scholarly journals Hub Genes Related to the Pathogenesis and Progression of Colorectal Cancer and Adenoma by Integrative Bioinformatics Approaches

2021 ◽  
Author(s):  
Yuxuan HUANG ◽  
Ge CUI
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Differentially Expressed Genes ◽  
Protein Interaction ◽  
Biological Networks ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Venn Diagram ◽  
Hub Genes ◽  
Protein Protein Interaction

Abstract Aims: To utilize the bioinformatics to analyze the differentially expressed genes (DEGs), interaction proteins, perform gene enrichment analysis, protein-protein interaction network (PPI) and map the hub genes between colorectal cancer(CRC) and colorectal adenocarcinomas(CA).Methods: We analyzed a microarray dataset (GSE32323 and GSE4183) from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in tumor tissues and non-cancerous tissues were identified using the dplyr and Venn diagram packages of the R Studio software. Functional annotation of the DEGs was performed using the Gene Ontology (GO) website. Pathway enrichment (KEGG) used the WebGestalt to analyze the data and R Studio to generate the graph. We constructed a protein–protein interaction (PPI) network of DEGs using STRING and Cytoscape software was used for visualization. Survival analysis of the hub genes and was performed using the online platform GEPIA to determine the prognostic value of the expression of hub genes in cell lines from CRC patients. The expression of molecules with prognostic values was validated on the UALCAN database. The expression of hub genes was examined using the Human Protein Atlas. Results: Applying the GEO2R analysis and R studio, we identified a total of 471 upregulated and 278 downregulated DEGs. By using the online database WebGestalt, we identified the most relevant biological networks involving DEGs with statistically significant differences in expression were mainly associated with biological processes involved in the cell proliferation, cell cycle transition, cell homeostasis and indicated the role of each DEGs in cell cycle regulation pathways. We found 10 hub genes with prognostic values were overexpressed in the CRC and CA samples.Conclusion: we found out ten hub genes and three core genes closely associated with the pathogenesis and prognosis of CRC and CA, which is of great significance for colorectal tumor early detection and prognosis evaluation.

scholarly journals Identification of differentially expressed genes between mucinous adenocarcinoma and other adenocarcinoma of colorectal cancer using bioinformatics analysis

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052094903
Author(s):  
Xue Zhang ◽  
Jing Zuo ◽  
Long Wang ◽  
Jing Han ◽  
Li Feng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Differentially Expressed Genes ◽  
Mucinous Adenocarcinoma ◽  
Wnt Signaling Pathway ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Venn Diagram ◽  
Bicarbonate Transport ◽  
Hub Genes

Objective As a unique histological subtype of colorectal cancer (CRC), mucinous adenocarcinoma (MC) has a poor prognosis and responds poorly to treatment. Genes and markers related to MC have not been reported. Methods To identify biomarkers involved in development of MC compared with other common adenocarcinoma (AC) subtypes, four datasets were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using GEO2R. A protein–protein interaction network was constructed. Functional annotation for DEGs was performed via DAVID, Metascape, and BiNGO. Significant modules and hub genes were identified using Cytoscape, and expression of hub genes and relationships between hub genes and MC were analyzed. Results The DEGs were mainly enriched in negative regulation of cell proliferation, bicarbonate transport, response to peptide hormone, cell–cell signaling, cell proliferation, and positive regulation of the canonical Wnt signaling pathway. The Venn diagram revealed eight significant hub genes: CXCL9, IDO1, MET, SNAI2, and ZEB2 were highly expressed in MC compared with AC, whereas AREG, TWIST1, and ZEB1 were expressed at a low level. AREG and MET might be significant biomarkers for MC. Conclusion The identified DEGs might help elucidate the pathogenesis of MC, identify potential targets, and improve treatment for CRC.

