Identification of key methylation differentially expressed genes in posterior fossa ependymoma based on epigenomic and transcriptome analysis

Abstract

Background: Posterior fossa ependymoma (EPN-PF) can be classified into Group A posterior fossa ependymoma (EPN-PFA) and Group B posterior fossa ependymoma (EPN-PFB) according to DNA CpG island methylation profile status and gene expression. EPN-PFA usually occurs in children younger than 5 years and has a poor prognosis. Methods: Using epigenome and transcriptome microarray data, a multi-component weighted gene co-expression network analysis (WGCNA) was used to systematically identify the hub genes of EPN-PF. We downloaded two microarray datasets (GSE66354 and GSE114523) from the Gene Expression Omnibus (GEO) database. The Limma R package was used to identify differentially expressed genes (DEGs), and ChAMP R was used to analyze the differential methylation genes (DMGs) between EPN-PFA and EPN-PFB. GO and KEGG enrichment analyses were performed using the Metascape database. Results: GO analysis showed that enriched genes were significantly enriched in the extracellular matrix organization, adaptive immune response, membrane raft, focal adhesion, NF-kappa B pathway, and axon guidance, as suggested by KEGG analysis. Through WGCNA, we found that MEblue had a significant correlation with EPN-PF (R = 0.69, P = 1 × 10–08) and selected the 180 hub genes in the blue module. By comparing the DEGs, DMGs, and hub genes in the co-expression network, we identified five hypermethylated, lower expressed genes in EPN-PFA (ATP4B, CCDC151, DMKN, SCN4B, and TUBA4B), and three of them were confirmed by IHC. Conclusion: ssGSEA and GSVA analysis indicated that these five hub genes could lead to poor prognosis by inducing hypoxia, PI3K-Akt-mTOR, and TNFα-NFKB pathways. Further study of these dysmethylated hub genes in EPN-PF and the pathways they participate in may provides new ideas for EPN-PF treatment.