High expression of polo-like kinase 1 is associated with TP53 inactivation, DNA repair deficiency, and worse prognosis in ER positive Her2 negative breast cancer.

Polo-like kinase 1 (PLK1), the most investigated member of the PLK family, plays a pivotal role both in the p53-mediated regulation of DNA damage repair and in mitosis, especially in the G2/M phase. However, the evidence on the clinical and prognostic relevance of PLK1 is limited to triple negative subtype among breast cancer (BC). We hypothesized that high expression of PLK1 is associated with TP53 inactivation, DNA repair deficiency, and worse prognosis in ER positive in BC in a large-scale cohort should clarify its clinical relevance for each BC subtype. Total of 3173 BC cases; 1025 from TCGA cohort, 1904 from METABRIC, and 244 from neoadjuvant chemotherapy (NAC) cohort from Gene Expression Omnibus dataset, GSE32603, were analyzed. PLK1 expressions were significantly higher in high Nottingham Grade and triple negative BC. High expression of PLK1 was significantly associated with TP53 mutation, high expression of TP53 mRNA as well as protein, and it significantly correlated with the homologous recombination deficiency score. High PLK1 expression significantly enriched cell cycle related gene sets (G2/M check point, E2F targets), MTORC1 signaling and MYC target gene sets in the Gene Set Enrichment Analysis. High expression of PLK1 was significantly associated with tumor infiltrating lymphocytes and tumor associated macrophages (high levels of CD8+ T cells, M0 and M1 macrophage, and low levels of M2 macrophage), and high immune cytolytic activity. While high expression of PLK1 did not associate with pathological complete response after NAC, it was associated with poor prognosis in the whole cohort and in the ER-positive/HER2-negative subtype of TCGA. High expression of PLK1 is significantly associated with TP53 mutations, DNA repair deficiency and worse prognosis in BC particularly in HR+HER2- subtype. Using bioinformatics methods with large cohorts.