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. 2015 Aug 15;5(9):2777-87.
eCollection 2015.

Lewis Y antigen modified CD47 is an independent risk factor for poor prognosis and promotes early ovarian cancer metastasis

Affiliations

Lewis Y antigen modified CD47 is an independent risk factor for poor prognosis and promotes early ovarian cancer metastasis

Mingzi Tan et al. Am J Cancer Res. .

Abstract

CD47 is a membrane receptor that belongs to the immunoglobulin superfamily and plays an important role in the mechanisms of tumor immune escape. CD47 participates in tumor immune escape by combining with SIRPα to reduce the phagocytic activity of macrophages. There are six potential N-glycosylation sites on CD47, and glycosylation is known to be necessary for its membrane localization. However, it is still unknown to what extent glycosylation influences CD47 ligand binding properties and subsequent signaling. By using immunoprecipitation and confocal laser scanning microscopy, we showed that CD47 contains Lewis y antigen. Immunohistochemical analysis demonstrated that both the positive expression and the overexpression of CD47 and Lewis y antigen in cancer tissues and borderline tumors were significantly higher than those in benign ovarian tumors and normal ovarian tissues (P < 0.05). A linear correlation between the expression patterns of CD47 and Lewis y antigen was evident (r = 0.47, P < 0.01). The high expression of CD47 and Lewis y antigen showed significant correlations with the clinical pathological parameters of ovarian cancer [International Federation of Gynecology and Obstetrics (FIGO) standards, lymph node metastasis, and degree of differentiation] (P < 0.05). The Cox model and Kaplan-Meier tests showed that high expression of CD47 was an independent adverse risk factor for the prognosis of ovarian cancer. Cases with both high CD47 and Lewis y antigen expression had poor prognoses. Our study demonstrates that Lewis y antigens of CD47 may play a crucial role in the development of ovarian cancer, and could be new targets for immunotherapy for ovarian cancer.

Keywords: CD47; Lewis y; ovarian cancer; prognosis; tumor immune escape.

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Figures

Figure 1
Figure 1
Coexpression of CD47 and Lewis y antigens in Ovarian cell lines (CAOV3, SKOV3), IgG is negative control (contained only 10 μl CD47 antibody).
Figure 2
Figure 2
The double-labeling immunofluorescence shows the colocalization of CD47 and Lewis y antigen in ovarian cancer cell line CAOV3 and SKOV3 (original magnification ×400). Nucleus (A1, B1), Lewis y antigen (A2, B2), CD47 (A3, B3) and merged image (A4, B4).
Figure 3
Figure 3
Expression of CD47 and Lewis y antigens in ovarian tissue groups. Immunohistochemical staining in ovarian malignant tumor (A, B), borderline tumor (C, D), benign tumor (E, F), and normal ovarian tissue (G, H). CD47 (A, C, E, G) and Lewis y (B, D, F, H; original magnification ×400).
Figure 4
Figure 4
Kaplan-Meier survival analysis: (A) CD47 and (B) Lewis y antigen expression in ovarian cancer. P value, Log rank test.

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