Zhai Xiaolu, Xu Liqin, Zhang Siya, Zhu Huijun, Mao Guoxin, Huang Jianfei
Department of Chemotherapy, Nantong University Affiliated Hospital, Nantong 226001, Jiangsu, China.
Department of Respiratory, Nantong University Affiliated Hospital, Nantong 226001, Jiangsu, China.
Oncotarget. 2016 Jan 26;7(4):4871-81. doi: 10.18632/oncotarget.6741.
A variety of melanoma-associated antigen-A (MAGE-A) protein are commonly detected in lung cancers. Their biological function is not well characterized but may involve cell cycle progression and the regulation of apoptosis. We hypothesized that MAGE-A9 is involved in the regulation of apoptosis. To test this hypothesis, we evaluated MAGE-A9 protein expression by immunohistochemical staining and we assessed the relationship between the expression of MAGE-A9 and clinical pathological parameters. In addition, we investigated the effect of MAGE-A9 down-regulation in lung adenocarcinoma. The results showed that a high expression level of MAGE-A9 protein in lung adenocarcinoma tumor cells was related to larger tumor diameter (P = 0.013) and poor differentiation (P = 0.029). Cox regression analysis revealed that the expression of MAGE-A9 in lung adenocarcinoma tumor cells (P < 0.001) is an independent prognostic factor in five-year survival rates. NSCLC cells with silenced MAGE-A9 had decreased cell proliferation, migration and invasion in cell culture compared to corresponding control cells. The NSCLC cells showing down-regulated MAGE-A9 induced the expression of apoptosis-associated proteins. In addition, MAGE-A9 was associated with resistance to conventional chemotherapeutic agents. Our findings provide evidence that MAGE-A9 could be a potential therapeutic target in NSCLC.
多种黑色素瘤相关抗原A（MAGE-A）蛋白在肺癌中普遍被检测到。它们的生物学功能尚未得到充分表征，但可能涉及细胞周期进程和细胞凋亡的调控。我们推测MAGE-A9参与细胞凋亡的调控。为验证这一假设，我们通过免疫组织化学染色评估MAGE-A9蛋白表达，并评估MAGE-A9表达与临床病理参数之间的关系。此外，我们研究了MAGE-A9下调对肺腺癌的影响。结果显示，肺腺癌肿瘤细胞中MAGE-A9蛋白的高表达水平与更大的肿瘤直径（P = 0.013）和低分化（P = 0.029）相关。Cox回归分析显示，肺腺癌肿瘤细胞中MAGE-A9的表达（P < 0.001）是五年生存率的独立预后因素。与相应对照细胞相比，MAGE-A9沉默的非小细胞肺癌（NSCLC）细胞在细胞培养中的细胞增殖、迁移和侵袭能力降低。MAGE-A9表达下调的NSCLC细胞诱导凋亡相关蛋白的表达。此外，MAGE-A9与对传统化疗药物的耐药性有关。我们的研究结果提供了证据，表明MAGE-A9可能是NSCLC的一个潜在治疗靶点。
