A Comprehensive Expression Analysis of Cancer Testis Antigens in Head and Neck Squamous Cell Carcinoma Revels MAGEA3/6 as a Marker for Recurrence

Abstract

Despite significant advances in the treatment of head and neck squamous cell carcinoma (HNSCC), the survival rate has not changed in the last decades. Therefore, the development of novel therapeutic strategies is pursued. Cancer-testis antigens (CTA) are strong immunogenic proteins with a tumor-restricted expression pattern, and are considered ideal targets for tumorspecific immunotherapeutic approaches. In this study, using an in silico approach, we selected, among 139 previously described CTA, candidates to be evaluated in 89 HNSCC and 20 normal mucosa samples. SPANX-CD (71.9%), MAGEB2 (44.9%), MAGEA1 (44.9%), MAGEB6 (32.6%), and CXORF48 (27.0%) were found frequently expressed in HNSCC, and over 85% of the tumors expressed at least one of these five CTAs. The mRNA positivity of CXORF48, MAGEB6, and CRISP2 presented significant associations with recognized clinical features for poor outcome. Furthermore, MAGEA3/6 positivity was associated with significantly better disease-free survival (DFS, P ¼ 0.014), and the expression of this antigen was shown to be an independent prognostic factor for tumor recurrence. In conclusion, one of five selected CTAs is expressed in at least 85% of the HNSCCs, suggesting a possible usage as target for immunotherapeutic approaches, and the mRNA-positivity for MAGEA3/ 6 is shown to be an independent marker for DFS. Mol Cancer Ther; 14(3); 828-34. Ó2015 AACR.

A four‐gene‐based prognostic model predicts overall survival in patients with hepatocellular carcinoma

“…In this study, we show for the first time that MAGEB6 is highly expressed in HCC based on RNA‐seq data in the TCGA database, and its use in the prognostic model was found to independently predict the prognosis of patients with HCC, similar to its predictive utility in head and neck squamous cell carcinoma (HNSCC). MAGEB6 was found to be frequently expressed in HNSCC, and there is a clear association between MAGE6B mRNA positivity and recognized clinical characteristics of unfavourable prognosis, which suggests that MAGE6B may be an interesting target for HNSCC immunotherapy treatment . Therefore, because CTAs are capable of eliciting spontaneous antitumour immune responses, the CTA member MAGEB6 is a promising candidate biomarker for future HCC immunotherapy and is of great importance in the development of cancer vaccines for clinical trials.…”

The expression of the cancer testis antigen MAGE A4: A favorable prognostic biomarker in salivary gland carcinomas related to low tumor grading

“…The relevance of CTAs as prognostic biomarkers has been demonstrated in many malignant tumors such as breast, lung, thyroid, and head and neck squamous cell carcinoma . In contrast, there are only few studies investigating the role of CTAs in salivary gland carcinomas .…”

MAGE expression in head and neck squamous cell carcinoma primary tumors, lymph node metastases and respective recurrences-implications for immunotherapy

“…Another group reported better DFS for MAGE-A3/A6 positive compared to negative patients based on polymerase chain reaction data for MAGE-A3/A6 RNA [20]. MAGE-A6 is a homologue protein to MAGE-A3 and the 57B antibody binds to MAGE-A6 as well, as we have previously shown by ELISA [10].…”

“…Another group showed increased MAGE-A3 RNA expression in a cancer-stem cell population in bladder cancer [15]. Zamuner et al reported reduced incidence of recurrence in MAGE-A3/A6 positive tumors [20]. However, Zamuner et al did not assess MAGE expression in samples of recurrent tumors.…”