Long Noncoding RNA Profiles Reveal Three Molecular Subtypes in Glioma
Long Noncoding RNA Profiles Reveal Three Molecular Subtypes in Glioma
复制标题
长非编码 RNA 谱揭示神经胶质瘤的三种分子亚型
DOI：
10.1111/cns.12220
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发表时间：
2014-04-01
影响因子：
5.5
通讯作者：
You, Yong-Ping
中科院分区：
文献类型：
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作者：
Li, Rui;Qian, Jin;You, Yong-Ping
背景胶质瘤是成人原发性脑肿瘤中致死率最高的一种。长链非编码RNA（LncRNA）参与多种肿瘤的发生发展，可能成为胶质瘤基因治疗的潜在靶点。方法和发现我们首先在伦勃朗数据集中利用一致性聚类法将胶质瘤分为LncR 1、LncR 2和LncR 3三种分子亚型。生存分析显示LncR 3亚型预后最好，而LncR 1亚型的总生存率最差。结果在独立的胶质瘤数据集GSE 16011中得到进一步验证。此外，我们收集并合并了两个数据库（伦勃朗和GSE 16011数据集）的数据，并分析了WHO II、III和IV型胶质瘤中各亚型的预后。得到了类似的结果。基因集变异分析（GSVA）结果表明，LncR 1亚型富集了培养星形胶质细胞的基因标签，而LncR 2亚型则具有神经元的基因标签。少突胶质细胞富含LncR 3。此外，在GSE 16011数据集中，IDH 1突变和1 p/19 q洛缺失均富含LncR 3，EGFR扩增在LncR 1中的比例较高。结论基于lncRNA表达谱的胶质瘤分子分类方法为胶质瘤基因治疗的进一步研究提供了一个潜在的平台，并为提高生存率提供了更个体化的治疗方法。
BackgroundGliomas are the most lethal type of primary brain tumor in adult. Long noncoding RNAs (lncRNAs), which are involved in the progression of various cancers, may offer a potential gene therapy target in glioma.Methods and FindingsWe first classified gliomas into three molecular subtypes (namely LncR1, LncR2 and LncR3) in Rembrandt dataset using consensus clustering. Survival analysis indicated that LncR3 had the best prognosis, while the LncR1 subtype showed the poorest overall survival rate. The results were further validated in an independent glioma dataset GSE16011. Additionally, we collected and merged data of the two databases (Rembrandt and GSE16011 dataset) and analyzed prognosis of each subtype in WHO II, III and IV gliomas. The similar results were obtained. Gene Set Variation Analysis (GSVA) demonstrated that LncR1 subtype enriched cultured astroglia's gene signature, while LncR2 subtype was characterized by neuronal gene signature. Oligodendrocytic was rich in LncR3. In addition, IDH1 mutation and 1p/19q LOH were found rich with LncR3, and EGFR amplification showed high percentage in LncR1 in GSE16011 dataset.ConclusionsWe report a novel molecular classification of glioma based on lncRNA expression profiles and believe that it would provide a potential platform for future studies on gene treatment for glioma and lead to more individualized therapies to improve survival rates.