Department of Oral and Maxillofacial Plastic Surgery, Head: Alexander C. Kübler, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany; Interdisciplinary Center for Clinical Research, Head: Matthias Goebeler, University Hospital Würzburg, Josef-Schneider-Straße 2, 97070, Würzburg, Germany.
Department of Oral and Maxillofacial Plastic Surgery, Head: Alexander C. Kübler, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
J Craniomaxillofac Surg. 2018 Mar;46(3):492-497. doi: 10.1016/j.jcms.2017.12.014. Epub 2017 Dec 24.
Melanoma-associated antigen A (MAGE-A) proteins are members of the cancer/testis antigens (CTA), and the expression of these proteins is almost exclusively limited to malignant cells, making them an attractive treatment target. MAGE-A expression is correlated with poor overall survival in several cancers, including head and neck squamous cell carcinoma (HNSCC). Among others, MAGE-A11 was found to be associated with resistance to different antineoplastic and targeted compounds, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We searched The Cancer Genome Atlas (TCGA) database with a focus on MAGE-A and found that MAGE-A overexpression is a common event in HNSCC (27.5%). Furthermore, MAGE-A overexpression was correlated with significantly reduced overall survival (35.45 months vs. 64.78 months, P = 0.0173). In particular, MAGE-A11 overexpression was found in 9% of specimens. We then examined MAGE-A11 expression, the efficacy of EGFR and the EGFR mutational status and the effects of the pan-HER (human EGFR) TKIs erlotinib and afatinib in HNSCC cell lines. Next, we used a model of stable MAGE-A11 overexpression to demonstrate that MAGE-A11 impaired the efficacy of erlotinib and afatinib. In summary, our study provides evidence that MAGE-A11 contributes to erlotinib and afatinib resistance in head and neck cancer cell lines.
黑色素瘤相关抗原 A（MAGE-A）蛋白是癌症/睾丸抗原（CTA）的成员，这些蛋白的表达几乎仅限于恶性细胞，使其成为有吸引力的治疗靶点。MAGE-A 的表达与包括头颈部鳞状细胞癌（HNSCC）在内的几种癌症的总体生存率差相关。在其他蛋白中，MAGE-A11 与对不同抗肿瘤和靶向化合物的耐药性有关，如表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）。我们在癌症基因组图谱（TCGA）数据库中搜索了 MAGE-A，并发现 MAGE-A 的过表达是 HNSCC 的常见事件（27.5%）。此外，MAGE-A 的过表达与总生存率显著降低相关（35.45 个月比 64.78 个月，P = 0.0173）。特别是，9%的标本中发现了 MAGE-A11 的过表达。然后，我们检查了 MAGE-A11 的表达、EGFR 的疗效以及 EGFR 突变状态和泛 HER（人表皮生长因子受体）TKI 厄洛替尼和阿法替尼在 HNSCC 细胞系中的作用。接下来，我们使用稳定过表达 MAGE-A11 的模型证明，MAGE-A11 降低了厄洛替尼和阿法替尼的疗效。总之，我们的研究提供了证据表明，MAGE-A11 有助于头颈部癌细胞系对厄洛替尼和阿法替尼的耐药性。
