脑胶质瘤患者血清黑色素瘤相关抗原-A3特异性细胞毒性T淋巴细胞免疫反应水平及临床意义  

Specific cytotoxic T lymphocyte immune response levels of melanoma-associated antigen-A3 in patients with glioma and its clinical significance

作　　者：李俊 孙继程 杜国新 LI Jun;SUN Jicheng;DU Guoxin(Department of Neurology,Tiemei General Hospital of Liaojian Group,Tieling 112700,Liaoning,China)

机构地区：[1]辽宁省健康产业集团铁煤总医院神经外一科,辽宁铁岭112700

出　　处：《癌症进展》2020年第22期2295-2299,共5页Oncology Progress

摘　　要：目的探讨脑胶质瘤组织中黑色素瘤相关抗原-A3(MAGE-A3)蛋白表达和甲基化状态,血清中特异性细胞毒性T淋巴细胞(CTL)免疫应答及临床意义。方法采用蛋白质印迹(Western blot)法和甲基化特异性聚合酶链反应(MSP-PCR)技术检测56例脑胶质瘤组织和15例正常脑组织中MAGE-A3蛋白表达和基因甲基化状态,采用Gultured酶联免疫斑点法(ELISPOT)检测患者外周血单个核细胞(PBMC)中MAGE-A3特异性CTL免疫反应,并明确二者之间的关系,以及与患者临床特征的关系。结果56例脑胶质瘤组织中MAGE-A3蛋白的表达量为(2.26±1.09),明显高于15例正常脑组织中的(0.44±0.18)(P﹤0.01)。脑胶质瘤组织中MAGE-A3基因启动子甲基化率为55.36%(31/56),明显低于正常脑组织的100%(15/15)(P﹤0.01)。脑胶质瘤患者血清MAGE-A3特异性CTL免疫应答阳性率为33.93%(19/56),平均反应强度为(2301.70±560.33)SFC/106 PBMC。同一患者脑胶质瘤组织中MAGE-A3基因启动子甲基化状态与MAGE-A3蛋白高表达结果一致性一般(Kappa=0.679,P﹤0.01)。同一患者血清MAGE-A3特异性CTL免疫应答阳性与组织中MAGE-A3蛋白高表达结果一致性一般(Kappa=0.464,P﹤0.01)。脑胶质瘤患者血清中MAGE-A3特异性CTL免疫反应强度与组织中MAGE-A3蛋白表达量呈正相关(r=0.788,P﹤0.01)。不同肿瘤大小及临床分期的脑胶质瘤患者血清MAGE-A3特异性CTL免疫反应频率比较,差异均有统计学意义(P﹤0.01)。结论脑胶质瘤组织中MAGE-A3基因启动子区DNA去甲基化导致MAGE-A3蛋白表达量升高,进而刺激机体产生MAGE-A3特异性CTL免疫应答反应,参与肿瘤生长和恶性进展。Objective To investigate the expression of melanoma-associated antigen-A3(MAGE-A3)protein and methylation in glioma tissues and specific cytotoxic T lymphocyte(CTL)immune response in plasma,and its clinical significance.Method Western blot and methylation specific polymerase chain reaction(MSP-PCR)methods were used to detect MAGE-A3 protein and methylation status in 56 glioma tissues and 15 normal brain tissues.Gultured enzymelinked immunosorbent spot assay(ELISPOT)was used to detect the serum specific CTL immune response in glioma patients.The relationship between MAGE-A3 specific CTL immune response and MAGE-A3 protein expressions,their relationship with the clinical features were analyzed.Result Compared with normal brain tissue,MAGE-A3 protein levels in glioma tissues were higher[(2.26±1.09)vs(0.44±0.18),P<0.01],while MAGE-A3 gene promoter methylation rate was lower[55.36%(31/56)vs 100%(15/15),P<0.01].The positive rate of MAGE-A3 specific CTL immune response was 33.93%(19/56),and the average response intensity was(2301.70±560.33)SFC/106 PBMC.The methylation status of MAGE-A3 gene promoter was consistent with the high expression of MAGE-A3 protein(Kappa=0.679,P<0.01).The results of positive serum MAGE-A3 specific CTL immune response and high expression of MAGE-A3 protein in the same patient were generally consistent(Kappa=0.464,P<0.01).There was a positive correlation between MAGE-A3 specific CTL immunoreactivity in serum and MAGE-A3 protein expression in tissues(r=0.788,P<0.01).The frequency of MAGE-A3 specific CTL immune response in patients with different tumor sizes and TNM stages were significantly different(P<0.01).Conclusion DNA demethylation in the promoter region of MAGE-A3 gene in glioma tissue leads to the increase of MAGE-A3 protein expression,which stimulates the body to produce MAGE-A3 specific CTL immune response,and participates in glioma growth and malignant progression.

关 键 词：黑色素瘤相关抗原-A3 脑胶质瘤 基因甲基化 特异性细胞毒性T淋巴细胞免疫应答 临床特征 

分 类 号：R739.41[医药卫生—肿瘤]