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胶质母细胞瘤的长非编码 RNA 特征可预测生存。

A long non-coding RNA signature in glioblastoma multiforme predicts survival.

机构信息

Department of Surgery, The University of Hong Kong, Hong Kong.

出版信息

Neurobiol Dis. 2013 Oct;58:123-31. doi: 10.1016/j.nbd.2013.05.011. Epub 2013 May 29.

DOI:10.1016/j.nbd.2013.05.011
PMID:23726844
Abstract

Long non-coding RNAs (lncRNAs) represent the leading edge of cancer research, and have been implicated in cancer biogenesis and prognosis. We aimed to identify lncRNA signatures that have prognostic values in glioblastoma multiforme (GBM). Using a lncRNA-mining approach, we performed lncRNA expression profiling in 213 GBM tumors from The Cancer Genome Atlas (TCGA), randomly divided into a training (n=107) and a testing set (n=106). We analyzed the associations between lncRNA signatures and clinical outcome in the training set, and validated the findings in the testing set. We also validated the identified lncRNA signature in another two independent GBM data sets from Gene Expression Omnibus (GEO), which contained specimens from 68 and 101 patients, respectively. We identified a set of six lncRNAs that were significantly associated with the overall survival in the training set (P≤0.01). Based on this six-lncRNA signature, the training-set patients could be classified into high-risk and low-risk subgroups with significantly different survival (HR=2.13, 95% CI=1.38-3.29; P=0.001). The prognostic value of this six-lncRNA signature was confirmed in the testing set and the two independent data sets. Further analysis revealed that the prognostic value of this signature was independent of age and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. The identification of the prognostic lncRNAs indicates the potential roles of lncRNAs in GBM pathogenesis. This six-lncRNA signature may have clinical implications in the subclassification of GBM.

摘要

长链非编码 RNA(lncRNA)代表了癌症研究的前沿,其与癌症的发生和预后有关。我们旨在鉴定具有胶质母细胞瘤(GBM)预后价值的 lncRNA 特征。使用 lncRNA 挖掘方法,我们对来自癌症基因组图谱(TCGA)的 213 个 GBM 肿瘤进行了 lncRNA 表达谱分析,这些肿瘤随机分为训练集(n=107)和测试集(n=106)。我们分析了训练集中 lncRNA 特征与临床结局之间的关联,并在测试集中验证了这些发现。我们还在来自基因表达综合数据库(GEO)的另外两个独立的 GBM 数据集中验证了鉴定出的 lncRNA 特征,这两个数据集分别包含了 68 例和 101 例患者的标本。我们确定了一组在训练集中与总生存期显著相关的六个 lncRNA(P≤0.01)。基于这个六-lncRNA 特征,训练集患者可以分为高风险和低风险亚组,两组的生存情况有显著差异(HR=2.13,95%CI=1.38-3.29;P=0.001)。该六-lncRNA 特征的预后价值在测试集和两个独立数据集得到了验证。进一步的分析表明,该特征的预后价值独立于年龄和 O-6-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)启动子甲基化状态。预后 lncRNA 的鉴定表明 lncRNA 在 GBM 发病机制中的潜在作用。该六-lncRNA 特征可能对 GBM 的亚分类具有临床意义。

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