Clinical implications of Ezrin and CD44 co-expression in breast cancer

The aim of the present study was to investigate the expression status and clinical implications of the stem cell genes Ezrin and CD44 in breast cancers. Expression of the Ezrin protein in CD44+/CD24(-/low) tumor cells (CSCs) was detected by western blotting. The resulting expression status and the relationship between Ezrin and CD44 were determined in 726 breast cancers using immunohistochemistry staining and immunofluorescence double staining. Subsequently, the relationship between Ezrin and CD44 protein co-expression and clinicopathological parameters and prognosis was determined. The Ezrin protein was expressed at a higher level in CSCs when compared to that in the control cells and was related to the resistance of CSCs to chemotherapy. The Ezrin and CD44 proteins were co-expressed in the co-immunoprecipitation (Co-IP) test. Ezrin and CD44 co-expression was observed in 235 (32.37%) of the 726 cases examined. After universal analysis and multivariate analysis, histological type, lymph node metastasis, triple-negative breast cancer, TNM stage and distant metastasis were verified as related to Ezrin and CD44 co-expression (P = 0.011, 0.006, 0.001, 0.011 and 0.001, respectively). A survival analysis revealed that Ezrin and CD44 co-expression was associated with a poorer prognosis (36.91 vs. 81.54%, P = 0.001). After running Cox regression, the factors of age, tumor size, lymph node metastasis, triple-negative tumor status, TNM stage, distant metastasis and Ezrin and CD44 co-expression were shown to be independent prognostic factors of breast cancer. The co-expression of Ezrin and CD44 may be a new biomarker for evaluating the progression and chemotherapy sensitivity of breast cancer.