Key Genes and Prognostic Analysis in HER2+ Breast Cancer

Abstract

Human epidermal growth factor 2 (HER2)+ breast cancer is considered the most dangerous type of breast cancers. Herein, we used bioinformatics methods to identify potential key genes in HER2+ breast cancer to enable its diagnosis, treatment, and prognosis prediction. Datasets of HER2+ breast cancer and normal tissue samples retrieved from Gene Expression Omnibus and The Cancer Genome Atlas databases were subjected to analysis for differentially expressed genes using R software. The identified differentially expressed genes were subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses followed by construction of protein-protein interaction networks using the STRING database to identify key genes. The genes were further validated via survival and differential gene expression analyses. We identified 97 upregulated and 106 downregulated genes that were primarily associated with processes such as mitosis, protein kinase activity, cell cycle, and the p53 signaling pathway. Visualization of the protein-protein interaction network identified 10 key genes (<i>CCNA2</i>, <i>CDK1</i>, <i>CDC20</i>, <i>CCNB1</i>, <i>DLGAP5</i>, <i>AURKA</i>, <i>BUB1B</i>, <i>RRM2</i>, <i>TPX2</i>, and <i>MAD2L1</i>), all of which were upregulated. Survival analysis using PROGgeneV2 showed that <i>CDC20</i>, <i>CCNA2</i>, <i>DLGAP5</i>, <i>RRM2</i>, and <i>TPX2</i> are prognosis-related key genes in HER2+ breast cancer. A nomogram showed that high expression of <i>RRM2</i>, <i>DLGAP5</i>, and <i>TPX2</i> was positively associated with the risk of death. <i>TPX2</i>, which has not previously been reported in HER2+ breast cancer, was associated with breast cancer development, progression, and prognosis and is therefore a potential key gene. It is hoped that this study can provide a new method for the diagnosis and treatment of HER2 + breast cancer.