Overexpression of MAGE-D4 in colorectal cancer is a potentially prognostic biomarker and immunotherapy target

Int J Clin Exp Pathol. 2014 Jun 15;7(7):3918-27. eCollection 2014.

Abstract

Melanoma-associated antigen D4 (MAGE-D4) is a novel member of MAGE family. This study aimed to examine the expression and immunogenicity of MAGE-D4 in colorectal cancer (CRC) to determine its potential as a prognosis and immunotherapeutic target. The expression of MAGE-D4 mRNA and protein was determined by RT-PCR and immunohistochemistry (IHC) in CRCs with paired adjacent non-tumor tissues, colorectal adenomas and normal colorectal tissues, respectively. Sera from 64 CRC patients were tested for MAGE-D4 antibody by ELISA. MAGE-D4 mRNA was more frequently expressed in CRCs (76.7%, 46/60) than in adjacent non-tumor tissues (15.0%, 9/60). MAGE-D4 protein was detected in all the CRC tissues tested, 70.0% of which showed high expression. There was no MAGE-D4 protein detected in any paired adjacent non-tumor tissue. No MAGE-D4 expression was found in colorectal adenomas and normal colorectal tissues by either RT-PCR or immunohistochemistry. Patients with high MAGE-D4 protein expression had significantly shorter overall survival than those with low MAGE-D4 protein expression (median, 68.6 vs 122.2 months; P=0.030). Furthermore, multivariate analysis exhibited high MAGE-D4 protein expression had a trend toward an independent prognostic factor (hazard ratio: 6.124; P=0.050). Humoral immunity to MAGE-D4 was detected in 12 of 64 (18.8%) CRC patients' sera but not in 77 healthy donors. There was no correlation between MAGE-D4 expression, serum antibody and clinicopathological parameters. These findings suggest MAGE-D4 may serve as a potentially prognostic biomarker and an attractive target of immunotherapy in CRC.

Keywords: MAGE-D4; Melanoma-associated antigen; colorectal cancer; serum immunoreactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / analysis*
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunohistochemistry
  • Immunotherapy / methods
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Proteins / immunology*
  • Neoplasm Proteins / metabolism*
  • Prognosis
  • Proportional Hazards Models
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • MAGED1 protein, human
  • Neoplasm Proteins