Lifeng Yu1, Lin Zhao1, Zhen Jia1, Jia Bi1, Qian Wei1, Xinyue Song1, Longyang Jiang1, Shu Lin1, Minjie Wei2. 1. Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, 110122, China; 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. 2. Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, 110122, China; 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. Electronic address: weiminjiecmu@163.com.
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.
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 humanbreast 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 cancerpatients 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.
Authors: Dragana Kopanja; Vaibhav Chand; Eilidh O'Brien; Nishit K Mukhopadhyay; Maria P Zappia; Abul B M M K Islam; Maxim V Frolov; Bradley J Merrill; Pradip Raychaudhuri Journal: Cancer Res Date: 2022-07-05 Impact factor: 13.312
Authors: Sanni E Ruotsalainen; Ida Surakka; Nina Mars; Juha Karjalainen; Mitja Kurki; Masahiro Kanai; Kristi Krebs; Sarah Graham; Pashupati P Mishra; Binisha H Mishra; Juha Sinisalo; Priit Palta; Terho Lehtimäki; Olli Raitakari; Lili Milani; Yukinori Okada; Aarno Palotie; Elisabeth Widen; Mark J Daly; Samuli Ripatti Journal: Commun Biol Date: 2022-08-17