Bioinformatics Analysis Identified Abnormal Methylated Differentially Expressed Genes In Glioblastoma

ObjectiveGBM(Glioblastoma)is one of the most common and most malignant brain tumors of the central nervous system in adults.With standard treatment of surgery,radiotherapy and chemotherapy,the median survival time of GBM is still less than 2 years and the prognosis is extremely poor,which is mainly related to the high invasiveness,chemotherapy-resistance and radiosurgery resistance.Therefore,it is urgently necessary to understand the in-depth pathogenesis of GBM and to screen out some diagnostic molecular markers and therapeutic molecular targets.DNA methylation,as an important mechanism of epigenetic modification,plays an important role in the occurrence and development of GBM.The purpose of this study was to screen out the abnormal methylated differentially expressed genes of GBM and the corresponding signaling pathways,to explore the potential mechanism of GBM occurrence and progress,and to find some prognosis related genesMethodThe GBM gene expression profile datebase and methylation database were retrieved,screened and downloaded from Gene Expression Omnibus(GEO)database,and Oncogenes and Tumor Suppressor Genes were obtained from Oncogenes and Tumor Suppressor Genes databases.Differential expression genes(DEGs)and Differential methylated genes(DMGs),Oncogenes and Tumor Suppressor Genes were analyzed and compared with each other using R software.The up-regulated hypomethylated genes and down-regulated hypomethylated genes were obtained from the intersections.DAVID was used to analyze the GO(Gene Ontology)and KEGG(Kyoto Encyclopedia of Genes and Genomes)pathways of the screened differential Genes.In Cytoscape software,use the STRING database construction of abnormal methylation differences gene protein interaction network PPI(protein,protein interaction),to identify low methylation increases respectively using MCODE plug-in gene and high methylation cut module,get module network diagram will interaction diagram,based on cytoHubba plug-in for protein interaction network diagram analysis,five methods are selected the top 10 genes,gene take intersection to get the final differences.The validation set obtained by GEO database was used to verify the screened genes,and then the identified genes were verified by cBioPortal,the relationship between gene expression and prognosis,the relationship between gene methylation and mRNA expression,and the change of differential genesResultGBM gene expression profile data sets GSE4290,GSE50161 and methylation profile data sets GSE79122 and GSE36278 were obtained from GEO database.GSE4290 and GSE79122 were used as training sets,and GSE50161 and GSE36278 as verification sets.Identified 429 low raised gene methylation,mainly in the process of biological enrichment in angiogenesis,the composition of extracellular matrix,immune response and inflammatory response,signal transduction,the molecular function of main enrichment in tumor necrosis factor(TNF)receptor activation,collagen protein,extracellular matrix(ECM)structure,as well as the combination of integrin,protein binding.The differentially expressed proto-oncogenes were CD44,Notch1,MMP9 and ITGB2.A total of 465 hypermethylated down-regulated genes were identified,which were mainly enriched in the positive regulation of excitatory postsynaptic potential,neurotransmitter secretion,potassium ion transport,nervous system development,chemical synaptic transmission,and voltage-gated potassium channel complex during the biological process.The molecular functions were mainly concentrated in extracellular ligand-gated ion channel activity,GABA-A receptor activity,potassium channel activity,delayed rectifying potassium channel activity,and voltage-gated potassium channel activity.Among the tumor suppressor genes with differential expression,there was DLG4ConclusionThis study has identified many genetic and epigenetic regulatory networks,providing an important basis for understanding the pathogenesis of GBM.The differentially expressed methylated gene CD44 in GBM was identified as a marker to determine the prognosis of GBM.Abnormal methylation of CD44,Notchl,MMP9,ITGB2 and DLG4 is an important mechanism for the occurrence and development of GBM.