Mitochondria-Related Core Genes in Breast Cancer: Potential Diagnostic, Prognostic Markers and Therapeutic Targets

Abstract Background: Mitochondria-nuclear cross talk and mitochondrial retrograde regulation are involved in the genesis and development of breast cancer (BC). Therefore, mitochondria can be regarded as a promising target for BC therapeutic strategies. In the present study, we aimed to seek the potential biomarkers of BC diagnosis and prognosis and also the molecular therapeutic targets from the perspective of mitochondrial dysfunction.Methods: The microarray data of mitochondria-related encoding genes of BC were downloaded from GEO including GSE128610 and GSE72319. GSE128610 was treated as test set and validation sets consisted of GSE72319 and TCGA, which were used for identifying mitochondria-related differential expressed genes (mrDEGs). GO analysis and KEGG mapping of validated mrDEGs was performed by STRING and KEGG mapper, respectively. PPI network was constructed by STRING. MCODE was applied to modeling prediction of PPI and hub mrDEGs were screened by cytohubba. The online tool of Kaplan Meier plotter was adopted to analyze the correlation between hub mrDEGs and the overall survival of BC patients.Results: A total of 23 up-regulated and 71 down-regulated mrDEGs were identified and validated. Enrichment analyses indicated that mrDEGs were associated with several biological processes, including cell migration, cell surface receptor signaling pathway, cell differentiation and cell communication. Meanwhile, these genes were mapped in PI3K-ALT pathway, TGF-beta pathway, evading apoptosis pathway and resistance to chemotherapy pathway. Moreover, 9 hub mrDEGs were identified. Among them, up-regulated hub mrDEGs contained FN1, BGN, EFNA3, COL5A2 and SEMA3F, and down-regulated hub mrDEGs comprised RHOQ, SEMA3A, NRP1 and DDR2. Overall survival analysis suggested that the up-regulated FN1 and SEMA3F and down-regulated DDR2 conferred to poor BC prognosis.Conclusion: The 9 hub mrDEGs, especially FN1, SEMA3F and DDR2, were likely to regulate mitochondrial function and might be novel biomarkers of BC diagnosis and prognosis as well as the therapeutic targets.