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

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


Background: 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.

Methods: 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).

Results: 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).

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Biopsy, Needle
  • Cell Line, Tumor
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Gastrectomy / methods
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymph Node Excision / methods
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • RNA / analysis
  • Real-Time Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Stomach Neoplasms / blood*
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • Survival Analysis
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1 / genetics
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1 / metabolism*


  • Biomarkers, Tumor
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1
  • VTCN1 protein, human
  • RNA