Glioma Malignancy-Dependent NDRG2 Gene Methylation and Downregulation Correlates with Poor Patient Outcome.
Glioma Malignancy-Dependent NDRG2 Gene Methylation and Downregulation Correlates with Poor Patient Outcome.
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DOI：
10.7150/jca.9140
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发表时间：
2014
影响因子：
3.9
通讯作者：
Kazlauskas A
中科院分区：
文献类型：
--
作者：
Skiriutė D;Steponaitis G;Vaitkienė P;Mikučiūnas M;Skauminas K;Tamašauskas A;Kazlauskas A
目的：NDRG2（N-myc下游调节基因2）基因参与重要的生物过程：细胞分化、生长和凋亡。多项分子研究表明 NDRG2 是一种有前途的脑肿瘤病理诊断标记物。该研究的目的是调查表观遗传修饰和 NDRG2 活性的变化如何影响神经胶质瘤恶性肿瘤和患者的预后。方法：以137例不同恶性级别的胶质瘤为研究材料：I级毛细胞星形细胞瘤14例，II级弥漫性星形细胞瘤45例，III级间变性星形细胞瘤29例，IV级星形细胞瘤（胶质母细胞瘤）49例。使用甲基化特异性 PCR 进行启动子甲基化分析，而 RT-PCR 和蛋白质印迹分析用于测量 NDRG2 表达水平。结果：我们证明，与低级别星形细胞瘤相比，胶质母细胞瘤标本中 NDRG2 基因甲基化频率增加，而 mRNA 和蛋白质水平表达均显着降低。 NDRG2 转录物和蛋白质水平与启动子甲基化状态不相关，表明神经胶质瘤中存在可能以组织特异性方式运作的替代调节基因表达机制。 Kaplan-Meier 分析显示，根据 NDRG2 甲基化状态以及 mRNA 和蛋白质表达水平分层的神经胶质瘤的生存时间存在显着差异。结论：我们的研究结果强调了在肿瘤生物标志物研究中将表观遗传学数据与 mRNA 和蛋白质水平的基因表达模式相结合的有用性，并表明 NDRG2 下调可能对神经胶质瘤进展产生影响，同时与较高的恶性程度相关。
Aims: NDRG2 (N-myc downstream regulated gene 2) gene is involved in important biological processes: cell differentiation, growth and apoptosis. Several molecular studies have shown NDRG2 as a promising diagnostic marker involved in brain tumor pathology. The aim of the study was to investigate how changes in epigenetic modification and activity of NDRG2 reflect on glioma malignancy and patient outcome. Methods: 137 different malignancy grade gliomas were used as the study material: 14 pilocytic astrocytomas grade I, 45 diffuse astrocytomas grade II, 29 anaplastic astrocytomas grade III, and 49 grade IV astrocytomas (glioblastomas). Promoter methylation analysis has been carried out by using methylation-specific PCR, whereas RT-PCR and Western-blot analyses were used to measure NDRG2 expression levels. Results: We demonstrated that NDRG2 gene methylation frequency increased whereas expression at both mRNA and protein levels markedly decreased in glioblastoma specimens compared to the lower grade astrocytomas. NDRG2 transcript and protein levels did not correlate with the promoter methylation state, suggesting the presence of alternative regulatory gene expression mechanisms that may operate in a tissue-specific manner in gliomas. Kaplan-Meier analyses revealed significant differences in survival time in gliomas stratified by NDRG2 methylation status and mRNA and protein expression levels. Conclusions: Our findings highlight the usefulness of combining epigenetic data to gene expression patterns at mRNA and protein level in tumor biomarker studies, and suggest that NDRG2 downregulation might bear influence on glioma tumor progression while being associated with higher malignancy grade.
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影响因子：
50.3
作者：
Phillips, HS;Kharbanda, S;Aldape, K
通讯作者：
Aldape, K
影响因子：
2
作者：
Li, Wei;Chu, Dake;Sun, Boqian
通讯作者：
Sun, Boqian
影响因子：
2.7
作者：
Piepoli A;Cotugno R;Merla G;Gentile A;Augello B;Quitadamo M;Merla A;Panza A;Carella M;Maglietta R;D'Addabbo A;Ancona N;Fusilli S;Perri F;Andriulli A
通讯作者：
Andriulli A
局灶性脑缺血再灌注后大鼠脑内NDRG2的时空表达
影响因子：
2.9
作者：
Li, Yan;Shen, Lan;Xiong, Lize
通讯作者：
Xiong, Lize
影响因子：
4.4
作者：
Herskowitz, Jeremy H.;Seyfried, Nicholas T.;Duong, Duc M.;Xia, Qiangwei;Rees, Howard D.;Gearing, Marla;Peng, Junmin;Lah, James J.;Levey, Allan I.
通讯作者：
Levey, Allan I.