Department of Laboratory Medicine, Shying People's Hospital, Shying, Jiangsu 223600, P.R. China.
Department of Internal Medicine, Mercer University School of Medicine, Macon, GA 31201, USA.
Oncol Rep. 2018 Jun;39(6):2865-2872. doi: 10.3892/or.2018.6393. Epub 2018 Apr 23.
Breast carcinoma is one of the most common types of malignant neoplasms, and is associated with high rates of morbidity and mortality. Altered gene expression is critical in the development of breast cancer. To identify the important differentially expressed genes and microRNAs in breast carcinoma, mRNA (GSE26910, GSE42568, and GSE89116) and microRNA (GSE35412) microarray datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed microRNA expression data were extracted with GEO2R online software. The DAVID online database was used to perform a function and pathway enrichment analysis of the key identified differentially expressed genes. A protein-protein interaction (PPI) network was constructed using the STRING online database, and visualized in Cytoscape software. The effect of the expression level of the key identified genes on overall survival (OS) time was analyzed by using the Kaplan-Meier Plotter online database. Furthermore, the online miRNA databases TargetScan, microT-CDS, and TarBase were used to identify the target genes of the differentially expressed miRNAs. A total of 254 differentially expressed genes were identified, which were enriched in cell adhesion, polysaccharide binding, extracellular region part and ECM-receptor interactions. The PPI network contained 250 nodes and 375 edges. Five differentially expressed genes were found to be significantly negatively correlated with the differentially expressed miRNAs, which were potentially also target genes for miRNAs. Four of the five genes, including AKAP12, SOPB, TCF7L2, COL12A1 and TXNIP were downregulated, and were associated with the OS of patients with breast carcinoma. In addition, a total of 130 differentially expressed miRNAs were identified. In conclusion, these results constitute a novel model for miRNA-mRNA differential expression patterns, and further studies may provide potential targets for diagnosing and understanding the mechanisms of breast carcinoma.
乳腺癌是最常见的恶性肿瘤之一,其发病率和死亡率都很高。基因表达的改变在乳腺癌的发生发展中起着至关重要的作用。为了鉴定乳腺癌中重要的差异表达基因和 microRNA,从基因表达综合数据库中下载了 mRNA(GSE26910、GSE42568 和 GSE89116)和 microRNA(GSE35412)微阵列数据集。使用 GEO2R 在线软件提取差异表达 microRNA 表达数据。使用 DAVID 在线数据库对关键鉴定的差异表达基因进行功能和通路富集分析。使用 STRING 在线数据库构建蛋白质-蛋白质相互作用(PPI)网络,并在 Cytoscape 软件中可视化。使用 Kaplan-Meier Plotter 在线数据库分析关键鉴定基因的表达水平对总生存期(OS)时间的影响。此外,使用在线 microRNA 数据库 TargetScan、microT-CDS 和 TarBase 来鉴定差异表达 microRNA 的靶基因。共鉴定出 254 个差异表达基因,这些基因富集在细胞黏附、多糖结合、细胞外区域部分和 ECM-受体相互作用。PPI 网络包含 250 个节点和 375 个边。发现 5 个差异表达基因与差异表达 microRNA 显著负相关,这些基因可能也是 microRNA 的靶基因。这 5 个基因中,有 4 个(AKAP12、SOPB、TCF7L2、COL12A1 和 TXNIP)下调,与乳腺癌患者的 OS 相关。此外,还鉴定出 130 个差异表达 microRNA。总之,这些结果构成了 miRNA-mRNA 差异表达模式的新模型,进一步的研究可能为诊断和理解乳腺癌的机制提供潜在的靶点。