Dataset Information

Lymphocyte infiltration and key differentially expressed genes in the ulcerative colitis.

ABSTRACT: BACKGROUND:Ulcerative colitis (UC) was a type of inflammatory bowel diseases, which was difficult to cure and even would malignant turn into colon cancer. The specific etiology and molecular mechanism of UC were unclear to date. The purpose of this study was to search for new targets for the diagnosis and treatment of UC. METHODS:Firstly, we downloaded the gene expression data of UC from the gene expression omnibus database database (GSE107499), and used multiple bioinformatics methods to find differently expressed genes (DEGs) in UC. Subsequently, we evaluated the lymphocyte infiltration in UC inflamed colon tissue by using the cell type identification by estimating relative subset of known RNA transcripts method. RESULTS:We obtained 1175 DEGs and 8 hub genes (IL6, TNF, PTPRC, CXCL8, FN1, CD44, IL1B, and MMP9) in this study. Among them, 903 DEGs were up-regulated and 272 DEGs were down-regulated. Compared with non-inflamed colon tissues, the inflamed colon tissues had higher levels of memory B cells, activated memory CD4 T cells, follicular helper T cells, M1 macrophages, resting dendritic cells, activated dendritic cells, activated mast cells, and neutrophils, whereas the proportions of plasma cells, resting memory CD4 T cells, gamma delta T cells, activated NK cells, M2 macrophages and resting mast cells were relatively lower. CONCLUSIONS:The DEGs, hub genes and different lymphatic infiltration conditions can provide new targets for diagnosis and treatment of UC. However, these were just predictions through some theoretical methods, and more basic experiments will be needed to prove in the future.

SUBMITTER: Zhang J

PROVIDER: S-EPMC7458201 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lymphocyte infiltration and key differentially expressed genes in the ulcerative colitis.

Zhang Junhui J Shi Guixiu G

Medicine 20200801 35

<h4>Background</h4>Ulcerative colitis (UC) was a type of inflammatory bowel diseases, which was difficult to cure and even would malignant turn into colon cancer. The specific etiology and molecular mechanism of UC were unclear to date. The purpose of this study was to search for new targets for the diagnosis and treatment of UC.<h4>Methods</h4>Firstly, we downloaded the gene expression data of UC from the gene expression omnibus database database (GSE107499), and used multiple bioinformatics me ...[more]

PMID: 32871953

Similar Datasets

Project description:Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine whose cause and underlying mechanisms are not fully understood. The aim of this study was to use bioinformatics analysis to identify differentially expressed genes (DEGs) with diagnostic and therapeutic potential in UC. Materials and methods: Three UC datasets (GSE179285, GSE75214, GSE48958) were downloaded from the Gene Expression Omnibus (GEO) database. DEGs between normal and UC tissues were identified using the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed using Metascape. Protein-protein interaction network (PPI) analysis and visualization using STRING and Cytoscape. Finally, the miRNA gene regulatory network was constructed by Cytoscape to predict potential microRNAs (miRNAs) associated with DEGs. Results: A total of 446 DEGs were identified, consisting of 309 upregulated genes and 137 downregulated genes. The enriched functions and pathways of the DEGs include extracellular matrix, regulation of cell adhesion, inflammatory response, response to cytokine, monocarboxylic acid metabolic process, response to toxic substance. The analysis of KEGG pathway indicates that the DEGs were significantly enriched in Complement and coagulation cascades, Amoebiasis, TNF signaling pathway, bile secretion, and Mineral absorption. Combining the results of the PPI network and CytoHubba, 9 hub genes including CXCL8, ICAM1, CXCR4, CD44, IL1B, MMP9, SPP1, TIMP1, and HIF1A were selected. Based on the DEG-miRNAs network construction, 7 miRNAs including miR-335-5p, mir-204-5p, miR-93-5p, miR106a-5p, miR-21-5p, miR-146a-5p, and miR-155-5p were identified as potential critical miRNAs. Conclusion: In summary, we identified DEGs that may be involved in the progression or occurrence of UC. A total of 446 DEGs,9 hub genes and 7 miRNAs were identified, which may be considered as biomarkers of UC. Further studies, however, are needed to elucidate the biological functions of these genes in UC.

