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整合多层次分子数据推断胶质母细胞瘤和低级别胶质瘤之间的区别。

Integrating multiple-level molecular data to infer the distinctions between glioblastoma and lower-grade glioma.

机构信息

Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China.

Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

出版信息

Int J Cancer. 2019 Aug 15;145(4):952-961. doi: 10.1002/ijc.32174. Epub 2019 Feb 11.

DOI:10.1002/ijc.32174
PMID:30694558
Abstract

Glioblastomas (GBMs) and lower-grade gliomas (LGGs) are the most common malignant brain tumors. Despite extensive studies that have suggested that there are differences between the two in terms of clinical profile and treatment, their distinctions on a molecular level had not been systematically analyzed. Here, we investigated the distinctions between GBM and LGG based on multidimensional data, including somatic mutations, somatic copy number variants (SCNVs), gene expression, lncRNA expression and DNA methylation levels. We found that GBM patients had a higher mutation frequency and SCNVs than LGG patients. Differential mRNAs and lncRNAs between GBM and LGG were identified and a differential mRNA-lncRNA network was constructed and analyzed. We also discovered some differential DNA methylation sites could distinguish between GBM and LGG samples. Finally, we identified some key GBM- and LGG-specific genes featuring multiple-level molecular alterations. These specific genes participate in diverse functions; moreover, GBM-specific genes are enriched in the glioma pathway. Overall, our studies explored the distinctions between GMB and LGG using a comprehensive genomics approach that may provide novel insights into studying the mechanism and treatment of brain tumors.

摘要

胶质母细胞瘤(GBMs)和低级别胶质瘤(LGGs)是最常见的恶性脑肿瘤。尽管有大量研究表明,这两种肿瘤在临床特征和治疗方面存在差异,但它们在分子水平上的区别尚未得到系统分析。在这里,我们基于多维数据(包括体细胞突变、体细胞拷贝数变异(SCNVs)、基因表达、lncRNA 表达和 DNA 甲基化水平)研究了 GBM 和 LGG 之间的区别。我们发现 GBM 患者的突变频率和 SCNVs 高于 LGG 患者。鉴定出 GBM 和 LGG 之间的差异表达 mRNA 和 lncRNA,并构建和分析了差异表达的 mRNA-lncRNA 网络。我们还发现了一些差异 DNA 甲基化位点可以区分 GBM 和 LGG 样本。最后,我们鉴定了一些具有多层次分子改变的关键 GBM 和 LGG 特异性基因。这些特定基因参与多种功能;此外,GBM 特异性基因富集在神经胶质瘤通路中。总的来说,我们使用全面的基因组学方法研究了 GMB 和 LGG 之间的区别,这可能为研究脑肿瘤的机制和治疗提供新的思路。

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Comprehensive Transcriptomic Analysis and Experimental Validation Identify lncRNA HOXA-AS2/miR-184/COL6A2 as the Critical ceRNA Regulation Involved in Low-Grade Glioma Recurrence.综合转录组分析与实验验证确定lncRNA HOXA-AS2/miR-184/COL6A2为参与低级别胶质瘤复发的关键ceRNA调控机制。
Onco Targets Ther. 2020 Jun 3;13:4999-5016. doi: 10.2147/OTT.S245896. eCollection 2020.
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Overexpression of Gene is a Favorable Prognostic Marker in Lower-Grade Gliomas and Predicts a Favorable Outcome in Patients with Mutations and Chromosome 1p19q Codeletion.
基因的过表达是低级别胶质瘤的一个良好预后标志物,并可预测具有突变和1p19q染色体共缺失的患者的良好结局。
Cancers (Basel). 2019 Dec 18;12(1):13. doi: 10.3390/cancers12010013.