Extracting Biological Significant Subnetworks from Protein-Protein Interactions Induced by Differentially Expressed Genes of HIV-1 Vpr Variants

2015 ◽  
Vol 4 (4) ◽  
pp. 35-51 ◽  
Author(s):  
Bandana Barman ◽  
Anirban Mukhopadhyay
Keyword(s):  
Differentially Expressed Genes ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Wild Type ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Hiv 1

Identification of protein interaction network is very important to find the cell signaling pathway for a particular disease. The authors have found the differentially expressed genes between two sample groups of HIV-1. Samples are wild type HIV-1 Vpr and HIV-1 mutant Vpr. They did statistical t-test and found false discovery rate (FDR) to identify the genes increased in expression (up-regulated) or decreased in expression (down-regulated). In the test, the authors have computed q-values of test to identify minimum FDR which occurs. As a result they found 172 differentially expressed genes between their sample wild type HIV-1 Vpr and HIV-1 mutant Vpr, R80A. They found 68 up-regulated genes and 104 down-regulated genes. From the 172 differentially expressed genes the authors found protein-protein interaction network with string-db and then clustered (subnetworks) the PPI networks with cytoscape3.0. Lastly, the authors studied significance of subnetworks with performing gene ontology and also studied the KEGG pathway of those subnetworks.

scholarly journals Exploration and validation of related hub gene expression during SARS-CoV-2 infection of human bronchial organoids

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ke-Ying Fang ◽  
Wen-Chao Cao ◽  
Tian-Ao Xie ◽  
Jie Lv ◽  
Jia-Xin Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Protein Interaction ◽  
Social Order ◽  
Expression System ◽  
Differentially Expressed ◽  
Dimensional Structure ◽  
Hub Genes ◽  
R Software ◽  
Protein Protein Interaction

Abstract Background In the novel coronavirus pandemic, the high infection rate and high mortality have seriously affected people’s health and social order. To better explore the infection mechanism and treatment, the three-dimensional structure of human bronchus has been employed in a better in-depth study on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We downloaded a separate microarray from the Integrated Gene Expression System (GEO) on a human bronchial organoids sample to identify differentially expressed genes (DEGS) and analyzed it with R software. After processing with R software, Gene Ontology (GO) and Kyoto PBMCs of Genes and Genomes (KEGG) were analyzed, while a protein–protein interaction (PPI) network was constructed to show the interactions and influence relationships between these differential genes. Finally, the selected highly connected genes, which are called hub genes, were verified in CytoHubba plug-in. Results In this study, a total of 966 differentially expressed genes, including 490 upregulated genes and 476 downregulated genes were used. Analysis of GO and KEGG revealed that these differentially expressed genes were significantly enriched in pathways related to immune response and cytokines. We construct protein-protein interaction network and identify 10 hub genes, including IL6, MMP9, IL1B, CXCL8, ICAM1, FGF2, EGF, CXCL10, CCL2, CCL5, CXCL1, and FN1. Finally, with the help of GSE150728, we verified that CXCl1, CXCL8, CXCL10, CCL5, EGF differently expressed before and after SARS-CoV-2 infection in clinical patients. Conclusions In this study, we used mRNA expression data from GSE150819 to preliminarily confirm the feasibility of hBO as an in vitro model to further study the pathogenesis and potential treatment of COVID-19. Moreover, based on the mRNA differentiated expression of this model, we found that CXCL8, CXCL10, and EGF are hub genes in the process of SARS-COV-2 infection, and we emphasized their key roles in SARS-CoV-2 infection. And we also suggested that further study of these hub genes may be beneficial to treatment, prognostic prediction of COVID-19.

scholarly journals Exploring the Key Genes and Pathways in the Formation of Corneal Scar Using Bioinformatics Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Binfeng Liu ◽  
Ang Li ◽  
Hongbo Wang ◽  
Jialin Wang ◽  
Gongwei Zhai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Protein Interaction ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Signal Pathways ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Corneal Scar

