Expression and Prognostic Relevance of GAGE1 and XAGE1 Cancer/Testis Antigens in Head and Neck Squamous Cell Carcinoma

Abstract

Background: In the last decades, survival rates in head and neck squamous cell carcinoma (HNSCC) have not changed, with a five-year survival of only 50%. Thus, there is a great need for the identification of new molecular targets and development of novel therapeutic strategies. Cancer-testis antigens (CTAs) are expressed in various types of tumor but rarely in healthy normal tissues. Therefore, they appear as ideal targets for immunotherapy approaches, as well as, unique markers for cancer diagnosis/prognosis.

Objective: This study evaluated the expression pattern of cancer/testis antigens (CTA) in HNSCC samples and correlated the expression data with the clinicopathological prognostic variables.

Methods: An in silico screening was performed using all CTA genes cataloged on the CTDatabase and the expression of the eight CTA genes (ARMC3, DDX53, FTHL17, GAGE1, MAGEA11, SYCE1, TCP11, and XAGE1) was examined in 89 HNSCC and 20 normal mucosa samples using RT-PCR analysis.

Results: GAGE1 (48.3%), XAGE1 (40.4%) and MAGEA11 (19.1%) were frequently and specifically expressed in HNSCC samples and 68.5% of the cases expressed at least one of these antigens. Moreover, GAGE1 and XAGE1 mRNA positivity was significantly associated with the presence of metastasis in the lymph nodes (p=0.038 and p=0.023, respectively) and, by multivariate analysis, male gender (p=0.032), advanced clinical stage (p=0.018) and mRNA positivity for GAGE1 (p=0.010) were independent prognostic factors for overall survival.

Conclusion: These findings suggest GAGE1 and XAGE1 expressions to be useful as prognostic markers for HNSCC.

Keywords: GAGE1; Head and neck squamous cell carcinoma; XAGE1; cancer/testis antigens; mRNA expression; prognostic markers..