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MFG-E8 overexpression is associated with poor prognosis in breast cancer patients
Authors:Lifeng Yu  Lin Zhao  Zhen Jia  Jia Bi  Qian Wei  Xinyue Song  Longyang Jiang  Shu Lin  Minjie Wei
Institution:1. Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, 110122, China;2. Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
Abstract:

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 immunofluorescence. 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.
Keywords:OS  overallsurvival  DFS  disease-free survival  MFG-E8  milk fat globule-EGF factor 8  ER  estrogen receptor  PR  progesterone receptor  HR  hormone receptor  HER2  human epidermal growth factor receptor-2  MFG-E8  Breast cancer  Clinicopathological characteristics  Prognosis
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