B7-H4 is a prognostic biomarker for poor survival in patients with pancreatic cancer

Hum Pathol. 2017 Aug:66:79-85. doi: 10.1016/j.humpath.2017.05.023. Epub 2017 Jun 23.

Abstract

B7-H4 belongs to the immune costimulatory B7 family and is thought to negatively regulate T-cell-mediated immunity, and may contribute an important role in tumor immune evasion. Although the expression of B7-H4 has been observed in human pancreatic cancer, the prognostic significance of this expression is poorly understood. This present study explored the prognostic value of B7-H4 in pancreatic cancer. Patients with pancreatic cancer and healthy controls were recruited at the Second Affiliated Hospital to Zhejiang University from January 2011 to December 2014. Expression of B7-H4 was assessed by immunohistochemistry. Immunohistochemical analysis indicated that B7-H4 was expressed in 100% (188/188) of the pancreatic cancer tumor tissue samples, while only in 68% (17/25) of normal pancreatic tissue samples. Furthermore, the expression levels of B7-H4 in pancreatic cancer patients were significantly higher than in controls (P<.01). A significant difference in B7-H4 expression was observed between patients with late tumor-node-metastasis (TNM) stage (III and IV) and early TNM stage (I and II) (P<.01). The expression of B7-H4 was associated with distant metastasis (P<.01) and differentiation (P<.01). In addition, B7-H4 expression (P<.01), distant metastasis (P<.01), TNM stage (P<.01), differentiation (P<.01) and chemotherapy treatment (P<.05) were indicators of poor overall survival time. Multivariate survival analysis indicated that B7-H4 expression, distant metastasis, and chemotherapy treatment (P<.05) were independent prognostic indicators of poor overall survival. In conclusion, B7-H4 is highly expressed in pancreatic cancer, and is an independent predictor of poor prognosis in patients with pancreatic cancer. B7-H4 may represent an immunotherapeutic target in pancreatic cancer.

Keywords: B7-H4; Biomarker; Immunohistochemistry; Pancreatic cancer; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Pancreatic Ductal / immunology*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / secondary
  • Carcinoma, Pancreatic Ductal / therapy
  • Case-Control Studies
  • China
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Odds Ratio
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy
  • Proportional Hazards Models
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1 / analysis*

Substances

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