Hypermethylation of testis derived transcript gene promoter significantly correlates with worse outcomes in glioblastoma patients
Hypermethylation of testis derived transcript gene promoter significantly correlates with worse outcomes in glioblastoma patients
复制标题
睾丸来源的转录基因启动子的高甲基化与胶质母细胞瘤患者的较差预后显着相关
DOI：
10.3760/cma.j.issn.0366-6999.20123570
复制
发表时间：
2013-06-05
影响因子：
6.1
通讯作者：
Zhang Quan-geng
中科院分区：
文献类型：
--
作者：
Wang Li-jia;Bai Yu;Zhang Quan-geng
背景胶质母细胞瘤是最常见、最致命的中枢神经系统肿瘤。全基因组低甲基化和部分CpG岛高甲基化是这些恶性肿瘤的共同特征，但这些甲基化异常对胶质母细胞瘤的影响仍很不清楚。06-甲基鸟嘌呤-DNA甲基转移酶启动子的甲基化是目前唯一被证实的替莫唑胺治疗效果更好的分子预测因子。为了更好地了解CpG岛甲基化状态与患者预后的关系，本研究启动了33例原发胶质母细胞瘤(PGBM)和9例继发性胶质母细胞瘤(SGBM)的DNA甲基化图谱，以期寻找有价值的预后和治疗靶点。方法通过对胶质母细胞瘤进行基因芯片分析，评估睾丸衍生转录(TES)基因启动子的甲基化状态以及TES甲基化对pGBM患者临床预后的预测价值。对33个pGBM和9个SGBM之间甲基化差异显著的基因进行微阵列显着性分析。生存曲线按Kaplan-Meier法计算，曲线间差异采用对数等级检验。用5-氮杂-2-脱氧胞苷(5-aza-2-deoxcytidine，5-aza-DC)处理胶质母细胞瘤细胞系U87和U251，检测细胞生物学行为。
Background Glioblastoma is the most common and lethal cancer of the central nervous system. Global genomic hypomethylation and some CpG island hypernnethylation are common hallmarks of these malignancies, but the effects of these methylation abnormalities on glioblastomas are still largely unclear. Methylation of the 06-methylguanine-DNA methyltransferase promoter is currently an only confirmed molecular predictor of better outcome in temozolomide treatment. To better understand the relationship between CpG island methylation status and patient outcome, this study launched DNA methylation profiles for thirty-three primary glioblastomas (pGBMs) and nine secondary glioblastonnas (sGBMs) with the expectation to identify valuable prognostic and therapeutic targets.Methods We evaluated the nnethylation status of testis derived transcript (TES) gene promoter by microarray analysis of glioblastomas and the prognostic value for TES methylation in the clinical outcome of pGBM patients. Significance analysis of microarrays was used for genes significantly differently methylated between 33 pGBM and nine sGBM. Survival curves were calculated according to the Kaplan-Meier method, and differences between curves were assessed using the log-rank test. Then, we treated glioblastoma cell lines (U87 and U251) with 5-aza-2-deoxycytidines (5-aza-dC) and detected cell biological behaviors.Results Microarray data analysis identified TES promoter was hypermethylated in pGBMs compared with sGBMs (P