Departments of Breast Surgery, The First Hospital of China Medical University, Shenyang, 110001, People's Republic of China.
Invest New Drugs. 2021 Jun;39(3):705-712. doi: 10.1007/s10637-020-01059-1. Epub 2021 Jan 4.
Breast cancer threatens women's health. Although there are a lot of methods to treat breast cancer, chemotherapy resistance still hinders the effectiveness of treatment. This study attempts to explore the mechanism of chemotherapy resistance from the perspective of miRNA and look for several new targets for developing new drugs. Three datasets (GSE73736, GSE71142 and GSE6434) from Gene Expression Omnibus (GEO) were used for the bioinformatics analysis. Differentially expressed miRNAs (DE-miRNAs) and differentially expressed genes (DE-genes) were obtained by using R package "limma". DAVID tool was used to perform gene ontology annotation analysis (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the overlapping genes. Protein-protein interaction (PPI) network was established by STRING database and visualized by software Cytoscape. Hub genes were identified by software Cytoscape. The prognostic value of hub genes was assessed through Kaplan-Meier plotter website. In total, 22 DE-miRNAs, 1932 DE-genes and top 10 hub genes were obtained. The genes were mainly enriched in cell signaling pathways like ErbB signaling pathway and PI3K / AKT/mTOR pathway. These pathways have a significant impact on the proliferation, invasion and drug resistance in cancer. MiRNA-Gene interaction may provide new insight for exploring the mechanism of chemotherapy resistance in breast cancer. Our study ultimately identified effective biomarkers and potential drug targets, which may enhance the effect of chemotherapy in patients with breast cancer.
乳腺癌威胁着女性的健康。尽管有很多方法可以治疗乳腺癌,但化疗耐药性仍然阻碍了治疗的效果。本研究试图从 miRNA 的角度探索化疗耐药的机制,并寻找一些新的药物开发靶点。本研究从基因表达综合数据库(GEO)中选取了三个数据集(GSE73736、GSE71142 和 GSE6434)进行生物信息学分析。使用 R 包“limma”获得差异表达 miRNA(DE-miRNA)和差异表达基因(DE-gene)。使用 DAVID 工具对重叠基因进行基因本体论注释分析(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。通过 STRING 数据库建立蛋白质-蛋白质相互作用(PPI)网络,并使用 Cytoscape 软件进行可视化。使用 Cytoscape 软件识别枢纽基因。通过 Kaplan-Meier plotter 网站评估枢纽基因的预后价值。总共获得了 22 个 DE-miRNA、1932 个 DE-gene 和前 10 个枢纽基因。这些基因主要富集在细胞信号通路中,如 ErbB 信号通路和 PI3K/AKT/mTOR 通路。这些通路对癌症的增殖、侵袭和耐药性有重要影响。miRNA-基因相互作用可能为探索乳腺癌化疗耐药机制提供新的思路。本研究最终确定了有效的生物标志物和潜在的药物靶点,这可能增强乳腺癌患者化疗的效果。