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