Cancer-testis antigen BORIS is a novel prognostic marker for patients with esophageal cancer

Cancer Sci. 2012 Sep;103(9):1617-24. doi: 10.1111/j.1349-7006.2012.02355.x. Epub 2012 Jul 16.

Abstract

Esophageal squamous cell cancer (ESCC) is one of the most common lethal tumors in the world, and development of new diagnostic and therapeutic methods is needed. In this study, cancer-testis antigen, BORIS, was isolated by functional cDNA expression cloning using screening technique with serum IgG Abs from ESCC patients. BORIS was previously reported to show cancer-testis antigen like expression, but its immunogenicity has remained unclear in cancer patients. BORIS was considered to be an immunogenic antigen capable of inducing IgG Abs in patients with various cancers, including four of 11 ESCC patients. Immunohistochemical study showed that the BORIS protein was expressed in 28 of 50 (56%) ESCC tissues. The BORIS expression was significantly associated with lymph node metastasis in ESCC patients with pT1 disease (P = 0.036). Furthermore, the patients with BORIS-positive tumors had a poor overall survival (5-year survival rate: BORIS-negative 70.0% vs BORIS-positive 29.9%, log-rank P = 0.028) in Kaplan-Meier survival analysis and log-rank test. Multivariate Cox proportional hazard model demonstrated that BORIS expression was an independent poor prognostic factor (hazard ratio = 4.158 [95% confidence interval 1.494-11.57], P = 0.006). Downregulation of BORIS with specific siRNAs resulted in decreased cell proliferation and invasion ability of ESCC cell lines. BORIS may be a useful biomarker for prognostic diagnosis of ESCC patients and a potential target for treatment including by BORIS-specific immunotherapy and molecular target therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / immunology
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cloning, Molecular
  • DNA, Complementary
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / immunology
  • Esophageal Neoplasms / diagnosis*
  • Esophageal Neoplasms / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Staging
  • Prognosis

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CTCFL protein, human
  • DNA, Complementary
  • DNA-Binding Proteins
  • Immunoglobulin G