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.
Project description:Background:Understanding hub genes involved in gastric cancer (GC) metastasis could lead to effective approaches to diagnose and treat cancer. In this study, we aim to identify the hub genes and investigate the underlying molecular mechanisms of GC. Methods:To explore potential therapeutic targets for GC,three expression profiles (GSE54129, GSE33651, GSE81948) of the genes were extracted from the Gene Expression Omnibus (GEO) database. The GEO2R online tool was applied to screen out differentially expressed genes (DEGs) between GC and normal gastric samples. Database for Annotation, Visualization and Integrated Discovery was applied to perform Gene Ontology (GO) and KEGG pathway enrichment analysis. The protein-protein interaction (PPI) network of these DEGs was constructed using a STRING online software. The hub genes were identified by the CytoHubba plugin of Cytoscape software. Then, the prognostic value of these identified genes was verified by gastric cancer database derived from Kaplan-Meier plotter platform. Results:A total of 85 overlapped upregulated genes and 44 downregulated genes were identified. The majority of the DEGs were enriched in extracellular matrix organization, endodermal cell differentiation, and endoderm formation. Moreover, five KEGG pathways were significantly enriched, including ECM-receptor interaction, amoebiasis, AGE-RAGE signaling pathway in diabetic complications, focal adhesion, protein digestion and absorption. By combining the results of PPI network and CytoHubba, a total of nine hub genes including COL1A1, THBS1, MMP2, CXCL8, FN1, TIMP1, SPARC, COL4A1, and ITGA5 were selected. The Kaplan-Meier plotter database confirmed that overexpression levels of these genes were associated with reduced overall survival, except for THBS1 and CXCL8. Conclusions:Our study suggests that COL1A1, MMP2, FN1, TIMP1, SPARC, COL4A1, and ITGA5 may be potential biomarkers and therapeutic targets for GC. Further study is needed to assess the effect of THBS1 and CXCL8 on GC.
Project description:Glioblastoma multiforme (GBM) is a very serious mortality of central nervous system cancer. The microarray data from GSE2223, GSE4058, GSE4290, GSE13276, GSE68848 and GSE70231 (389 GBM tumour and 67 normal tissues) and the RNA-seq data from TCGA-GBM dataset (169 GBM and five normal samples) were chosen to find differentially expressed genes (DEGs). RRA (Robust rank aggregation) method was used to integrate seven datasets and calculate 133 DEGs (82 up-regulated and 51 down-regulated genes). Subsequently, through the PPI (protein-protein interaction) network and MCODE/ cytoHubba methods, we finally filtered out ten hub genes, including FOXM1, CDK4, TOP2A, RRM2, MYBL2, MCM2, CDC20, CCNB2, MYC and EZH2, from the whole network. Functional enrichment analyses of DEGs were conducted to show that these hub genes were enriched in various cancer-related functions and pathways significantly. We also selected CCNB2, CDC20 and MYBL2 as core biomarkers, and further validated them in CGGA, HPA and CCLE database, suggesting that these three core hub genes may be involved in the origin of GBM. All these potential biomarkers for GBM might be helpful for illustrating the important role of molecular mechanisms of tumorigenesis in the diagnosis, prognosis and targeted therapy of GBM cancer.
Project description:BACKGROUND This bioinformatics study aimed to identify differentially expressed genes (DEGs) and protein-protein interaction (PPI) networks associated with functional pathways in ulcerative colitis based on 3 Gene Expression Omnibus (GEO) datasets. MATERIAL AND METHODS The GSE87466, GSE75214, and GSE48958 MINiML formatted family files were downloaded from the GEO database. DEGs were identified from the 3 datasets, and volcano maps and heat maps were drawn after R language standardization and analysis, respectively. Venn diagram software was used to identify common DEGs. PPI analysis of common DEGs was performed using the Search Tool for the Retrieval of Interacting Genes. Gene modules and hub genes were visualized in the PPI network using Cytoscape. Enrichment analysis was performed for all common DEGs, module genes, and hub genes. RESULTS A total of 90 DEGs were selected, which included 3 functional modules and 1 hub gene module. CXCL8 module genes were mainly enriched in cytokine-mediated signaling pathways and interleukin (IL)-10 signaling. CCL20 module genes were mainly enriched in the IL-17 signaling pathway and cellular response to IL-1. Hub gene modules mainly involved IL-10, IL-4, and IL-13 signaling pathways. CXCL8, CXCL1, and IL-1ß were the top 3 hub genes and were mainly involved in IL-10 signaling. CONCLUSIONS Bioinformatics analysis using 3 GEO datasets identified CXCL8, CXCL1, and IL-1ß, which are involved in IL-10 signaling, as the top 3 hub genes in ulcerative colitis. The findings from this study remain to be validated, but they may contribute to the further understanding of the pathogenesis of ulcerative colitis.