Project description:BackgroundUlcerative colitis (UC) is an inflammatory bowel disease that is difficult to diagnose and treat. To date, the degree of inflammation in patients with UC has mainly been determined by measuring the levels of nonspecific indicators, such as C-reactive protein and the erythrocyte sedimentation rate, but these indicators have an unsatisfactory specificity. In this study, we performed bioinformatics analysis using data from the National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) databases and verified the selected core genes in a mouse model of dextran sulfate sodium (DSS)-induced colitis.AimTo identify UC-related differentially expressed genes (DEGs) using a bioinformatics analysis and verify them in vivo and to identify novel biomarkers and the underlying mechanisms of UC.MethodsTwo microarray datasets from the NCBI-GEO database were used, and DEGs between patients with UC and healthy controls were analyzed using GEO2R and Venn diagrams. We annotated these genes based on their functions and signaling pathways, and then protein-protein interactions (PPIs) were identified using the Search Tool for the Retrieval of Interacting Genes. The data were further analyzed with Cytoscape software and the Molecular Complex Detection (MCODE) app. The core genes were selected and a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed. Finally, colitis model mice were established by administering DSS, and the top three core genes were verified in colitis mice using real-time polymerase chain reaction (PCR).ResultsOne hundred and seventy-seven DEGs, 118 upregulated and 59 downregulated, were initially identified from the GEO2R analysis and predominantly participated in inflammation-related pathways. Seven clusters with close interactions in UC formed: Seventeen core genes were upregulated [C-X-C motif chemokine ligand 13 (CXCL13), C-X-C motif chemokine receptor 2 (CXCR2), CXCL9, CXCL5, C-C motif chemokine ligand 18, interleukin 1 beta, matrix metallopeptidase 9, CXCL3, formyl peptide receptor 1, complement component 3, CXCL8, CXCL1, CXCL10, CXCL2, CXCL6, CXCL11 and hydroxycarboxylic acid receptor 3] and one was downregulated [neuropeptide Y receptor Y1 (NYP1R)] in the top cluster according to the PPI and MCODE analyses. These genes were substantially enriched in the cytokine-cytokine receptor interaction and chemokine signaling pathways. The top three core genes (CXCL13, NYP1R, and CXCR2) were selected and verified in a mouse model of colitis using real-time PCR Increased expression was observed compared with the control mice, but only CXCR2 expression was significantly different.ConclusionCore DEGs identified in UC are related to inflammation and immunity inflammation, indicating that these reactions are core features of the pathogenesis of UC. CXCR2 may reflect the degree of inflammation in patients with UC.

Project description:BackgroundUlcerative colitis-associated colorectal cancer (UC-CRC) is a life-threatening complication of ulcerative colitis (UC). The mechanisms underlying UC-CRC remain to be elucidated. The purpose of this study was to explore the key genes and biological processes contributing to colitis-associated dysplasia (CAD) or carcinogenesis in UC via database mining, thus offering opportunities for early prediction and intervention of UC-CRC.MethodsMicroarray datasets (GSE47908 and GSE87466) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between groups of GSE47908 were identified using the "limma" R package. Weighted gene co-expression network analysis (WGCNA) based on DEGs between the CAD and control groups was conducted subsequently. Functional enrichment analysis was performed, and hub genes of selected modules were identified using the "clusterProfiler" R package. Single-gene gene set enrichment analysis (GSEA) was conducted to predict significant biological processes and pathways associated with the specified gene.ResultsSix functional modules were identified based on 4929 DEGs. Green and blue modules were selected because of their consistent correlation with UC and CAD, and the highest correlation coefficient with the progress of UC-associated carcinogenesis. Functional enrichment analysis revealed that genes of these two modules were significantly enriched in biological processes, including mitochondrial dysfunction, cell-cell junction, and immune responses. However, GSEA based on differential expression analysis between sporadic colorectal cancer (CRC) and normal controls from The Cancer Genome Atlas (TCGA) indicated that mitochondrial dysfunction may not be the major carcinogenic mechanism underlying sporadic CRC. Thirteen hub genes (SLC25A3, ACO2, AIFM1, ATP5A1, DLD, TFE3, UQCRC1, ADIPOR2, SLC35D1, TOR1AIP1, PRR5L, ATOX1, and DTX3) were identified. Their expression trends were validated in UC patients of GSE87466, and their potential carcinogenic effects in UC were supported by their known functions and other relevant studies reported in the literature. Single-gene GSEA indicated that biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to angiogenesis and immune response were positively correlated with the upregulation of TFE3, whereas those related to mitochondrial function and energy metabolism were negatively correlated with the upregulation of TFE3.ConclusionsUsing WGCNA, this study found two gene modules that were significantly correlated with CAD, of which 13 hub genes were identified as the potential key genes. The critical biological processes in which the genes of these two modules were significantly enriched include mitochondrial dysfunction, cell-cell junction, and immune responses. TFE3, a transcription factor related to mitochondrial function and cancers, may play a central role in UC-associated carcinogenesis.

Dataset Information

Lymphocyte infiltration and key differentially expressed genes in the ulcerative colitis.

Publications

Lymphocyte infiltration and key differentially expressed genes in the ulcerative colitis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets