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脑胶质瘤组织NPAS2时钟基因启动子区甲基化与预后的关系
杜权, 董晓巧, 俞文华, 朱强, 车志豪, 王昊, 杨定博, 沈永锋, 江力
浙江大学医学院附属杭州市第一人民医院神经外科
摘要:
目的探讨脑胶质瘤组织NPAS2时钟基因启动子区甲基化与预后的关系。方法采用甲基化特异性PCR检测102例脑胶质瘤组织及其癌旁正常组织NPAS2时钟基因启动子区甲基化状态，并分析脑胶质瘤组织NPAS2时钟基因启动子区甲基化状态与患者临床特征、5年总生存期的关系。结果脑胶质瘤组织NPAS2时钟基因启动子区甲基化频率明显高于癌旁正常组织（P＜0.05）。WHO分级Ⅲ~Ⅳ级脑胶质瘤组织NPAS2时钟基因启动子区甲基化频率明显高于Ⅰ~Ⅱ级脑胶质瘤组织（P＜0.05）。肿瘤全切除与否（HR=0.585，95%CI：0.353~0.969，P＜0.05）、肿瘤直径（HR=1.970，95%CI：1.196~3.243，P＜0.05）、WHO分级（HR=1.786，95%CI：1.110~2.874，P＜0.05）、脑胶质瘤组织NPAS2时钟基因启动子区甲基化状态（HR=2.115，95%CI：1.223~3.656，P＜0.05）是影响患者5年总生存期的独立危险因素。结论NPAS2时钟基因启动子区甲基化与脑胶质瘤恶性程度有关，其甲基化修饰是脑胶质瘤患者长期预后不良的独立危险因素。
关键词:  脑胶质瘤 启动子区 甲基化 时钟基因 生存分析
DOI：10.12056/j.issn.1006-2785.2018.40.18.2017-2051
分类号:
基金项目:浙江省医药卫生科技计划项目（2014KYA168）
Relationship between methylation of NPAS2 clock gene promoter region and long-term prognosis in patients with brain glioma
Hangzhou First People's Hospital
Abstract:
Objective To investigate relationship between methylation status of NPAS2 clock gene promoter region and long-term prognosis in patients with brain glioma. Methods Methylation-specific PCR method was used to determine methylation status in NPAS2 clock gene promoter region of 102 glioma tissues and 102 normal brain tissue. Relationship between methylation levels of NPAS2 clock gene and clinicopathological fetures and 5-year overall survival of patients was analyzed. Results Methylation frequency in promoter region of NPAS2 clock gene was significantly higher in glioma tissue than that in normal brain tissue (P＜0.05). The methylation frequency was significantly higher in glioma patients of WHO grade Ⅲ-Ⅳ than that of WHO grade Ⅰ-Ⅱ(P＜0.05). Cox regression model showed that extent of tumor resection (HR=0.585, 95%CI:0.353-0.969, P＜ 0.05), tumor diameter (HR=1.970, 95%CI:1.196-3.243, P＜0.05), WHO grade (HR=1.786, 95%CI:1.110-2.874, P＜0.05) and methylation status in promoter region of NPAS2 clock gene (HR=2.115, 95%CI:1.223-3.656, P＜0.05) were the independent risk factors for 5-year overall survival of patients. Conclusion Methylation status in promoter region of NPAS2 clock gene is closely related to malignant degree of brain glioma and is an independent risk factor for poor prognosis of glioma patients.
Key words:  Glioma Promoter region Methylation Clock gene Survival analysis