Identification of PLK4 as a key prognostic gene in breast cancer by bioinformatics analysis

  Objective  To explore the biological role and prognostic value of Polo-like kinase 4 (PLK4) in breast cancer and its influence on local immune microenvironment by bioinformatics analysis.

  Methods  The expression levels of PLK4 in a variety of tumors were mined through the Oncomine database. The differences in PLK4 expression in breast cancer tissues and normal tissues were retrieved by the GEPIA database and the HPA database. The correlations between PLK4 expression levels and clinical characters as well as immune infiltration in breast cancer patients were analyzed by the UALCAN database and the TIMER database respectively. The K-M plotter database was used to evaluate the prognostic value of PLK4 in breast cancer. Coexpedia database was used to construct the co-expressed gene network of PLK4 in breast cancer, and the functions of PLK4 and its key genes were analyzed by David database.

  Results  Both PLK4 mRNA and protein expression were significantly up-regulated in breast cancer tissues, especially in differences of P53 mutant and triple-negative breast cancers (P < 0.05), and high PLK4 expression indicated a worse prognosis. PLK4 was positively correlated with immune cell expression in the immune microenvironment of breast cancer. Twenty-five key genes of PLK4 were screened, including TPX2, CCNB2, CCNB1, BIRC5, CDC20, FOXM1 and etc, and their biological functions were mainly correlated with cell division, cell cycle, cell proliferation, ubiquitination modification and etc. KEGG pathway enrichment analysis showed that PLK4 was associated with P53 signaling pathway, FoxO signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, etc.

  Conclusion  The high expression of PLK4 in breast cancer tissues may indicate a poor prognosis, and it affects the immune microenvironment of breast cancer and shows the characteristics of oncogenes to a certain extent, so it might be used as a predictive indicator for the treatment of breast cancer, and is expected to become a new target for clinical diagnosis and treatment for breast cancer.