journal homepage: www.elsevier.com/locate/heares
journal homepage: www.elsevier.com/locate/heares
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期刊主页：www.elsevier.com/locate/heares
DOI：
10.1016/j.wneu.2021.09.094
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发表时间：
2021
影响因子：
2
通讯作者：
E. Ku
中科院分区：
文献类型：
--
作者：
Jenny Wei;K. Johansen;C. McCulloch;M. Lipkowitz;M. Weir;Fengfei Lin;V. Campese;M. Smogorzewski;E. Ku
前庭神经鞘瘤是第三常见的颅内良性肿瘤，可偶发发生或与2型神经纤维瘤病（neurofibromatosis type 2 vestibular schwannoma [NF 2-VS]）合并发生。本研究的目的是提供一个全面的生物信息学分析的甲基化差异表达基因（MDEG）在NF 2-VS。（GSE 141801和GSE 108524）和基因甲基化微阵列（GSE 56598）用于鉴定和分析NF 2-VS中的MDEG。构建蛋白质-蛋白质相互作用（PPI）网络，并鉴定了hub基因和模块。最后，潜在的药物治疗靶向MDEGs提取NF 2-VS。结果共鉴定出57个高甲基化低表达基因和88个低甲基化高表达基因。与异常MDEG相关的通路包括P13 K-AKT、MAPK和Ras，它们也参与NF 2-VS。从PPI网络中鉴定出6个枢纽基因（EGFR、CCND 1、CD 53、CSF 1 R、PLAU和FGFR 1）。对上述基因的修饰改变了细胞间的通讯、对刺激的反应、细胞调节以及膜和蛋白质结合。结论MDEG的分析可以丰富对NF 2-VS发病机制的认识，为NF 2-VS潜在的生物标志物和治疗靶点奠定基础。
BackgroundVestibular schwannoma is the third most common benign intracranial tumor that can occur sporadically or be associated with neurofibromatosis type 2 (neurofibromatosis type 2 vestibular schwannoma [NF2-VS]). The aim of this study is to provide a comprehensive bioinformatic analysis of methylated-differentially expressed genes (MDEGs) in NF2-VS.MethodsTranscriptional sequencing datasets (GSE141801 and GSE108524) and gene methylation microarrays (GSE56598) from the Gene Expression Omnibus database were used to identify and analyze MDEGs in NF2-VS. A protein–protein interaction (PPI) network was built, and the hub genes and modules were identified. Finally, potential pharmacotherapy targeting MDEGs were extracted for NF2-VS.ResultsA total of 57 hypermethylation–low expression genes and 88 hypomethylation–high expression genes were identified. Pathways associated with aberrantly MDEGs included P13K-AKT, MAPK, and Ras, which were also involved in NF2-VS. Six hub genes (EGFR, CCND1, CD53, CSF1R, PLAU, and FGFR1) were identified from the PPI network. Modification of the aforementioned genes altered cell-to-cell communication, response to stimulus, cellular regulation, and membrane and protein bindings. Thirty drugs targeting these pathways were selected based on the hub genes.ConclusionsAnalysis of MDEGs may enrich the understanding of the molecular mechanisms of NF2-VS pathogenesis and lay the groundwork for potential biomarkers and therapeutic targets for NF2-VS.