Integrated analysis of transcriptome and differential methylation of neurofibromatosis type 2 vestibular schwannomas

ABSTRACT Background Vestibular schwannoma (VS) is the third most common benign intracranial tumor that can occur sporadically (SVS) or be associated with neurofibromatosis type 2 (NF2-VS). The aim of this study is to provide a comprehensive bioinformatic analysis of methylated differentially expressed genes (MDEGs) in NF2-VS. Methods Transcriptional sequencing datasets (GSE141801, GSE108524) and gene methylation microarrays (GSE56598) from the Gene Expression Omnibus (GEO) database were employed 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. Results A total of 57 hypermethylation-low expression genes and 88 hypomethylation-high expression genes were identified. Pathways associated with aberrantly MDEGs included P13K-AKT, MAPK pathway and Ras, which were also involved in NF2-VS. Six hub genes namely, EGFR, CCND1, CD53, CSF1R, PLAU, and FGFR1 were identified from the PPI network. Modification of the above mentioned 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. Conclusions Analysis 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.