载GSE100453和GSE38167数据集,并从TCGA数据库下载569例乳腺癌统计数据。使用R软件和GEO2R计算差异表达的miRNA。使用注释可视化与综合发现数据库(DAVID)和R软件对靶mRNA进行基因本体论和富集通路分析。根据Metascape、String和Cytoscape软件构建蛋白质-蛋白质相互作用(PPI)网络。
总共筛选出6个差异表达的miRNA,经过筛选后鉴定出499个mRNA。京都基因与基因组百科全书(KEGG)研究表明,mRNA在某些肿瘤通路中富集。此外,构建并分析PPI网络后突出显示了某些关键mRNA。6个miRNA中有3个与总生存期显著相关(P<0.05),并显示出良好的总生存期风险预测模型能力。
通过生物信息学分析,鉴定出差异表达的miRNA并构建了完整的基因网络。还阐明了乳腺癌淋巴结转移的几种潜在机制以及治疗和预后靶点。