High expression and frequently humoral immune response of melanoma-associated antigen D4 in glioma

Int J Clin Exp Pathol. 2014 Apr 15;7(5):2350-60. eCollection 2014.

Abstract

MAGE-D4 is a novel member of MAGE super-family. It has preliminarily been demonstrated that MAGE-D4 mRNA is not expressed in majority of normal tissues except for brain and ovary in which only trace amount of MAGE-D4 mRNA can be detected, but predominantly expressed in glioma. MAGE-D4 protein expression and its immunogenicity in glioma have not been elucidated well. This study was designed to analyze MAGE-D4 expression both at mRNA and protein level, characteristic of humoral immune response, and their relationships with glioma patients' clinicopathological parameters. Recombinant MAGE-D4 protein and antiserum were generated. Quantitative RT-PCR analysis revealed that MAGE-D4 mRNA expression was overall up-regulated in 41 glioma specimens compared with that in 14 normal brain tissues. Immunohistochemistry analysis showed that 78% (21/27) glioma tissues expressed MAGE-D4 protein, which was predominantly located in the cytoplasm of tumor cells, but absent in any neuroglia cell of normal brain tissues. ELISA analysis demonstrated that humoral response against MAGE-D4 was detected in 17% (7/41) of glioma patients' sera but not in 77 healthy donors. No apparent correlation was observed between the expression and immunogenicity of MAGE-D4 with clinicopathological parameters of glioma. In summary, these results indicate that MAGE-D4 is highly expressed in glioma and can develop specifically humoral response in glioma patients, which supports that it may be a promising biomarker for glioma diagnosis and immunotherapy.

Keywords: Glioma; gene expression; immunogenicity; melanoma-associated antigen D4; tumor antigen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, Neoplasm / analysis
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology*
  • Biopsy
  • Brain Neoplasms / blood
  • Brain Neoplasms / genetics
  • Brain Neoplasms / immunology*
  • Brain Neoplasms / pathology
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / blood
  • Glioma / genetics
  • Glioma / immunology*
  • Glioma / pathology
  • Humans
  • Immunity, Humoral*
  • Immunoglobulin G / blood
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology*
  • RNA, Messenger / analysis
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation
  • Young Adult

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Immunoglobulin G
  • MAGED1 protein, human
  • Neoplasm Proteins
  • RNA, Messenger