Identification of Potential Key Genes in the Pathogenesis of Chronic Obstructive Pulmonary Disease Through Bioinformatics Analysis.
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ABSTRACT:
SUBMITTER: Guan Q
PROVIDER: S-EPMC8595135 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Objective: Ferroptosis has an important role in developing pulmonary fibrosis. The present project aimed to identify and validate the potential ferroptosis-related genes in pulmonary fibrosis by bioinformatics analyses and experiments. Methods: First, the pulmonary fibrosis tissue sequencing data were obtained from Gene Expression Omnibus (GEO) and FerrDb databases. Bioinformatics methods were used to analyze the differentially expressed genes (DEGs) between the normal control group and the pulmonary fibrosis group and extract ferroptosis-related DEGs. Hub genes were screened by enrichment analysis, protein-protein interaction (PPI) analysis, and random forest algorithm. Finally, mouse pulmonary fibrosis model was made for performing an exercise intervention and the hub genes' expression was verified through qRT-PCR. Results: 13 up-regulated genes and 7 down-regulated genes were identified as ferroptosis-related DEGs by comparing 103 lung tissues with idiopathic pulmonary fibrosis (IPF) and 103 normal lung tissues. PPI results indicated the interactions among these ferroptosis-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment and Genome-Ontology (GO) enrichment analyses showed that these ferroptosis-related genes involved in the organic anion transport, response to hypoxia, response to decrease oxygen level, HIF-1 signaling pathway, renal cell carcinoma, and arachidonic acid metabolism signaling pathway. The confirmed genes using PPI analysis and random forest algorithm included CAV1, NOS2, GDF15, HNF4A, and CDKN2A. qRT-PCR of the fibrotic lung tissues from the mouse model showed that the mRNA levels of NOS2 and GDF15 were up-regulated, while CAV1 and CDKN2A were down-regulated. Also, treadmill training led to an increased expression of CAV1 and CDKN2A and a decrease in the expression of NOS2 and GDF15. Conclusion: Using bioinformatics analysis, 20 potential genes were identified to be associated with ferroptosis in pulmonary fibrosis. CAV1, NOS2, GDF15, and CDKN2A were demonstrated to be influencing the development of pulmonary fibrosis by regulating ferroptosis. These findings suggested that, as an aerobic exercise treatment, treadmill training reduced ferroptosis in the pulmonary fibrosis tissues, and thus, reduces inflammation in the lungs. Aerobic exercise training initiate concomitantly with induction of pulmonary fibrosis reduces ferroptosis in lung. These results may develop our knowledge about pulmonary fibrosis and may contribute to its treatment.
| S-EPMC8770739 | biostudies-literature
Project description:BackgroundChronic obstructive pulmonary disease (COPD) is one of the major cause of global death. The purpose of our analysis was to detect a more reliable biomarker and small-molecule drug candidates and to identify the precise mechanisms involved in COPD.MethodsThree data sets were downloaded from the Gene Expression Omnibus database and analysed by Gene Expression Omnibus 2R. Functional enrichment analyses were performed by Metascape. We use the STRING data to build a protein-protein interaction network. The targets of differentially expressed microRNA (DE miRNA) were predicted by the miRWalk database. Small-molecule drugs were predicted on connectivity map.ResultsA total of 181 differentially expressed genes and 35 DE miRNAs were confirmed. The protein-protein interaction network including all integrated differentially expressed genes was constructed, and 4 modules were filtrated. The module genes were relative to immune, inflammatory and oxidative stress functions according to a pathway analysis. The top 20 key genes were screened. Among the DE miRNAs found to be regulating key genes, miR-194-3p, MiR-502-5p, MiR-5088-5p, MiR-3127-5p, and miR-23a-5p might be the most significant due to their high number of connecting nodes in COPD. In addition, cephaeline, emetine, gabapentin, and amrinone were found to be potential drugs to treat COPD patients.ConclusionOur study suggests that miR-194-3p, miR-502-5p, and miR-23a-5p might participate in the nosogenesis of COPD. In addition, 4 potential small-molecule drugs were considered potentially useful for treating COPD patients.
| S-EPMC8601278 | biostudies-literature
Project description:It is essential to assess the cancer risk for patients with chronic obstructive pulmonary disease (COPD). Comparing gene expression data from patients with lung cancer (a total of 506 samples) and those with cancer-adjacent normal lung tissues (a total of 370 samples), we generated a qualitative transcriptional signature consisting of 2046 gene pairs. The signature was verified in an evaluation dataset comprising 18 subjects with severe disease and 52 subjects with moderate disease (Wilcoxon rank-sum test; p = 7.33 × 10-5). Similar results were obtained in other independent datasets. Among the gene pairs in the signature, 326 COPD stage-related gene pairs were identified based on Spearman's rank correlation tests and those gene pairs comprised 368 unique genes. Of these 368 genes, 16 genes were significantly dysregulated in COPD rat model data compared with control data. Some of these genes (Dhx16, Upf2, Notch3, Sec61a1, Dyrk2, and Hmmr) were altered when the COPD rat model was treated with traditional Chinese medicines (TCM), including Bufei Yishen formula, Bufei Jianpi formula, and Yiqi Zishen formula. Overall, the signature could predict the cancer incidence-risk of COPD and the identified key genes might provide guidance regarding both the treatment of COPD using TCM and the prevention of cancer in patients with COPD. KEY MESSAGESA cancer risk assessment signature was identified in patients with COPD.The signature is insensitive to batch effects and is well verified.COPD key genes identified in this study might play a crucial role in TCM treatment and cancer prevention.
