MFG-E8 overexpression is associated with poor prognosis in breast cancer patients

Background: MFG-E8(Milk fat globule-EGF factor 8), a secreted glycoprotein, plays an exceptional role in various diseases. MFG-E8 overexpression is found in a variety of cancers. However, it remains unclear whether MFG-E8 overexpression is associated with the clinicopathological characteristics and prognosis of human breast cancer. Materials and methods: In this study, we detected the expression and localization of MFG-E8 protein in breast cancer and cancer-adjacent tissues using immunohistochemical staining, Western blot analysis and immuno-fluorescence. We analyzed the association between MFG-E8 expression and clinical characteristics and outcomes of breast cancer patients with different HR and HER2 statuses. Results: Our results confirmed that MFG-E8 expression increased significantly in breast cancer compared with cancer-adjacent tissues by immunohistochemical staining (P < 0.001). Similarly, the Western blot results further confirmed the increased expression of MFG-E8 in breast cancer compared with cancer-adjacent tissues (P = 0.001). Immunofluorescence staining showed that MFG-E8 was mainly localized in the cytoplasm and membrane of tumor cells, consistent with the immunohistochemical staining results. The high expression levels of MFG-E8 showed a greater association with lymph node metastasis, TNM stage and histological grade (P < 0.001). Moreover, high MFG-E8 expression was related to a shortened overall survival (OS) (P < 0.001) and disease-free survival (DFS) (P < 0.001). Bioinformatics analysis with a Kaplan-Meier plotter also demonstrated a strong association of MFG-E8 mRNA overexpression with a short OS and DFS compared with low MFG-E8 expression (P = 0.040, P = 0.005). Conclusions: Our findings indicate that MFG-E8 may be a potential marker for poor prognosis and survival in breast cancer.