GEO Database Screening Gliomas Related Markers And Clinical Significance Of ITGB2 And CXCR4 Protein In Gliomas

Objective:1.Large Scale Screening of specific biomarkers in gliomas based on online database methods and selection of prognostic molecular markers in gliomas.2.Exploring the differential expression of both Integrin beta-2(ITGB2)and C-X-C motif chemokine receptor 4(CXCR4)proteins in glioma and the clinical significance.Method:1.In order to screen glioma prognosis-related genes,three datasets GSE116520,GSE4290 and GSE15824 with glioma and normal brain tissues were downloaded from GEO database.After normalization,data correction and log2 conversion,the differential genes were screened by limma package of R program between glioma and control tissues.2.According to the screening criteria of differential expression gene sets(DEGs)that the absolute value of log2 FC is greater than 1 and adj.P.Value is less than 0.05,the differential expression gene sets of each data set are obtained,and the volcano and pheatmap are plotted.The intersection of the differential expression genes of each data set is obtained by using the online Venn diagrams webtool,and the co-expression differential gene sets(Co-DEGs)are obtained.3.GO and KEGG enrichment analysis were applied with the Co-DEGs.The differential gene set was used to explore the PPI network using STING database,and PPI network were used for visualization by Cytoscape software.Cytohubba plug-in was used to select the key genes for co-expression differential genes using Bottle Neck method.The top 10 genes were selected for further study.4.The top 10 genes were verified based on the TCGA database,and the survival curves of key genes were plotted to study their clinical significance.Combined with the research status of key genes in Pubmed database,the ITGB2 and CXCR4 gene was selected for clinical experiment verification.5.145 case paraffin samples of glioma samples and 20 case non-tumor samples(control)were selected to explore clinical significance of ITGB2 and CXCR4 proteins.At the same time,combined with the m RNA expression data of glioma in CGGA database,the expression of ITGB2 and CXCR4 proteins in glioma was comprehensively analyzed and the relationship between them and clinical parameters was evaluated.Results:1.A total of 2549 DEGs were identified in the data set GSE11650,including 1189up-regulated genes and 1360 down-regulated genes.A total of 2204 DEGs were selected from the GSE4290 dataset,there were 823 up-regulation genes and 1381down-regulated genes.Moreover,2122 DEGs were screened from the GSE15824 dataset.Among them,1130 genes were up-regulated and 992 genes were down-regulated.Finally,189 Co-DEGs were identified from the three datasets.2.GO enrichment consequences displayed that co-DEGs were chiefly focussed on the tumor-immune microenvironment related to antigen processing and presentation,opsin binding,macrophage activation and complement regulation.KEGG pathway results noticed that co-DEGs were principally concentrated on cell adhesion molecules,phagocytes,iron death,antigen processing and presentation and endocytosis.3.Top 10 key genes concerned to glioma were acquired by protein-protein interaction network analysis,which were KIF5 A,SCN2A,CXCR4,VCAM1,CP,ITGB2,HMOX1,HLA-DRA,CAV1 and VAMP8.Respectively,they were discrepantly expressed in glioma and correlated to the prognosis of patients with glioma.4.ITGB2 and CXCR4 proteins were highly expressed in glioma,and their expression levels increased with the increase of histological grade.Spearman correlation analysis showed that the expression of ITGB2 and CXCR4 was positively correlated.5.The consequence of clinical correlation analysis noticed that the expressions of ITGB2 and CXCR4 were remarkable correlated with IDH mutation,1p19 q deletion,age,WHO grade,MGMT promoter methylation and histological classification,but not with gender,tumor size and KPS score.6.The consequences of Kaplan-Meier survival analysis revealed that ITGB2 and CXCR4 protein expression levels,patients’ age,WHO grade and KPS score was an important survival predictor of patients with glioma.Cox regression analysis revealed that WHO grade,KPS score and the expression levels of ITGB2 and CXCR4 proteins were an individual dangerous divisors of the prognosis for patients with glioma.Conclusions:1.KIF5 A,SCN2A,CXCR4,VCAM1,CP,ITGB2,HMOX1,HLA-DRA,CAV1 and VAMP8 may be involved in the progression and prognosis of patients with glioma.2.Both ITGB2 and CXCR4 proteins were expressed in gliomas of different grades,and their expression levels were positively correlated with WHO grade.3.The expression of ITGB2 and CXCR4 was correlated with patients’ age and WHO grade,but not with patients’ gender,tumor size and KPS score.The expression of CXCR4 protein in human glioma was positively correlated with the protein of ITGB2,which may jointly affect the occurrence of glioma.4.The high expression of ITGB2 and CXCR4 proteins may be an independent risk factor for poor prognosis in human glioma patients.