Combined cancer testis antigens enhanced prediction accuracy for prognosis of patients with hepatocellular carcinoma

Int J Clin Exp Pathol. 2015 Apr 1;8(4):3513-28. eCollection 2015.

Abstract

Cancer testis antigens (CTAs) are selectively expressed in malignant cells and can serve as ideal targets for immunotherapy. We investigated the expressions of MAGE-A3, MAGE-A4, MAGE-C2 and NY-ESO-1 to determine if combinatorial expressions of CTAs might be as potential prognostic markers for patients with hepatocellular carcinoma (HCC). In tumor tissues of 142 HCC patients, the mRNA expressions of MAGE-A3, MAGE-A4, MAGE-C2 and NY-ESO-1 were 78.9%, 33.8%, 74.6% and 14.1% respectively. Furthermore, the expressions of MAGE-A3, MAGE-A4 and combination of MAGE-A3, MAGE-A4 and NY-ESO-1 (CTAs-A3/A4/NY) showed positive correlations with serum AFP, tumor stages and Ki-67 (P < 0.05). In addition, mRNA expressions of CTAs were significantly consistent with protein expressions of CTAs by immunohistochemistry (P > 0.05). Receiver operating characteristic curves (ROC) analysis showed that CTAs-A3/A4/NY had larger areas under ROC curve (0.768), specificity (99.1%), Youden's index (44.6), positive predictive value (90.9%) and negative predictive value (89.9%) for predicting HCC recurrence than other CTAs. Moreover, the combinatorial expression of CTAs-A3/A4/NY was significantly associated with HCC recurrence by Kaplan-Meier analysis (HR = 69.36, P < 0.01) and multivariate Cox analysis (RR = 17.11, P < 0.01). The combinatorial expression of CTAs-A3/A4/NY mRNA promotes the predictive accuracy of HCC recurrence and itself may be a potential target for immunotherapy of HCC as well.

Keywords: Hepatocellular carcinoma; cancer testis antigen; marker; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • ROC Curve
  • Testicular Neoplasms / immunology*
  • Testis / immunology
  • Testis / metabolism
  • Testis / pathology

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor