Reconstruction of the Co-expression Network in Pediatric Low-grade Glioma

Brain tumors, in particular the central nervous system low-grade tumors, are the most common causes of death in children with brain cancers. A di↵erent genetic background was detected in children’s tumors compared to similar tumors in adults (۲,۵). Hence, in this study, we aimed to take a closer look at gene modules and signaling pathways related to pediatric low-grade Glioma using the Systems biology approaches. Methods:First, the raw RNA sequencing data of ۵۴ samples of pLGG (accession number: E-MTAB-۶۲۷۰) was collected from the ArrayExpress database. Based on the Galaxy online platform, a step-by-step RNAseq analysis was done to create an expression matrix (۱). The expression matrix was used as an input to the WGCNA package in R software to reconstruct the co-expression network and perform the module detection analysis. Then, hub genes of important modules were determined by the CHAT tool in Cytoscape software. At last, gProfiler was used for the functional enrichment analyses (۶).Results:Among the ۱۹ modules, ۲ modules including brown and turquoise modules showed the most association with Glioma. These two modules contain the most important genes previously reported as critical biomarkers in pLGG (۲-۵). The turquoise module includes IRS۱, MLST۸, FOXO۳, NLRC۵, and TRIM۶ hub genes, and the brown module contains LTBP۱ and SOSTDC۱ hub genes. The gene enrichment analysis regarding the signaling pathways ultimately led to the association of the Longevity regulating, mTOR signaling, PIP۳ activates AKT signaling pathways with these two modules and mainly Glioma tumors in children.Conclusion:Our results suggest new biomarkers in association with pLGG and their relation to some signaling pathways in tumor cells. The exact investigation of these genes among a vast number of genes in each critical signaling will result in developing potential therapeutic approaches.

کلیدواژه ها:

Pediatric Low-grade Glioma ، WGCNA ، Co-expression network ، Signaling pathway