The Study Of Gene Chips In Glioma Patients And Its Clinical Features And Prognosis

Objectives:By integrating bioinformatics to analyze gene expression profiles in GEO database and mRNAseq and clinical data in CGGA database,the differential genes,clinical traits and prognostic factors of glioma patients were discussed,and the molecular mechanism of glioma progression was further studied.Methods:In this study,a total of 1018 mRNAseq transcriptome Expression data and clinical data were downloaded from GEO database Expression profiling by array and Chinese glioma genome atlas CGGA database.The GEO2R online tool was used to analyze and screen the differential genes in the pathological tissues of normal tissues and glioma patients in GEO database.Genes related to clinical traits were screened from CGGA database,and the target genes with intersection were obtained by using Venn diagram.Kaplan-Meier(KM)analysis was performed to investigate the prognostic value of CHI3L2 expression.The area under ROC curve was used to evaluate the accuracy of the prediction.Wilcox test and Kruskal test were used to analyze the correlation between CHI3L2 and clinical characteristics,and the relevant genes were analyzed.PPI protein interaction network was established,and GO functional enrichment analysis and KEGG pathway enrichment analysis were used to explore the potential mechanism of differential genes.The drug target network was used to predict the therapeutic target of the selected core genes using the drug-bank database.R language package is used for statistics calculation and graphics rendering.Results:1.Among the genes with differences,274 up-regulated genes and 46 down-regulated genes were screened by GEO2R online tool analysis;Among them,PDPN,ABCC3,CHI3L2 and SERPINA3 are the common genes that have intersection with CGGA database.2.CHI3L2 is a differentially expressed gene in normal tissue and glioma tissue,and is lower in expression in glioma patients.In glioma patients,the high expression of CHI3L2 was significantly correlated with tumor recurrence,WHO grade,IDH mutation,and lp/19q combined deletion,all P<0.001.KM survival analysis showed that the 5-year survival rate of patients with high CHI3L2 expression was 21.3%,and the 95%confidence interval was 0.1724-0.264.The 5-year survival rate of patients with low expression was 57.5%and the 95%confidence interval was 0.523-0.633.Univariate independent prognostic analysis showed that high CHI3L2 expression was significantly associated with poor overall survival(OS)(risk ratio HR:1.225;95%confidence interval[CI]:1.185-1.267;P<0.001).Multivariate independent prognostic analysis showed that CHI3L2 was independently associated with overall survival(HR 1.066)(CI:1.026-1.107).P<0.001)and AUC>0.7.The first five genes positively correlated with CHI3L2 were SERPINA3,GBP2,IFI30,C1R and DENND2D,while the first five genes negatively correlated were OPHN1,CSMD3,RIMS2,SHANK2 and TUB.3.According to GO and KEGG enrichment analysis,DEGs were mainly concentrated in chemical synaptic transmission,neurotransmitter secretion,glutamate secretion,synaptic vesicle and learning response in the biological process(BP)group.In the CC group,the first 5 DEGs were enriched in the following order:cell junctions,dendrites,axons,synapses and cell membranes.In the molecular function(MF)group,DEGs were enriched in CA2+binding,GABA-A receptor activity,synaptic fusion protein-1 attachment,calmodulin binding,and extracellular ligand-gated ion channel activity.Enrichment analysis of KEGG signaling pathway showed that DEGs pathway was mainly concentrated in the signals of retrograde nerves,nicotine addiction,GABA synapses,morphine addiction,synaptic vesicle circulation,calcium signaling pathways,glutamate synapses,interaction in stimulating nerve tissues and cholinergic synapses.4.Drug target network analysis showed that GABRB3 was the main target gene of drugs labeled in drug-Bank.Conclusions:The expression of PDPN,ABCC3,CHI3L2 and SERPINA3 in glioma tissues was significantly lower than that in normal brain tissues,and the high expression of CHI3L2 in glioma patients may be a prognostic marker of poor glioma survival.The biological functions and pathways of the selected genes are related to neuromodulation,immune environment,extracellular matrix remodeling and other tumor microenvironments.GABA receptor function is one of the important factors affecting glioma,and GABRB3 may be a potential target for drug therapy.