An expression based REST signature predicts patient survival and therapeutic response for glioblastoma multiforme.
An expression based REST signature predicts patient survival and therapeutic response for glioblastoma multiforme.
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基于表达的 REST 特征可预测多形性胶质母细胞瘤的患者生存率和治疗反应
DOI：
10.1038/srep34556
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发表时间：
2016-10-04
影响因子：
4.6
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Liang J;Meng Q;Zhao W;Tong P;Li P;Zhao Y;Zhao X;Li H
神经元基因表达的适当调节对于中枢神经系统的发育和分化至关重要。转录抑制因子REST（repressor element-1 silencing transcription factor）是多能干细胞向神经元祖细胞和成熟神经元分化的关键调节因子。REST活性失调与多种疾病有关，其中最致命的是多形性胶质母细胞瘤（GBM）。在这里，我们开发了一种基于表达的REST签名（EXPREST），这是一种定量测量GBM肿瘤REST活性的设备。EXPREST使用基因表达谱在没有REST的临床病理学评估的情况下稳健地定量REST活性（REST评分）。REST活性的分子表征确定了DNA、RNA、蛋白质和microRNA水平的整体改变，表明REST在GBM肿瘤发生中的广泛作用。虽然最初的目的是捕捉REST活动，REST评分被发现是一个预后因素的总生存。此外，发现具有增强的REST活性的细胞系对IGF 1 R、VEGFR和ABL抑制剂更敏感。相反，具有低REST评分的细胞系对包括丝裂霉素、喜树碱和顺铂在内的细胞毒性药物更敏感。总之，我们的工作表明，REST的治疗靶向为GBM治疗提供了一个有希望的机会。
Proper regulation of neuronal gene expression is crucial for the development and differentiation of the central nervous system. The transcriptional repressor REST (repressor element-1 silencing transcription factor) is a key regulator in differentiation of pluripotent stem cells to neuronal progenitors and mature neurons. Dysregulated REST activity has been implicated in various diseases, among which the most deadly is glioblastoma multiforme (GBM). Here we have developed anexpression-basedRESTsignature (EXPREST), a device providing quantitative measurements of REST activity for GBM tumors. EXPREST robustly quantifies REST activity (REST score) using gene expression profiles in absence of clinic-pathologic assessments of REST. Molecular characterization of REST activity identified global alterations at the DNA, RNA, protein and microRNA levels, suggesting a widespread role of REST in GBM tumorigenesis. Although originally aimed to capture REST activity, REST score was found to be a prognostic factor for overall survival. Further, cell lines with enhanced REST activity was found to be more sensitive to IGF1R, VEGFR and ABL inhibitors. In contrast, cell lines with low REST score were more sensitive to cytotoxic drugs including Mitomycin, Camptothecin and Cisplatin. Together, our work suggests that therapeutic targeting of REST provides a promising opportunity for GBM treatment.
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REST 基因特征可预测神经母细胞瘤细胞系的药物敏感性，并与神经母细胞瘤肿瘤阶段显着相关
影响因子：
5.6
作者：
Liang J;Tong P;Zhao W;Li Y;Zhang L;Xia Y;Yu Y
通讯作者：
Yu Y
影响因子：
1.3
作者：
Gopalakrishnan V
通讯作者：
Gopalakrishnan V
影响因子：
64.5
作者：
Ballas, N;Grunseich, C;Mandel, G
通讯作者：
Mandel, G
影响因子：
5.8
作者：
Hubbell, E;Liu, WM;Mei, R
通讯作者：
Mei, R
影响因子：
8
作者：
Gurrola-Diaz, C;Lacroix, J;Doeberitz, MV
通讯作者：
Doeberitz, MV