Integrated analysis of expression profiling data identifies three genes in correlation with poor prognosis of triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) shows more aggressive clinical behavior and poorer outcome than non-triple-negative breast cancer (NTNBC), and cannot be treated either via endocrine therapy or by Trastuzumab. For TNBC, chemotherapy is currently the mainstay of systemic medical treatment, the lack of more efficient options of treatment has been a problem in breast cancer prevention. In this study, we aimed to find genes related to prognosis in TNBC by bioinformatic analysis and to provide therapeutic candidates for TNBC treatment. We compared the differences in gene expression levels between cancer patients and healthy individuals across five breast cancer microarray databases to generate a gene cohort specifically upregulated in the NTNBC subtype, whose expression levels are ≥2-fold higher in TNBC compared to NTNBC and healthy individuals. Another two databases with clinical information were applied for following Kaplan-Meier analysis, and high expression of BIRC5, CENPA and FAM64A in this cohort were found to be related to poor survival (OS, DMFS, DFS and RFS). This correlation was also seen in patients at early stages and grades. On the other hand, the outcome of patients with synchronous upregulation of these three genes was the worst, while those with synchronous low gene level was the best. In conclusion, BIRC5, CENPA and FAM64A are specifically upregulated in TNBC, and the high expression of these three genes is associated with poor breast cancer prognosis, suggesting their clinical implication as therapeutic targets in TNBC.