Identification of Key Genes and Pathways Associated With Irradiation in Breast Cancer Tissue and Breast Cancer Cell Lines

Dose Response. 2020 Jun 18;18(2):1559325820931252. doi: 10.1177/1559325820931252. eCollection 2020 Apr-Jun.

Abstract

Radiotherapy is mainly a traditional treatment for breast cancer; however, the key genes and pathways in breast cancer associated with irradiation are not clear. In this study, we aimed to explore the messenger RNA expression changes between preradiation and postradiation breast cancer. The gene expression data set (GSE59733) was downloaded from Gene Expression Omnibus database. According to |log2FC (fold change) | ≥ 1 and with false discovery rate adjusted P value <.05, differentially expressed genes (DEGs) were screened and annotated by R programming software. The protein-protein interaction (PPI) network was conducted through STRING database, and subnetworks and hub genes were extracted by plug-in in Cytoscape. A total of 82 DEGs (74 upregulated and 8 downregulated genes) were identified. These DEGs mainly enriched in an intrinsic apoptotic signaling pathway and G-protein-coupled receptor binding. What's more, tumor necrosis factor signaling pathway and interleukin 17 signaling pathway abnormally activated in postradiation tumor samples. Two characteristic subnetworks and 3 hub genes (FOS, CCL2, and CXCL12) were strongly distinguished in PPI network. Moreover, the expression level of the hub genes was confirmed in irradiated MCF-7 cell and SUM-159 cell using quantitative real-time polymerase chain reaction assay. These findings imply that these hub genes may play momentous function in breast cancer to irradiation.

Keywords: DEGs; GEO database; bioinformatics; breast cancer; radiotherapy.