The Corneal wound healing results in the formation of opaque corneal scar. In fact, millions of people around the world suffer from corneal scars, leading to loss of vision. This study aimed to identify the key changes of gene expression in the formation of opaque corneal scar and provided potential biomarker candidates for clinical treatment and drug target discovery. We downloaded Gene expression dataset GSE6676 from NCBI-GEO, and analyzed the Differentially Expressed Genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses, and protein-protein interaction (PPI) network. A total of 1377 differentially expressed genes were identified and the result of Functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) identification and protein-protein interaction (PPI) networks were performed. In total, 7 hub genes IL6 (interleukin-6), MMP9 (matrix metallopeptidase 9), CXCL10 (C-X-C motif chemokine ligand 10), MAPK8 (mitogen-activated protein kinase 8), TLR4 (toll-like receptor 4), HGF (hepatocyte growth factor), EDN1 (endothelin 1) were selected. In conclusion, the DEGS, Hub genes and signal pathways identified in this study can help us understand the molecular mechanism of corneal scar formation and provide candidate targets for the diagnosis and treatment of corneal scar.

scholarly journals Aberrantly hydroxymethylated differentially expressed genes and the associated protein pathways in osteoarthritis

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6425 ◽  
Author(s):  
Yang Fang ◽  
Pingping Wang ◽  
Lin Xia ◽  
Suwen Bai ◽  
Yonggang Shen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Ontology ◽  
Differentially Expressed Genes ◽  
Kegg Pathway ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Highly Expressed Genes ◽  
Protein Protein Interaction Network

Background The elderly population is at risk of osteoarthritis (OA), a common, multifactorial, degenerative joint disease. Environmental, genetic, and epigenetic (such as DNA hydroxymethylation) factors may be involved in the etiology, development, and pathogenesis of OA. Here, comprehensive bioinformatic analyses were used to identify aberrantly hydroxymethylated differentially expressed genes and pathways in osteoarthritis to determine the underlying molecular mechanisms of osteoarthritis and susceptibility-related genes for osteoarthritis inheritance. Methods Gene expression microarray data, mRNA expression profile data, and a whole genome 5hmC dataset were obtained from the Gene Expression Omnibus repository. Differentially expressed genes with abnormal hydroxymethylation were identified by MATCH function. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the genes differentially expressed in OA were performed using Metascape and the KOBAS online tool, respectively. The protein–protein interaction network was built using STRING and visualized in Cytoscape, and the modular analysis of the network was performed using the Molecular Complex Detection app. Results In total, 104 hyperhydroxymethylated highly expressed genes and 14 hypohydroxymethylated genes with low expression were identified. Gene ontology analyses indicated that the biological functions of hyperhydroxymethylated highly expressed genes included skeletal system development, ossification, and bone development; KEGG pathway analysis showed enrichment in protein digestion and absorption, extracellular matrix–receptor interaction, and focal adhesion. The top 10 hub genes in the protein–protein interaction network were COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL6A1, COL8A1, COL11A1, and COL24A1. All the aforementioned results are consistent with changes observed in OA. Conclusion After comprehensive bioinformatics analysis, we found aberrantly hydroxymethylated differentially expressed genes and pathways in OA. The top 10 hub genes may be useful hydroxymethylation analysis biomarkers to provide more accurate OA diagnoses and target genes for treatment of OA.

scholarly journals SLC1A1, SLC16A9, and CNTN3 Are Potential Biomarkers for the Occurrence of Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Jie Zhou ◽  
Zhiman Xie ◽  
Ping Cui ◽  
Qisi Su ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ulcerative Colitis ◽  
Differentially Expressed Genes ◽  
Colorectal Adenoma ◽  
Immune Cells ◽  
Interaction Network ◽  
Diagnostic Value ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
Hub Genes

