Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, China.
Department of Ophthalmology, The First Hospital of Jilin University, Jilin University, Changchun, China.
J Comput Biol. 2020 May;27(5):718-728. doi: 10.1089/cmb.2019.0125. Epub 2019 Aug 28.
Glioblastoma (GBM) is a most aggressive primary cancer in brain with poor prognosis. This study aimed to identify novel tumor biomarkers with independent prognostic values in GBMs. The DNA methylation profiles were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus database. Differential methylated genes (DMGs) were screened from recurrent GBM samples using limma package in R software. Functional enrichment analysis was performed to identify major biological processes and signaling pathways. Furthermore, critical DMGs associated with the prognosis of GBM were screened according to univariate and multivariate cox regression analysis. A risk score-based prognostic model was constructed for these DMGs and prediction ability of this model was validated in training and validation data set. In total, 495 DMGs were identified between recurrent samples and disease-free samples, including 356 significantly hypermethylated and 139 hypomethylated genes. Functional and pathway items for these DMGs were mainly related to sensory organ development, neuroactive ligand-receptor interaction, pathways in cancer, etc. Five genes with abnormal methylation level were significantly correlated with prognosis according to survival analysis, such as , , , , and . Finally, the risk model provided an effective ability for prognosis prediction both in training and validation data set. We constructed a novel prognostic model for survival prediction of GBMs. In addition, we identified five DMGs as critical prognostic biomarkers in GBM progression.
胶质母细胞瘤(GBM)是一种最具侵袭性的脑部原发性癌症,预后不良。本研究旨在鉴定具有独立预后价值的 GBM 新型肿瘤标志物。从癌症基因组图谱和基因表达综合数据库中下载 DNA 甲基化图谱。使用 R 软件中的 limma 包从复发性 GBM 样本中筛选差异甲基化基因(DMGs)。进行功能富集分析以确定主要的生物学过程和信号通路。此外,根据单变量和多变量 Cox 回归分析筛选与 GBM 预后相关的关键 DMGs。根据这些 DMGs 构建风险评分预测模型,并在训练和验证数据集验证该模型的预测能力。总共在复发性样本和无疾病样本之间鉴定了 495 个 DMGs,包括 356 个明显高甲基化和 139 个低甲基化基因。这些 DMGs 的功能和途径项目主要与感觉器官发育、神经活性配体-受体相互作用、癌症途径等有关。根据生存分析,有 5 个异常甲基化水平的基因与预后显著相关,如、、、、和。最后,风险模型在训练和验证数据集均能有效预测预后。我们构建了一个用于 GBM 生存预测的新预后模型。此外,我们鉴定了 5 个 DMGs 作为 GBM 进展中的关键预后生物标志物。