Integrated Analysis of Transcriptome and Differential Methylation of Neurofibromatosis Type 2 Vestibular Schwannomas.

Background: Vestibular 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.

Methods: Transcriptional 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.

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, 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.

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.