Expression and clinical significance of cancer-testis genes in clear cell renal cell carcinoma

Int J Clin Exp Pathol. 2014 Jun 15;7(7):4112-9. eCollection 2014.

Abstract

Cancer-testis (CT) antigens, which are encoded by CT genes, have been recognized as a group of highly attractive targets for cancer immunotherapy. However, the expression and clinical relevance of CT genes in clear cell renal cell carcinoma (ccRCC) remains largely unknown. The present study aims to analyze the expression profile of 6 individual CT genes including MAGE-A1, MAGE-A3, MAGE-A12, cTAGE-1, cTAGE-2, and NY-ESO-1 in ccRCC and further investigate their possible correlations with clinicopathologic characteristics. The mRNA expressions of these CT genes were detected using reverse transcriptase-polymerase chain reaction (RT-PCR) in 105 ccRCC tissue samples (T1-2 in 70 samples, T3-4 in 35 samples; G1-2 in 65 samples, G3-4 in 40 samples) as well as the paired adjacent normal tissues. The most frequently expressed CT gene was MAGE-A3 (27.6%), followed by MAGE-A12 (23.8%), NY-ESO-1 (21%), MAGE-A1 (20%), cTAGE-1 (17.1%), and cTAGE-2 (14.3%). In contrast, no expression of CT genes was detected in the paired adjacent normal tissues. Furthermore, the MAGE-A3 protein expression was determined by Western blot and immunohistochemistry. MAGE-A3 protein was expressed in 21.9% ccRCC samples with a cytoplasmic staining pattern. No MAGE-A3 protein expression was found in the paired adjacent normal tissues. There was a significant correlation between MAGE-A3 expression at both mRNA (P =0.045) and protein (P = 0.03) levels with advanced stages of the disease. Taken together, CT genes may serve as promising targets of specific immunotherapy for ccRCC and particularly, MAGE-A3 may serve as a potential prognostic marker for ccRCC patients.

Keywords: Cancer-testis (CT) gene; clear cell renal cell carcinoma; immunotherapy; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / analysis*
  • Antigens, Neoplasm / biosynthesis
  • Biomarkers, Tumor / analysis
  • Blotting, Western
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptome

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • MAGEA3 protein, human
  • Neoplasm Proteins
  • RNA, Messenger