A REST derived gene signature stratifies glioblastomas into chemotherapy resistant and responsive disease.
A REST derived gene signature stratifies glioblastomas into chemotherapy resistant and responsive disease.
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DOI：
10.1186/1471-2164-13-686
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发表时间：
2012-12-07
期刊：
影响因子：
4.4
通讯作者：
Roopra A
中科院分区：
文献类型：
--
作者：
Wagoner MP;Roopra A
胶质母细胞瘤是成人最常见的中枢神经系统肿瘤，在美国每年有9000例。多形性胶质母细胞瘤是最具侵袭性的胶质瘤亚型，一年生存率为18%，两年生存率为3%。最近的工作强调了转录因子RE1沉默转录因子在胶质母细胞瘤中的作用，但REST功能如何与疾病预后相关尚未被描述。使用生物信息学方法和对公开可用的微阵列数据集的挖掘，我们描述了一种侵袭性的胶质瘤亚型，该亚型由来自REST的基因签名定义。利用这个REST基因信号，我们预测晚期胶质母细胞瘤的REST功能增强。我们比较了基于休息状态和治疗方案的肿瘤之间的疾病结果，并描述了休息的下游靶点，这可能有助于在REM肿瘤中观察到高剂量化疗所观察到的益处减少。我们提供的人类数据显示，与非REM胶质瘤相比，REM肿瘤患者的无病生存期更短。重要的是，REM肿瘤对多轮化疗无效，患者对这一治疗路线没有反应。这份报告首次描述了REST基因标记，它预测了对多轮化疗的反应，多轮化疗是这种疾病的主流治疗方法。其余基因特征对胶质母细胞瘤的治疗可能具有重要的临床意义。
Glioblastomas are the most common central nervous system neoplasia in adults, with 9,000 cases in the US annually. Glioblastoma multiformae, the most aggressive glioma subtype, has an 18% one-year survival rate, and 3% two year survival rate. Recent work has highlighted the role of the transcription factor RE1 Silencing Transcription Factor, REST in glioblastoma but how REST function correlates with disease outcome has not been described. Using a bioinformatic approach and mining of publicly available microarray datasets, we describe an aggressive subtype of gliomas defined by a gene signature derived from REST. Using this REST gene signature we predict that REST function is enhanced in advanced glioblastoma. We compare disease outcomes between tumors based on REST status and treatment regimen, and describe downstream targets of REST that may contribute to the decreased benefits observed with high dose chemotherapy in REM tumors. We present human data showing that patients with “REST Enhanced Malignancies” (REM) tumors present with a shorter disease free survival compared to non-REM gliomas. Importantly, REM tumors are refractory to multiple rounds of chemotherapy and patients fail to respond to this line of treatment. This report is the first to describe a REST gene signature that predicts response to multiple rounds of chemotherapy, the mainline therapy for this disease. The REST gene signature may have important clinical implications for the treatment of glioblastoma.
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影响因子：
12.4
作者：
Shapira, S.;Barkan, B.;Stein, R.
通讯作者：
Stein, R.
影响因子：
3.7
作者：
Abrajano JJ;Qureshi IA;Gokhan S;Zheng D;Bergman A;Mehler MF
通讯作者：
Mehler MF
影响因子：
4.7
作者：
Fuse, T;Tanikawa, M;Yamada, K
通讯作者：
Yamada, K
DOI：
10.1073/pnas.0710052104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Beroukhim, Rameen;Getz, Gad;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
64.5
作者：
Ballas, N;Grunseich, C;Mandel, G
通讯作者：
Mandel, G