| S-EPMC9415445 | biostudies-literature
Project description:ObjectivesChronic obstructive pulmonary disease (COPD) is characterized by lung inflammation and remodeling. Macrophage polarization is associated with inflammation and tissue remodeling, as well as immunity. Therefore, this study attempts to investigate the diagnostic value and regulatory mechanism of macrophage polarization-related genes for COPD by bioinformatics analysis and to provide a new theoretical basis for experimental research.MethodsThe raw gene expression profile dataset (GSE124180) was collected from the Gene Expression Omnibus (GEO) database. Next, a weighted gene coexpression network analysis (WGCNA) was conducted to screen macrophage polarization-related genes. The differentially expressed genes (DEGs) between the COPD and normal samples were generated using DESeq2 v3.11 and overlapped with the macrophage polarization-related genes. Moreover, functional annotations of overlapped genes were conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resource. The immune-related genes were selected, and their correlation with the differential immune cells was analyzed by Pearson. Finally, receiver operating characteristic (ROC) curves were used to verify the diagnostic value of genes.ResultsA total of 4922 coexpressed genes related to macrophage polarization were overlapped with the 203 DEGs between the COPD and normal samples, obtaining 25 genes related to COPD and macrophage polarization. GEM, S100B, and GZMA of them participated in the immune response, which were considered the candidate biomarkers. GEM and S100B were significantly correlated with marker genes of B cells which had a significant difference between the COPD and normal samples. Moreover, GEM was highly associated with the genes in the PI3K/Akt/GSK3β signaling pathway, regulation of actin cytoskeleton, and calcium signaling pathway based on a Pearson correlation analysis of the candidate genes and the genes in the B cell receptor signaling pathway. PPI network analysis also indicated that GEM might participate in the regulation of the PI3K/Akt/GSK3β signaling pathway. The ROC curve showed that GEM possessed an excellent accuracy in distinguishing COPD from normal samples.ConclusionsThe data provide a transcriptome-based evidence that GEM is related to COPD and macrophage polarization likely contributes to COPD diagnosis. At the same time, it is hoped that in-depth functional mining can provide new ideas for exploring the COPD pathogenesis.
| S-EPMC8238569 | biostudies-literature
Project description:This study was designed to identify the potential key protein interaction networks, genes, and correlated pathways in early-onset colorectal cancer (CRC) via bioinformatics methods. We selected microarray data GSE4107 consisting 12 patient's colonic mucosa and 10 healthy control mucosa; initially, the GSE4107 were downloaded and analyzed using limma package to identify differentially expressed genes (DEGs). A total of 131 DEGs consisting of 108 upregulated genes and 23 downregulated genes of patients in early-onset CRC were selected by the criteria of adjusted P values <.01 and |log2 fold change (FC)| ≥ 2. The gene ontology functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were accomplished to view the biological process, cellular components, molecular function, and the KEGG pathways of DEGs. Finally, protein-protein interactions (PPIs) were constructed, and the hub protein module was identified. Genes such as ACTA2, ACTG2, MYH11, CALD1, MYL9, TPM2, and LMOD1 were strongly implicated in CRC. In summary, in this study, we indicated that molecular mechanisms were involved in muscle contraction and vascular smooth muscle contraction signaling pathway, which improve our understanding of CRC and could be used as new therapeutic targets for CRC.
| S-EPMC6383095 | biostudies-literature
Project description:Esophageal adenocarcinoma (EAC) is the predominant pathological subtype of esophageal cancer in Europe and the USA. The present bioinformatics study analyzed a high-throughput sequencing dataset, GSE94869, to determine differentially expressed genes (DEGs) in order to identify key genes, biological processes and pathways associated with EAC. Functional enrichment analysis was performed using the Database for Annotation Visualization and Integrated Discovery. The co-expression network of the DEGs was established using Weighted Gene Co-Expression Network Analysis and visualized using Cytoscape. A Kaplan-Meier analysis based on The Cancer Genome Atlas (TCGA) database was used to identify prognosis-associated genes. Univariate and multivariate Cox proportional hazard models were used to identify genes with a prognostic value regarding relapse-free survival (RFS), while validation of the differential expression of prognosis-associated genes was performed using a box plot based on data from TCGA and another microarray dataset, GSE26886. A total of 130 DEGs, comprising 82 upregulated and 48 downregulated genes, were identified. The upregulated DEGs were significantly associated with extracellular matrix organization, disassembly, and the phosphoinositide-3 kinase/AKT, Rap1 and Ras signaling pathways, while the downregulated genes were associated with the Wnt signalling pathway. Subsequently, two co-expression modules were established and 20 hub genes were identified. The blue module was associated with the Rap1 signaling pathway, while the turquoise module was associated with the Ras and Rap1 signaling pathways. Among them, methyltransferase like 7B (METTL7B) was associated with RFS. Furthermore, the overexpression of METTL7B in EAC was successfully validated using data from TCGA and GSE26886. The present study identified key genes and provides potential biomarkers for the diagnosis and treatment of EAC.
