EYA2 Correlates With Clinico-Pathological Features of Breast Cancer, Promotes Tumor Proliferation, and Predicts Poor Survival

Eyes absent homolog 2 (EYA2), a transcriptional activator, is pivotal for organ development, but aberrant regulation of EYA2 has been reported in multiple human tumors. However, the role of EYA2 in breast cancer is still lack of full understanding. To explore the biological significance of EYA2 in breast cancer, we conducted data analysis on public breast cancer datasets, and performed immunohistochemistry (IHC) analysis, colony-forming unit assays, EdU assay, western blotting, and immunofluorescence (IF). Meta-analysis showed that EYA2 mRNA expression was correlated with tumor grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). IHC analysis displayed that EYA2 protein abundance was inversely associated with the status of ER and PR, and enriched in triple-negative breast cancer in comparison with luminal-type tumors. Additionally, correlation analysis reflected that EYA2 mRNA was negatively correlated with luminal markers, and positively associated with markers of basal cells, epithelial-mesenchymal transition and cancer stem cells. Clone-forming assay and EdU experiment showed that EYA2 overexpression enhanced proliferation of breast cancer cells. Results from western blotting and IF displayed that overexpression of EYA2 up-regulated the protein abundance of proliferation markers. Importantly, survival analysis indicated that higher EYA2 mRNA level predicted worse overall survival, relapse-free survival and metastasis-free survival among whole enrolled breast cancer patients. Collectively, EYA2 was closely correlated with clinico-pathological characteristics, and served as a proliferation stimulator for breast cancer cells and an unfavorable prognostic element for breast cancer patients, suggesting that EYA2 is involved in the progression of breast carcinoma.