Project description:BACKGROUND:Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide, exhibiting high morbidity and mortality. The prognosis of HNSCC patients has remained poor, though considerable efforts have been made to improve the treatment of this cancer. Therefore, identifying significant differentially expressed genes (DEGs) involved in HNSCC progression and exploiting them as novel biomarkers or potential therapeutic targets for HNSCC is highly valuable. METHODS:Overlapping differentially expressed genes (DEGs) were screened out from three independent gene expression omnibus (GEO) datasets and subjected to GO and kyoto encyclopedia of genes and genomes pathway enrichment analyses. The protein-protein interactions network of DEGs was constructed in the STRING database, and the top ten hub genes were selected using cytoHubba. The relative expression of hub genes was detected in GEPIA, Oncomine, and human protein atlas (HPA) databases. Furthermore, the relationship of hub genes with the overall survival and disease-free survival in HNSCC patients was investigated using the cancer genome atlas data. RESULTS:The top ten hub genes (SPP1, POSTN, COL1A2, FN1, IGFBP3, APP, MMP3, MMP13, CXCL8, and CXCL12) could be utilized as potential diagnostic indicators for HNSCC. The relative levels of FN1, APP, SPP1, and POSTN could be associated with the prognosis of HNSCC patients. The mRNA expression of APP and COL1A2 was validated in HNSCC samples. CONCLUSION:This study identified effective and reliable molecular biomarkers for diagnosis and prognosis by integrated bioinformatics analysis, suggesting novel and essential therapeutic targets for HNSCC.
Project description:Patients with Crohn's disease (CD) have a high risk of developing breast cancer, suggesting that there may be shared molecular mechanisms underlying CD and breast cancer. The purpose of the present study was to identify the critical genes and pathways underlying these molecular similarities using bioinformatics analysis. Publicly available microarray expression data from the Gene Expression Omnibus were analyzed, and a total of 53 overlapping differentially expressed genes (DEGs) between the CD (vs. controls) and breast cancer (vs. controls) groups were identified. These common DEGs were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Subsequently, a gene interaction network of the DEGs was constructed using Cytoscape software, with its plug-in cytoHubba and Molecular Complex Detection. The gene interaction network and module analysis demonstrated that prostaglandin G/H synthase 2, interleukin (IL)1? and CXCL8 were the major hub genes in the upregulated overlapping DEGs. The upregulated overlapping DEGs are found to be enriched in both the IL-17 and NF-kB signaling pathways. Taken together, the critical pathways and genes identified in the present study may help improve our understanding of why and how CD may contribute to the development of breast cancer.
Project description:BACKGROUND:Glioblastoma (GBM) has a high degree of malignancy, aggressiveness and recurrence rate. However, there are limited options available for the treatment of GBM, and they often result in poor prognosis and unsatisfactory outcomes. MATERIALS AND METHODS:In order to identify potential core genes in GBM that may provide new therapeutic insights, we analyzed three gene chips (GSE2223, GSE4290 and GSE50161) screened from the GEO database. Differentially expressed genes (DEG) from the tissues of GBM and normal brain were screened using GEO2R. To determine the functional annotation and pathway of DEG, Gene Ontology (GO) and KEGG pathway enrichment analysis were conducted using DAVID database. Protein interactions of DEG were visualized using PPI network on Cytoscape software. Next, 10 Hub nodes were screened from the differentially expressed network using MCC algorithm on CytoHubba software and subsequently identified as Hub genes. Finally, the relationship between Hub genes and the prognosis of GBM patients was described using GEPIA2 survival analysis web tool. RESULTS:A total of 37 up-regulated and 187 down-regulated genes were identified through microarray analysis. Amongst the 10 Hub genes selected, SV2B appeared to be the only gene associated with poor prognosis in glioblastoma based on the survival analysis. CONCLUSION:Our study suggests that high expression of SV2B is associated with poor prognosis in GBM patients. Whether SV2B can be used as a new therapeutic target for GBM requires further validation.
Project description:Glioblastoma (GBM), characterized by high morbidity and mortality, is one of the most common lethal diseases worldwide. To identify the molecular mechanisms that contribute to the development of GBM, three cohort profile datasets (GSE50161, GSE90598 and GSE104291) were integrated and thoroughly analyzed; these datasets included 57 GBM cases and 22 cases of normal brain tissue. The current study identified differentially expressed genes (DEGs), and analyzed potential candidate genes and pathways. Additionally, a DEGs-associated protein-protein interaction (PPI) network was established for further investigation. Then, the hub genes associated with prognosis were identified using a Kaplan-Meier analysis based on The Cancer Genome Atlas database. Firstly, the current study identified 378 consistent DEGs (240 upregulated and 138 downregulated). Secondly, a cluster analysis of the DEGs was performed based on functions of the DEGs and signaling pathways were analyzed using the enrichment analysis tool on DAVID. Thirdly, 245 DEGs were identified using PPI network analysis. Among them, two co-expression modules comprising of 30 and 27 genes, respectively, and 35 hub genes were identified using Cytoscape MCODE. Finally, Kaplan-Meier analysis of the hub genes revealed that the increased expression of calcium-binding protein 1 (CABP1) was negatively associated with relapse-free survival. To summarize, all enriched Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways may participate in mechanisms underlying GBM occurrence and progression, however further studies are required. CABP1 may be a key gene associated with the biological process of GBM development and may be involved in a crucial mechanism of GBM progression.
