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黑色素瘤相关抗原 A2 在神经胶质瘤中过表达,并与神经胶质瘤患者的预后不良相关。

Melanoma-associated antigen A2 is overexpressed in glioma and associated with poor prognosis in glioma patients.

机构信息

Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China

出版信息

Neoplasma. 2018;65(4):604-609. doi: 10.4149/neo_2018_170625N440.

Abstract

Malignant glioma is the most common and aggressive primary brain tumor and the overall prognosis for glioma patients remains poor. Clarification of the molecular mechanism responsible for glioma progression is critical for the effective treatment of glioma. Melanoma antigen gene (MAGE)-A2 (MAGEA2) is a member of the MAGE-A family proteins widely studied for cancer vaccine development and identification of tumor markers. However, MAGEA2 clinical significance  and biological function in glioma remain unclear, especially for the prognosis of glioma patients. This study investigates MAGEA2 expression in glioma tissue samples and its significance in predicting glioma patient prognosis. MAGEA2 protein expression in tissue samples was measured by immunohistochemistry and western blotting, and MAGEA2 mRNA expression was determined by real-time polymerase chain reaction. Our results confirmed that MAGEA2 mRNA and protein expression levels were upregulated in glioma tissues, compared with normal brain tissue. The high expression of MAGEA2 in glioma tissues significantly correlated with World Health Organization advanced grade. Univariate and multivariate analyses revealed that high MAGEA2 expression is an independent prognostic factor for glioma patient poor overall survival. The P53 mRNA expression levels were downregulated in glioma tissues compared to noncancerous brain tissue and MAGEA2 expression negatively correlated with P53 expression. Taken together, our results suggest that MAGEA2 plays an oncogenic role in glioma progression, and they provide insight into MAGEA2 application as a novel predictor of clinical outcomes and a potential glioma biomarker.

摘要

恶性脑胶质瘤是最常见和侵袭性最强的原发性脑肿瘤,脑胶质瘤患者的总体预后仍然较差。阐明导致脑胶质瘤进展的分子机制对于脑胶质瘤的有效治疗至关重要。黑色素瘤抗原基因(MAGE)-A2(MAGEA2)是 MAGE-A 家族蛋白的成员,广泛用于癌症疫苗的开发和肿瘤标志物的鉴定。然而,MAGEA2 在脑胶质瘤中的临床意义和生物学功能仍不清楚,特别是对脑胶质瘤患者的预后。本研究调查了 MAGEA2 在脑胶质瘤组织样本中的表达及其对预测脑胶质瘤患者预后的意义。通过免疫组织化学和 Western blot 检测组织样本中 MAGEA2 蛋白的表达,通过实时聚合酶链反应检测 MAGEA2 mRNA 的表达。我们的结果证实,与正常脑组织相比,MAGEA2 mRNA 和蛋白在脑胶质瘤组织中表达上调。MAGEA2 在脑胶质瘤组织中的高表达与世界卫生组织(WHO)高级别显著相关。单因素和多因素分析表明,MAGEA2 高表达是脑胶质瘤患者总生存不良的独立预后因素。与非癌性脑组织相比,P53 mRNA 在脑胶质瘤组织中表达下调,MAGEA2 表达与 P53 表达呈负相关。总之,我们的研究结果表明,MAGEA2 在脑胶质瘤的进展中发挥致癌作用,并为 MAGEA2 作为临床结局的新型预测因子和潜在的脑胶质瘤生物标志物的应用提供了新的见解。

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