Identification of Aberrantly Methylated-differentially Expressed Genes and Potential Agents for Ewing’s Sarcoma

Abstract Background: DNA methylation is a common epigenetic regulatory way, and it plays a critical role in various human diseases. However, the potential role of how DNA methylation impacts Ewing’s sarcoma (ES) is not clear. This study aimed to explore the regulatory role of DNA methylation in ES.Methods: The microarray data of gene expression and methylation were downloaded from Gene Expression Omnibus (GEO) database, and analyzed via GEO2R. Venn analysis was then applied to identify aberrantly methylated differentially expressed genes (DEGs). Subsequently, Function and pathway enrichment analysis was conducted. Protein-protein interaction (PPI) network was constructed. Hub genes were determined. Besides, a connectivity map (CMap) analysis was performed to screen bioactive compounds for ES treatment.Results: A total of 135 hypomethylated high expression genes and 523 hypermethylated low expression genes were identified. The hypomethylated high expression genes were enriched in signal transduction and the apoptosis process. Meanwhile, hypermethylated low expression genes were related to DNA replication and transcription regulation. We next determined 10 hub genes through PPI analysis, among them, C3, TF, and TCEB1 might serve as diagnostic and therapeutic targets. Furthermore, CMap analysis revealed 6 chemicals as potential options for ES treatment. Conclusions: For the first time, we jointly analyzed gene profiling and methylation data about ES. The introduction of DNA methylation characteristics over DEGs is helpful to understand the pathogenesis of ES. The identified hub aberrantly methylated DEGs and chemicals might provide some novel insights on ES treatment.