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World J Surg. 2011 Sep;35(9):2051-7. doi: 10.1007/s00268-011-1186-4.

Clinical significance of the B7-H4 coregulatory molecule as a novel prognostic marker in gastric cancer.

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Department of Surgical Oncology and Digestive Surgery, Field of Oncology, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.



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.

[Indexed for MEDLINE]

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