摘要：Breast cancer is a highly heterogeneous disorder characterized by dysregulation of expression of numerous genes and cascades. In the current study, we aim to use a system biology strategy to identify key genes and signaling pathways in breast cancer. We have retrieved data of two microarray datasets (GSE65194 and GSE45827) from the NCBI Gene Expression Omnibus database. R package was used for identification of differentially expressed genes (DEGs), assessment of gene ontology and pathway enrichment evaluation. The DEGs were integrated to construct a protein–protein interaction network. Next, hub genes were recognized using the Cytoscape software and lncRNA–mRNA co-expression analysis was performed to evaluate the potential roles of lncRNAs. Finally, the clinical importance of the obtained genes was assessed using Kaplan–Meier survival analysis. In the present study, 887 DEGs including 730 upregulated and 157 downregulated DEGs were detected between breast cancer and normal samples. By combining the results of functional analysis, MCODE, CytoNCA and CytoHubba 2 hub genes including MAD2L1 and CCNB1 were selected. We also identified 12 lncRNAs with significant correlation with MAD2L1 and CCNB1 genes. According to The Kaplan–Meier plotter database MAD2L1, CCNA2, RAD51-AS1 and LINC01089 have the most prediction potential among all candidate hub genes. Our study offers a framework for recognition of mRNA–lncRNA network in breast cancer and detection of important pathways that could be used as therapeutic targets in this kind of cancer.
其他摘要：Abstract Breast cancer is a highly heterogeneous disorder characterized by dysregulation of expression of numerous genes and cascades. In the current study, we aim to use a system biology strategy to identify key genes and signaling pathways in breast cancer. We have retrieved data of two microarray datasets (GSE65194 and GSE45827) from the NCBI Gene Expression Omnibus database. R package was used for identification of differentially expressed genes (DEGs), assessment of gene ontology and pathway enrichment evaluation. The DEGs were integrated to construct a protein–protein interaction network. Next, hub genes were recognized using the Cytoscape software and lncRNA–mRNA co-expression analysis was performed to evaluate the potential roles of lncRNAs. Finally, the clinical importance of the obtained genes was assessed using Kaplan–Meier survival analysis. In the present study, 887 DEGs including 730 upregulated and 157 downregulated DEGs were detected between breast cancer and normal samples. By combining the results of functional analysis, MCODE, CytoNCA and CytoHubba 2 hub genes including MAD2L1 and CCNB1 were selected. We also identified 12 lncRNAs with significant correlation with MAD2L1 and CCNB1 genes. According to The Kaplan–Meier plotter database MAD2L1, CCNA2, RAD51-AS1 and LINC01089 have the most prediction potential among all candidate hub genes. Our study offers a framework for recognition of mRNA–lncRNA network in breast cancer and detection of important pathways that could be used as therapeutic targets in this kind of cancer.
