Identification of aberrantly methylated-differentially expressed genes and potential agents for Ewing sarcoma

Human DNA methylation is a common epigenetic regulatory mechanism, and it plays a critical role in various diseases. However, the potential role of DNA methylation in Ewing sarcoma (ES) is not clear. This study aimed to explore the regulatory roles of DNA methylation in ES.

The microarray data of gene expression and methylation were downloaded from the 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, a protein-protein interaction (PPI) network was constructed, and hub genes were determined. Besides, a connectivity map (CMap) analysis was performed to screen bioactive compounds for ES treatment.

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. The PPI network analysis indicated C3, TF, and TCEB1 might serve as diagnostic and therapeutic targets of ES. Furthermore, CMap analysis revealed 6 chemicals as potential options for ES treatment.

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.