Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma

Br J Cancer. 2012 Jun 26;107(1):116-22. doi: 10.1038/bjc.2012.215. Epub 2012 May 17.

Abstract

Background: The potential for cancer-testis (CT) antigens as targets for immunotherapy in cancer patients has been heavily investigated, and currently cancer vaccine trials based on the CT antigens, MAGE-A3 and NY-ESO-1, are being carried out.

Methods: We used specific q-RT-PCR assays to analyse the expression of the CT genes MAGE-A3, NY-ESO-1 (CTAG1B), LAGE-1 (CTAG2) and PRAME in a panel of bladder tumours from 350 patients with long-term follow-up and detailed treatment information.

Results: Overall, 43% of the tumours expressed MAGE-A3, 35% expressed NY-ESO-1, 27% expressed LAGE-1 and 20% expressed PRAME. In all, 56% of the tumours expressed at least one of the CT genes analysed. Univariate Cox regression analysis of CT gene expression in non-muscle-invasive tumours showed that expression of MAGE-A3 (P=0.026), LAGE-1 (P=0.001) and NY-ESO-1 (P=0.040) was significantly associated with a shorter progression-free survival. In addition, we found that patients with tumours expressing PRAME responded poorly to chemotherapy (P=0.02, χ(2)-test).

Conclusion: Cancer-testis genes are frequently expressed in bladder cancer and especially in tumours of high stage and grade. In addition, the CT gene expression may have both prognostic and predictive value. Development of specific immunotherapy against the CT antigens in bladder cancer may ultimately increase patient survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Antigens, Surface / metabolism
  • DNA Methylation
  • Disease-Free Survival
  • Female
  • Gene Expression
  • Humans
  • Male
  • Membrane Proteins / metabolism*
  • Neoplasm Proteins / metabolism*
  • Prognosis
  • Urinary Bladder Neoplasms / metabolism*

Substances

  • Antigens, Neoplasm
  • Antigens, Surface
  • CTAG1B protein, human
  • CTAG2 protein, human
  • MAGEA3 protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • PRAME protein, human