Clinical Significance of the B7-H4 Coregulatory Molecule as a Novel Prognostic Marker in Gastric Cancer
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The B7-H4 coregulatory molecule is a member of the B7 family of molecules, which regulate the T-cell-mediated immune response through CD28 receptors. Recently, B7-H4 has been reported to be a negative regulator of the immune response in patients with several malignant diseases. However, few reports have investigated the clinical significance of B7-H4 expression in patients with gastric cancer. In the present study, we analyzed B7-H4 expression and the relationship between its expression and clinicopathological factors including prognosis in gastric cancer.
B7-H4 expression in gastric cancer cell lines and clinical gastric cancer specimens was initially assessed with the reverse transcription-polymerase chain reaction (RT-PCR). Moreover, B7-H4 and CD3 expression in 120 resected specimens from gastric cancer patients were evaluated by immunohistochemistry (IHC).
B7-H4 expression was identified in the gastric cancer cell lines and clinical tumor tissues by RT-PCR. B7-H4 expression was high in 25.8% (31/120) of resected tumor specimens. B7-H4 expression significantly correlated with tumor stage (P = 0.04). The 5-year survival rate was significantly lower in patients with high B7-H4 expression than in those with low B7-H4 expression (P = 0.001). Multivariate analysis demonstrated that B7-H4 expression was an independent prognostic factor (P = 0.035). Immunohistochemical analysis of CD3 expression showed that B7-H4 expression was inversely correlated with the number of tumor infiltrating T lymphocytes (P < 0.001).
The B7-H4 coregulatory molecule is a novel prognostic marker related to the T-cell-mediated immune response, and its pathway may be a molecular target for controlling tumor progression in patients with gastric cancer.
KeywordsGastric Cancer Gastric Cancer Patient Gastric Cancer Cell Line Resected Primary Tumor Primary Tumor Cell
This work was supported in part by a grant-in-aid (no. 22791256) for scientific research from the Ministry of Education, Science, Sports, and Culture, Japan. The authors are grateful to Y. Nishizono and A. Harada for technical assistance.
Conflict of interest
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