Project description:BACKGROUND Sepsis is an extremely common health issue with a considerable mortality rate in children. Our understanding about the pathogenic mechanisms of sepsis is limited. The aim of this study was to identify the differential expression genes (DEGs) in pediatric sepsis through comprehensive analysis, and to provide specific insights for the clinical sepsis therapies in children. MATERIAL AND METHODS Three pediatric gene expression profiles (GSE25504, GSE26378, GSE26440) were downloaded from the Gene Expression Omnibus (GEO) database. The difference expression genes (DEGs) between pediatric sepsis and normal control group were screened with the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed. Cytoscape with CytoHubba were used to identify the hub genes. Finally, NetworkAnalyst was used to construct the targeted microRNAs (miRNAs) of the hub genes. RESULTS Totally, 160 overlapping upward genes and 61 downward genes were identified. In addition, 5 KEGG pathways, including hematopoietic cell lineage, Staphylococcus aureus infection, starch and sucrose metabolism, osteoclast differentiation, and tumor necrosis factor (TNF) signaling pathway, were significantly enriched using a database for labeling, visualization, and synthetic discovery. In combination with the results of the protein-protein interaction (PPI) network and CytoHubba, 9 hub genes including ITGAM, TLR8, IL1ß, MMP9, MPO, FPR2, ELANE, SPI1, and C3AR1 were selected. Combined with DEG-miRNAs visualization, 5 miRNAs, including has-miR-204-5p, has-miR-211-5p, has-miR-590-5p, and has-miR-21-5p, were predicted as possibly the key miRNAs. CONCLUSIONS Our findings will contribute to identification of potential biomarkers and novel strategies for pediatric sepsis treatment.
Project description:Background:Myocardial infarction (MI) is the most terrible appearance of cardiovascular disease. The incidence of heart failure, one of the complications of MI, has increased in the past few decades. Therefore, the identification of MI from angina patients and the determination of new diagnoses and therapies of MI are increasingly important. The present study was aimed at identifying differentially expressed genes and miRNAs as biomarkers for the clinical and prognosis factors of MI compared with angina using microarray data analysis. Methods:Differentially expressed miRNAs and genes were manifested by GEO2R. The biological function of differentially expressed genes (DEGs) was examined by GO and KEGG. The construction of a protein-protein network was explored by STRING. cytoHubba was utilized to screen hub genes. Analysis of miRNA-gene pairs was executed by the miRWalk 3.0 database. The miRNA-target pairs overlapped with hub genes were seen as key genes. Logistic regressive analysis was performed by SPSS. Results:A number of 779 DEGs were recorded. The biological function containing extracellular components, signaling pathways, and cell adhesion was enriched. Twenty-four hub genes and three differentially expressed miRNAs were noted. Eight key genes were demonstrated, and 6 out of these 8 key genes were significantly related to clinical and prognosis factors following MI. Conclusions:CALCA, CDK6, MDM2, NRXN1, SOCS3, VEGFA, SMAD4, NCAM1, and hsa-miR-127-5p were thought to be potential diagnosis biomarkers for MI. Meanwhile, CALCA, CDK6, NRXN1, SMAD4, SOCS3, and NCAM1 were further identified to be potential diagnosis and therapy targets for MI.
Project description:Glioblastoma multiforme (GBM) is the most common and malignant brain tumor of the adult central nervous system and is associated with poor prognosis. The present study aimed to identify the hub genes in GBM in order to improve the current understanding of the underlying mechanism of GBM. The RNA?seq data were downloaded from The Cancer Genome Atlas database. The edgeR package in R software was used to identify differentially expressed genes (DEGs) between two groups: Glioblastoma samples and normal brain samples. Gene Ontology (GO) functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed using Database for Annotation, Visualization and Integrated Discovery software. Additionally, Cytoscape and Search Tool for the Retrieval of Interacting Genes/Proteins tools were used for the protein?protein interaction network, while the highly connected modules were extracted from this network using the Minimal Common Oncology Data Elements plugin. Next, the prognostic significance of the candidate hub genes was analyzed using UALCAN. In addition, the identified hub genes were verified by reverse transcription?quantitative (RT?q) PCR. In total, 1,483 DEGs were identified between GBM and control samples, including 954 upregulated genes and 529 downregulated genes (P<0.01; fold?change >16) and these genes were involved in different GO terms and signaling pathways. Furthermore, CDK1, BUB1, BUB1B, CENPA and GNG3 were identified as key genes in the GBM samples. The UALCAN tool verified that higher expression level of CENPA was relevant to poorer overall survival rates. In conclusion, CDK1, BUB1, BUB1B, CENPA and GNG3 were found to be potential biomarkers for GBM. Additionally, 'cell cycle' and '??aminobutyric acid signaling' pathways may serve a significant role in the pathogenesis of GBM.