Screening of core driver genes and pathogenic high-risk signaling pathways in ependymoma

Abstract

Objective To screen the core-driving pathogenic genes in the occurrence and development of ependymoma (EPN), explore the involved signal pathways of its pathogenesis, and to clarify the relationship of prognosis with expression of these driver genes. Methods The differentially expressed gene (DEGs) were identified after comparing between gene expression profiles of the EPN tissues and normal tissues based on gene chip, microarray and bioinformatics. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analyses were conducted to find out the enrichment functions, pathways and hub genes. After hub genes were identified, the survival analysis of 325 patients, which data obtained from Chinese Glioma Genome Atlas (CCGA), were performed to clarify the relationship between prognosis and the expression levels of the hub genes. Results Genes TP53, TOP2A, CDK1, PCNA and ACTA2 were found as core driver genes, and their aberrant expression promoted the occurrence and development of EPN; Hedgehog signaling pathway, Notch signal pathway and mismatch repair signal pathway were the high-risk signal pathways for the development of EPN. And the results of survival analysis showed that the patients with lower expression of TOP2A, CDK1, PCNA and ACTA2 had favorable prognosis and longer progression-free survival (PFS) and overall survival (OS) (P < 0.05). Conclusion In this study, TP53, TOP2A, CDK1, PCNA and ACTA2 were selected as the core driver genes of ependymoma. At the same time, we explored the high-risk signaling pathways that cause EPN, and provided new targets for clinical diagnosis and treatment of EPN, which is of great significance.

Keywords

• ependymoma
• driver genes
• tumor
• molecular targeting therapy