title: Clinical significance of the B7-H4 coregulatory molecule as a novel prognostic marker in gastric cancer.
abstract: 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.
authors: 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. arigami@m.kufm.kagoshima-u.ac.jp
authors: Takaaki
authors: T
authors: Arigami
authors: Yoshikazu
authors: Y
authors: Uenosono
authors: Sumiya
authors: S
authors: Ishigami
authors: Takahiko
authors: T
authors: Hagihara
authors: Naoto
authors: N
authors: Haraguchi
authors: Shoji
authors: S
authors: Natsugoe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001707:Biopsy, Needle; D045744:Cell Line, Tumor; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005743:Gastrectomy / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision / Q000379:methods; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012313:RNA / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013274:Stomach Neoplasms / Q000097:blood* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human; D012313:RNA