Prognostic Correlation Between MFG-E8 Expression Level and Colorectal Cancer

被引:20
作者
Jia, Min [1 ]
Yao, Huaning [2 ]
Chen, Chao [1 ]
Wang, Yueqin [1 ]
Wang, Han [1 ]
Cui, Tianpen [1 ]
Zhu, Jianhua [1 ]
机构
[1] HUST, Tongji Med Coll, Lab Clin Immunol, Wuhan Hosp 1, 215 Zhongshan Dadao, Wuhan 430022, Hubei, Peoples R China
[2] HUST, Tongji Med Coll, Dept Pathol, Wuhan Hosp 1, Wuhan, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
CRC; MFG-E8; Tissue microarray; Immunohistochemistry; Prognosis; GROWTH-FACTOR; 8; APOPTOTIC CELLS; MALIGNANT-MELANOMA; GENE-EXPRESSION; FACTOR-VIII; ANGIOGENESIS; CARCINOGENESIS; PROGRESSION; CARCINOMA; LESIONS;
D O I
10.1016/j.arcmed.2017.06.003
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background and Aims. Colorectal cancer (CRC) is one of the leading causes of cancer related death all over the world. Milk fat globule-epidermal growth factor (EGF)-factor VIII (MFG-E8) was found to be highly expressed in a variety of cancers. However its role in CRC is unclear. This study investigates the expression of MFG-E8 in CRC tissues and the correlation with clinicopathological features and prognosis in CRC patients. Methods. The expression of MFG-E8 proteins was detected by immunohistochemical staining in 90 samples of CRC. The localization of MFG-E8 in colorectal tumor was examined by immunofluorescence staining The correlation between MFG-E8 protein expression and the clinical pathological features of CRC were evaluated by chi(2) test and Fisher's exact test. The survival rates were analyzed by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was analyzed by the Cox proportional hazard models. Results. Our results showed that MFG-E8 expression increased significantly in colorectal cancer compared with normal mucosa tissues (p <0.001). We further validated MFG-E8 overexpression in 6 pairs of fresh tumor and adjacent normal mucosa tissues from colorectal cancer patients by Western blot (p <0.05). Immunofluorescence staining showed that MFG-E8 accumulated in close proximity to endothelial cells in human colorectal tumor tissue. In addition, high MFG-E8 protein expression was correlated with lymph node metastasis and some pathological classifications (p <0.05). Furthermore, patients with high protein level of MFG-E8 showed shortened overall survivals (p <0.05). Conclusion. Our results showed that MFG-E8 could be a potential novel prognostic marker for CRC and overexpression of MFG-E8 might be involved in lymph node metastasis and angiogenesis of CRC. (C) 2017 IMSS. Published by Elsevier Inc.
引用
收藏
页码:270 / 275
页数:6
相关论文
共 26 条
[11]   MFG-E8-mediated uptake of apoptotic cells by APCs links the pro- and antiinflammatory activities of GM-CSF [J].
Jinushi, Masahisa ;
Nakazaki, Yukoh ;
Dougan, Michael ;
Carrasco, Daniel R. ;
Mihm, Martin ;
Dranoff, Glenn .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (07) :1902-1913
[12]   Milk fat globule epidermal growth factor-8 blockade triggers tumor destruction through coordinated cell-autonomous and immune-mediated mechanisms [J].
Jinushi, Masahisa ;
Sato, Marimo ;
Kanamoto, Akira ;
Itoh, Akihiko ;
Nagai, Shigenori ;
Koyasu, Shigeo ;
Dranoff, Glenn ;
Tahara, Hideaki .
JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (06) :1317-1326
[13]   Role of milk fat globule-epidermal growth factor 8 in colonic inflammation and carcinogenesis [J].
Kusunoki, Ryusaku ;
Ishihara, Shunji ;
Tada, Yasumasa ;
Oka, Akihiko ;
Sonoyama, Hiroki ;
Fukuba, Nobuhiko ;
Oshima, Naoki ;
Moriyama, Ichiro ;
Yuki, Takafumi ;
Kawashima, Kousaku ;
Ansary, Md. Mesbah Uddin ;
Tajima, Yoshitsugu ;
Maruyama, Riruke ;
Nabika, Toru ;
Kinoshita, Yoshikazu .
JOURNAL OF GASTROENTEROLOGY, 2015, 50 (08) :862-875
[14]  
McMillan DC, 2007, SURG ONCOL, V16, P3, DOI 10.1016/j.suronc.2007.04.008
[15]   Potentiation of Platelet-Derived Growth Factor Receptor-β Signaling Mediated by Integrin-Associated MFG-E8 [J].
Motegi, Sei-ichiro ;
Garfield, Susan ;
Feng, Xu ;
Sardy, Miklos ;
Udey, Mark C. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2011, 31 (11) :2653-U747
[16]   MFG-E8/lactadherin promotes tumor growth in an angiogenesis-dependent transgenic mouse model of multistage carcinogenesis [J].
Neutzner, Melanie ;
Lopez, Theresa ;
Feng, Xu ;
Bergmann-Leitner, Elke S. ;
Leitner, Wolfgancr W. ;
Udey, Mark C. .
CANCER RESEARCH, 2007, 67 (14) :6777-6785
[17]   Expression of milk fat globule epidermal growth factor-VIII may be an indicator of poor prognosis in malignant melanoma [J].
Oba, J. ;
Moroi, Y. ;
Nakahara, T. ;
Abe, T. ;
Hagihara, A. ;
Furue, M. .
BRITISH JOURNAL OF DERMATOLOGY, 2011, 165 (03) :506-512
[18]   Milk fat globule-epidermal growth factor-factor VIII (MFGE8)/lactadherin promotes bladder tumor development [J].
Sugano, G. ;
Bernard-Pierrot, I. ;
Lae, M. ;
Battail, C. ;
Allory, Y. ;
Stransky, N. ;
Krumeich, S. ;
Lepage, M-L ;
Maille, P. ;
Donnadieu, M-H ;
Abbou, C. C. ;
Benhamou, S. ;
Lebret, T. ;
Sastre-Garau, X. ;
Amigorena, S. ;
Radvanyi, F. ;
Thery, C. .
ONCOGENE, 2011, 30 (06) :642-653
[19]   Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain [J].
Sun, LX ;
Hui, AM ;
Su, Q ;
Vortmeyer, A ;
Kotliarov, Y ;
Pastorino, S ;
Passaniti, A ;
Menon, J ;
Walling, J ;
Bailey, R ;
Rosenblum, M ;
Mikkelsen, T ;
Fine, HA .
CANCER CELL, 2006, 9 (04) :287-300
[20]   Novel genes associated with malignant melanoma but not benign melanocytic lesions [J].
Talantov, D ;
Mazumder, A ;
Yu, JX ;
Briggs, T ;
Jiang, YQ ;
Backus, J ;
Atkins, D ;
Wang, YX .
CLINICAL CANCER RESEARCH, 2005, 11 (20) :7234-7242