High gene expression levels of VEGFA and CXCL8 in the peritumoral brain zone are associated with the recurrence of glioblastoma: A bioinformatics analysis

Abstract

The present study aimed to identify differentially regulated genes between the peritumoral brain zone (PBZ) and tumor core (TC) of glioblastoma (GBM), to elucidate the underlying molecular mechanisms and provide a target for the treatment of tumors. The GSE13276 and GSE116520 datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) for the PBZ and TC were obtained using the GEO2R tool. The bioinformatics and evolutionary genomics online tool Venn was used to identify common DEGs between the two datasets. The Database for Annotation, Visualization, and Integrated Discovery online tool was used to analyze enriched pathways of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The Search Tool for the Retrieval of Interacting Genes/Proteins online tool was used to construct a protein-protein interaction (PPI) network of DEGs. Hub genes were identified using Cytohubba, a plug-in for Cytoscape. The Gene Expression Profiling Interactive Analysis (GEPIA) database was utilized to perform survival analysis. In total, 75 DEGs, including 12 upregulated and 63 downregulated genes, were identified. In the GO term analysis, these DEGs were mainly enriched in ‘regulation of angiogenesis’ and ‘central nervous system development’. Furthermore, in the KEGG pathway analysis, the DEGs were mainly enriched in ‘bladder cancer’ and ‘endocytosis’. When filtering the results of the PPI network analysis using Cytohubba, a total of 10 hub genes, including proteolipid protein 1, myelin associated oligodendrocyte basic protein, contactin 2, myelin oligodendrocyte glycoprotein, myelin basic protein, myelin associated glycoprotein, SRY-box transcription factor 10, C-X-C motif chemokine ligand 8 (CXCL8), vascular endothelial growth factor A (VEGFA) and plasmolipin, were identified. These hub genes were further subjected to GO term and KEGG pathway analysis, and were revealed to be enriched in ‘central nervous system development’, ‘bladder cancer’ and ‘rheumatoid arthritis’. These hub genes were used to perform survival analysis using the GEPIA database, and it was determined that VEGFA and CXCL8 were significantly associated with a reduction in the overall survival of patients with GBM. In conclusion, the results suggest that the recurrence of GBM is associated with high gene expression levels VEGFA and CXCL8, and the development of the central nervous system.

Identification and analysis of key genes associated with acute myocardial infarction by integrated bioinformatics methods

“…The GO terms were comprised of 3 parts: cellular component (CC), biological process (BP), and molecular function (MF). [ 31 ] DEGs of BP were involved in neutrophil activation, neutrophil mediated immunity, response to molecule of bacterial origin, lipopolysaccharide, positive regulation of cytokine production, and cell activation. CC analysis revealed that DEGs were markedly enriched tertiary granule, secretory granule membrane, tertiary granule lumen, and cytoplasmic vesicle lumen.…”

Identification of Hub Genes and Key Pathways Associated with Anti-VEGF Resistant Glioblastoma Using Gene Expression Data Analysis

“…Temozolomide- resistant GBM shows high expression of TNFRSF12A and greater migratory capacity [ 29 ]. CXCL8/IL8 is a multifunctional cytokine which enhances the vascular permeability in GBM [ 30 , 31 ]; high expression of both VEGFA and CXCL8 can reduce the overall survival rate of GBM patients [ 32 ]. ADGRG1/GPR56 is a GPCR involved in adhesion signaling and HIF1A is a transcription factor, which has a critical role in GBM survival, resistance and invasion [ 33 ].…”

Identification of Key Genes with Clinical Outcome in Benign Meningioma Using Bioinformatic Analysis

“…CXCL8， also known as chemokine (C-X-C motif) ligand 8,plays a very important role in tumor growth、invasion and metastases in an autocrine and paracrine maner [43] .Some researches demonstrated that CXCL8 was associated with many types of tumors,such as glioblastoma 、 lung ademocarcinoma、 hepatocellular carcinoma and colon cancer [44][45][46] . Luo et al [44] demonstrated that high gene expression levels of CXCL8 and VEGF was correlating with recurrent glioblastoma.Daniel et al [47] showed that IL-8 was strongly associated with glioma formation and progression mediated by activator protein-1(AP-1) and nuclear transcription factor-kappa(NF-кB) site.…”

“…CXCL8， also known as chemokine (C-X-C motif) ligand 8,plays a very important role in tumor growth、invasion and metastases in an autocrine and paracrine maner [43] .Some researches demonstrated that CXCL8 was associated with many types of tumors,such as glioblastoma 、 lung ademocarcinoma、 hepatocellular carcinoma and colon cancer [44][45][46] . Luo et al [44] demonstrated that high gene expression levels of CXCL8 and VEGF was correlating with recurrent glioblastoma.Daniel et al [47] showed that IL-8 was strongly associated with glioma formation and progression mediated by activator protein-1(AP-1) and nuclear transcription factor-kappa(NF-кB) site. Liu et al [45] showed that CXCL8 was an independent unfavorable factor with recurrence free survival and overall survival in patients suffering from adenocarcinoma,and the human Dachshund homologue 1(DACH1) was able to antagonize CXCL8 through AP-1and NF-кB.Shen et al [46] reported that CXCL8 may induce tumor proliferation、invasiveness through induction of epithelial-mesenchymal transition via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B(AKT)/nuclear factor-кB(NF-кB) pathway.Researches demonstrated that human meningioma cells secreted specifically the CXC chemokine-8 [48,49] .In our study,the differential expression of CXCL8 between two datasets suggested it as a important target.…”