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. 2018 Mar;8(3):513-519.
doi: 10.3892/mco.2018.1558. Epub 2018 Jan 19.

MAGE-A9 in head and neck cancer: Prognostic value and preclinical findings in the context of irradiation

Till J Meyer  1 , Stefan Hartmann  1 , Gisela Wohlleben  2 , Muna Brisam  1 , Axel Seher  1 , Alexander C Kübler  1 , Bülent Polat  2 , Urs D A Müller-Richter  1
Affiliations

MAGE-A9 in head and neck cancer: Prognostic value and preclinical findings in the context of irradiation

Till J Meyer et al. Mol Clin Oncol. 2018 Mar.

Abstract

Radiotherapy alone, or as an addition to surgery is important for the treatment of head and neck squamous cell carcinoma (HNSCC). In addition to their expression in germ cells, melanoma associated antigens-A (MAGE-A) are only expressed in malignant tissue. Notably, there is a known correlation between MAGE-A9 expression and poor prognosis in HNSCC patients. However, current knowledge regarding the function of MAGE-A9 expression, particularly in the context of irradiation, is limited. MAGE-A9 expression in 37 oral squamous cell carcinoma patents was immunohistochemically determined and analyzed for overall survival by the Kaplan-Meier log-rank test. Next, the expression of MAGE-A9 was determined by reverse transcription-quantitative polymerase chain reaction in HNSCC cell lines prior to and following irradiation with 2 Gray. The radiosensitivity of each cell line was determined using a clonogenic survival assay. There was a significantly (P=0.0468) longer overall survival in patients with a low level of MAGE-A9 expression. The median overall survival in patients with high MAGE-A9 expression was 47% compared to 73% in the group with low MAGE-A9 expression. The cell lines revealed a distinct expression pattern of MAGE-A9. Following irradiation of the cell lines, a significant enhancement of MAGE-A9 mRNA expression levels was observed. The most prominent alteration in MAGE-A9 expression was observed in the most radioresistant cell line. A high MAGE-A9 expression level correlates significantly with lower overall survival in HNSCC patients. Additionally, irradiation increased the MAGE-A9 mRNA levels in all five HNSCC cell lines, and the most resistant cell line demonstrated the greatest increase in MAGE-A9 expression following irradiation.

Keywords: MAGE-A9; head and neck cancer; head and neck squamous cell carcinoma; irradiation; melanoma-associated antigens-A; radiotherapy.

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Figures

Figure 1.
Figure 1.
Patient data in both groups shows balanced cohorts for MAGE-A9 high and MAGE-A9 low. MAGE, melanoma associated antigens.
Figure 2.
Figure 2.
Overall survival of patients with a low vs. a high level of MAGE-A9-tumour expression. By the immunohistochemical grade of MAGE-A9 expression, the patients were divided to a group of low (n=19) or high (n=18) MAGE-A9 expression. The overall survival is significantly (P=0.0468) lower in the group with a high level of MAGE-A9 expression. The surviving fraction at five years was 73.7% for the MAGE-A9 low group and 47.4% for the MAGE-A9 high group. MAGE, melanoma associated antigens.
Figure 3.
Figure 3.
Fold-change of MAGE-A9 after irradiation. After irradiation of five HNSCC cell lines with a dose of 2 Gy, the MAGE-A9 expression was analysed by RT-PCR. 48 h after irradiation there was a statistically significant increase in the MAGE-A9 mRNA level in relation to β-actin. HNSCC, head and neck squamous cell carcinoma; MAGE, melanoma associated antigens.
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