Background: Further elucidation of the molecular mechanisms of the occurrence, development and prognosis of breast cancer remains an urgent need. Identifying hub genes involved in these pathogenesis and progression can potentially help to unveil these mechanisms and provide novel therapeutic targets for breast cancer.
Methods: In this study, we systematically integrated robust rank aggregation (RRA), functional enrichment analysis, protein-protein interaction (PPI) networks construction and analysis, weighted gene co-expression network analysis (WGCNA), DNA methylation analyses and genomic mutation analyses, GSEA and GSVA to identify potential hub genes that are highly associated with breast cancer.
Results: We identified a total of 512 robust DEGs that were significantly associated with breast cancer based on RRA analysis and functional enrichment analysis. CENPL, ISG20L2, MRPL3 and LSM4 were identified as four potential hub genes for breast cancer through the WGCNA analysis and literate search. These four hub genes were upregulated in breast cancer tissues and associated with tumor progression. ROC and Kaplan-Meier indicated these four hub genes all showed good diagnostic performance and prognostic values for breast cancer. Methylation analyses and genomic mutation analyses suggested that the abnormal up-regulation of these genes are likelyresulted from hypomethylation and gene mutations. Moreover, GSEA and GSVA for single potential hub genes revealed they were all tightly related to the proliferation of tumor cells.
Conclusion: We identify four genes (CENPL, ISG20L2, MRPL3, and LSM4) that are likely playing key roles in the molecular mechanism of occurrence and development of breast cancer. They may become potential therapeutic targets for breast cancer patients with further studies. Keywords: breast cancer, RRA, WGCNA, hub genes