Background. This study is aimed at identifying unknown clinically relevant genes involved in colorectal cancer using bioinformatics analysis. Methods. Original microarray datasets GSE107499 (ulcerative colitis), GSE8671 (colorectal adenoma), and GSE32323 (colorectal cancer) were downloaded from the Gene Expression Omnibus. Common differentially expressed genes were filtered from the three datasets above. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed, followed by construction of a protein-protein interaction network to identify hub genes. Kaplan-Meier survival analysis and TIMER database analysis were used to screen the genes related to the prognosis and tumour-infiltrating immune cells of colorectal cancer. Receiver operating characteristic curves were used to assess whether the genes could be used as markers for the diagnosis of ulcerative colitis, colorectal adenoma, and colorectal cancer. Results. A total of 237 differentially expressed genes common to the three datasets were identified, of which 60 were upregulated, 125 were downregulated, and 52 genes that were inconsistently up- and downregulated. Common differentially expressed genes were mainly enriched in the cellular component of extracellular exosome and integral component of membrane categories. Eight hub genes, i.e., CXCL3, CXCL8, CEACAM7, CNTN3, SLC1A1, SLC16A9, SLC4A4, and TIMP1, were related to the prognosis and tumour-infiltrating immune cells of colorectal cancer, and these genes have diagnostic value for ulcerative colitis, colorectal adenoma, and colorectal cancer. Conclusion. Three novel genes, CNTN3, SLC1A1, and SLC16A9 were shown to have diagnostic value with respect to the occurrence of colorectal cancer and should be verified in future studies.

scholarly journals Bioinformatics Analysis and Identification of Potential Biomarkers in Gastric Cancer

2020 ◽  
Author(s):  
Jingdi Yang ◽  
Bo Peng ◽  
Xianzheng Qin ◽  
Tian Zhou
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Differentially Expressed Genes ◽  
Bioinformatics Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Protein Protein Interaction Network

Abstract Background: Although the morbidity and mortality of gastric cancer are declining, gastric cancer is still one of the most common causes of death. Early detection of gastric cancer is of great help to improve the survival rate, but the existing biomarkers are not sensitive to diagnose early gastric cancer. The aim of this study is to identify the novel biomarkers for gastric cancer.Methods: Three gene expression profiles (GSE27342, GSE63089, GSE33335) were downloaded from Gene Expression Omnibus database to select differentially expressed genes. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were performed to explore the biological functions of differentially expressed genes. Cytoscape was utilized to construct protein-protein interaction network and hub genes were analyzed by plugin cytoHubba of Cytoscape. Furthermore, Gene Expression Profiling Interactive Analysis and Kaplan-Meier plotter were used to verify the identified hub genes.Results: 35 overlapping differentially expressed genes were screened from gene expression datasets, which consisted of 11 up-regulated genes and 24 down-regulated genes. Gene Ontology functional enrichment analysis revealed that differentially expressed genes were significantly enriched in digestion, regulation of biological quality, response to hormone and steroid hormone, and homeostatic process. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed differentially expressed genes were enriched in the secretion of gastric acid and collecting duct acid, leukocyte transendothelial migration and ECM-receptor interaction. According to protein-protein interaction network, 10 hub genes were identified by Maximal Clique Centrality method.Conclusion: By using bioinformatics analysis, COL1A1, BGN, THY1, TFF2 and SST were identified as the potential biomarkers for early detection of gastric cancer.

scholarly journals Comprehensive analysis of an lncRNA-miRNA-mRNA competing endogenous RNA network in pulpitis

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7135 ◽  
Author(s):  
Fangcao Lei ◽  
Han Zhang ◽  
Xiaoli Xie
Keyword(s):  
Differentially Expressed Genes ◽  
Protein Interaction ◽  
Dental Pulp ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Regulatory Relationship ◽  
Protein Protein Interaction ◽  
Qrt Pcr ◽  
Ppi Networks

