Specific Glioma Prognostic Subtype Distinctions Based on DNA Methylation Patterns

Specific Glioma Prognostic Subtype Distinctions Based on DNA Methylation Patterns
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基于 DNA 甲基化模式的特定神经胶质瘤预后亚型区分

DOI:
10.3389/fgene.2019.00786
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发表时间:
2019-09-12
影响因子:
3.7
通讯作者:
Fang, Zhiyou
Fang, Zhiyou
中科院分区:
生物学3区
文献类型:
--
作者:
Chen, Xueran;Zhao, Chenggang;Fang, Zhiyou

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DNA methylation is an important regulator of gene expression and may provide an important basis for effective glioma diagnosis and therapy. Here, we explored specific prognosis subtypes based on DNA methylation status using 653 gliomas from The Cancer Genome Atlas (TCGA) database. Five subgroups were distinguished by consensus clustering using 11,637 cytosines preceding a guanosine (CpGs) that significantly influenced survival. The specific DNA methylation patterns were correlated with age, tumor stage, and prognosis. Additionally, weighted gene co-expression network analysis (WGCNA) analysis of CpG sites revealed that 11 of them could distinguish the samples into high- and low-methylation groups and could classify the prognostic information of samples after cluster analysis of the training set samples using the hierarchical clustering algorithm. Similar results were obtained from the test set and 12 glioma patients. Moreover, in vitro experiments revealed an inverse relationship between methylation level and migration ability or insensitivity to temozolomide (or radiotherapy) of glioma cells based on the final prognostic predictor. Thus, these results suggested that the model constructed in this study could provide guidance for clinicians regarding the prognosis of various epigenetic subtypes.