Background Pulpitis is a common inflammatory disease that affects dental pulp. It is important to understand the molecular signals of inflammation and repair associated with this process. Increasing evidence has revealed that long noncoding RNAs (lncRNAs), via competitively sponging microRNAs (miRNAs), can act as competing endogenous RNAs (ceRNAs) to regulate inflammation and reparative responses. The aim of this study was to elucidate the potential roles of lncRNA, miRNA and messenger RNA (mRNA) ceRNA networks in pulpitis tissues compared to normal control tissues. Methods The oligo and limma packages were used to identify differentially expressed lncRNAs and mRNAs (DElncRNAs and DEmRNAs, respectively) based on expression profiles in two datasets, GSE92681 and GSE77459, from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were further analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein–protein interaction (PPI) networks and modules were established to screen hub genes using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and the Molecular Complex Detection (MCODE) plugin for Cytoscape, respectively. Furthermore, an lncRNA-miRNA-mRNA-hub genes regulatory network was constructed to investigate mechanisms related to the progression and prognosis of pulpitis. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify critical lncRNAs that may significantly affect the pathogenesis in inflamed and normal human dental pulp. Results A total of 644 upregulated and 264 downregulated differentially expressed genes (DEGs) in pulpitis samples were identified from the GSE77459 dataset, while 8 up- and 19 downregulated probes associated with lncRNA were identified from the GSE92681 dataset. Protein–protein interaction (PPI) based on STRING analysis revealed a network of DEGs containing 4,929 edges and 623 nodes. Upon combined analysis of the constructed PPI network and the MCODE results, 10 hub genes, including IL6, IL8, PTPRC, IL1B, TLR2, ITGAM, CCL2, PIK3CG, ICAM1, and PIK3CD, were detected in the network. Next, a ceRNA regulatory relationship consisting of one lncRNA (PVT1), one miRNA (hsa-miR-455-5p) and two mRNAs (SOCS3 and PLXNC1) was established. Then, we constructed the network in which the regulatory relationship between ceRNA and hub genes was summarized. Finally, our qRT-PCR results confirmed significantly higher levels of PVT1 transcript in inflamed pulp than in normal pulp tissues (p = 0.03). Conclusion Our study identified a novel lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of pulpitis.

scholarly journals Key Genes and Prognostic Analysis in HER2+ Breast Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382098329
Author(s):  
Yujie Weng ◽  
Wei Liang ◽  
Yucheng Ji ◽  
Zhongxian Li ◽  
Rong Jia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Protein Interaction ◽  
Differentially Expressed ◽  
Protein Kinase Activity ◽  
Protein Protein Interaction ◽  
Risk Of Death ◽  
Her2 Breast Cancer ◽  
Key Genes

Human epidermal growth factor 2 (HER2)+ breast cancer is considered the most dangerous type of breast cancers. Herein, we used bioinformatics methods to identify potential key genes in HER2+ breast cancer to enable its diagnosis, treatment, and prognosis prediction. Datasets of HER2+ breast cancer and normal tissue samples retrieved from Gene Expression Omnibus and The Cancer Genome Atlas databases were subjected to analysis for differentially expressed genes using R software. The identified differentially expressed genes were subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses followed by construction of protein-protein interaction networks using the STRING database to identify key genes. The genes were further validated via survival and differential gene expression analyses. We identified 97 upregulated and 106 downregulated genes that were primarily associated with processes such as mitosis, protein kinase activity, cell cycle, and the p53 signaling pathway. Visualization of the protein-protein interaction network identified 10 key genes ( CCNA2, CDK1, CDC20, CCNB1, DLGAP5, AURKA, BUB1B, RRM2, TPX2, and MAD2L1), all of which were upregulated. Survival analysis using PROGgeneV2 showed that CDC20, CCNA2, DLGAP5, RRM2, and TPX2 are prognosis-related key genes in HER2+ breast cancer. A nomogram showed that high expression of RRM2, DLGAP5, and TPX2 was positively associated with the risk of death. TPX2, which has not previously been reported in HER2+ breast cancer, was associated with breast cancer development, progression, and prognosis and is therefore a potential key gene. It is hoped that this study can provide a new method for the diagnosis and treatment of HER2 + breast cancer.

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