| S-EPMC6781836 | biostudies-literature
Project description:PurposeChronic obstructive pulmonary disease (COPD) is a major cause of death and morbidity worldwide. A better understanding of new biomarkers for COPD patients and their complex mechanisms in the progression of COPD are needed.MethodsAn algorithm was conducted to reveal the proportions of 22 subsets of immune cells in COPD samples. Differentially expressed immune-related genes (DE-IRGs) were obtained based on the differentially expressed genes (DEGs) of the GSE57148 dataset, and 1509 immune-related genes (IRGs) were downloaded from the ImmPort database. Functional enrichment analyses of DE-IRGs were conducted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and Ingenuity Pathway Analysis (IPA). We defined the DE-IRGs that had correlations with immune cells as hub genes. The potential interactions among the hub genes were explored by a protein-protein interaction (PPI) network.ResultsThe CIBERSORT results showed that lung tissue of COPD patients contained a greater number of resting NK cells, activated dendritic cells, and neutrophils than normal samples. However, the fractions of follicular helper T cells and resting dendritic cells were relatively lower. Thirty-eight DE-IRGs were obtained for further analysis. Functional enrichment analysis revealed that these DE-IRGs were significantly enriched in several immune-related biological processes and pathways. Notably, we also observed that DE-IRGs were associated with the coronavirus disease COVID-19 in the progression of COPD. After correlation analysis, six DE-IRGs associated with immune cells were considered hub genes, including AHNAK, SLIT2 TNFRRSF10C, CXCR1, CXCR2, and FCGR3B.ConclusionIn the present study, we investigated immune-related genes as novel diagnostic biomarkers and explored the potential mechanism for COPD based on CIBERSORT analysis, providing a new understanding for COPD treatment.
| S-EPMC8742581 | biostudies-literature
Project description:BackgroundChronic obstructive pulmonary disease (COPD) is prevalent mainly in older adults, especially those who are smokers. It appears to be regulated by multiple genes, but there is some degree of familial clustering. The evidence to date suggests that COPD-associated biomarkers are largely inadequate for disease diagnosis, so we conducted a comprehensive search for more specific genetic markers.MethodsWe used 3 datasets from the Gene Expression Omnibus (GEO) database. By investigating the biological information [i.e., Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and weighted gene co-expression network analysis (WGCNA)], we filtered out 8 differentially expressed genes (DEGs) and validated the transcript levels of those hub genes in 16HBE cell lines, THP-1 cell lines and lung tissue of COPD patients.ResultsThe 8 hub genes comprised amyloid precursor protein (APP), fibronectin 1, insulin-like growth factor 1 (IGF1), β-actin, capping actin protein of muscle Z-line subunit alpha 2, secreted phosphoprotein 1 (SPP1), catalase (CAT), and colony stimulating factor 2 (CSF2) were selected from among the DEGs. Cigarette smoke extract-stimulated 16HBE cells were found to highly express SPP1, CSF2, and IGF1. In addition, IGF1 levels were increased and IGF1 and APP levels were decreased in CSE-stimulated THP-1 cells. SPP1 and FN1 showed increased expression levels in lung tissue of COPD patients, but the opposite held for APP and CAT.ConclusionsWe identified 8 hub genes of COPD based on GO, KEGG and WGCNA, which have provided insights into the pathophysiological mechanisms of COPD.
| S-EPMC9279780 | biostudies-literature
Project description:Intracerebral hemorrhage (ICH) is a dangerous neurological disease. The mechanism of ferroptosis in ICH remains unclear. Using bioinformatics analysis, we aimed to identify the key molecules involved in ferroptosis and provide treatment targets for ICH to further explore the mechanism of ferroptosis in ICH. GSE24265 was downloaded from the Gene Expression Omnibus (GEO) dataset and intersected with ferroptosis genes. A total of 45 differentially expressed genes (DEGs) were selected, most of which were involved in the TNF signaling pathway and oxidative stress response. Key modules constructed by the protein-protein interaction (PPI) network analysis and screening of genes related to the TNF signaling pathway led to the confirmation of the following genes of interest: MAPK1, MAPK8, TNFAIP3, ATF4, and SLC2A1. Moreover, MAPK1 was one of the key genes related to TNF signaling and oxidative stress, and it may play an important role in ferroptosis after cerebral hemorrhage. The MAPK1-related molecules included hsa-miR-15b-5P, hsa-miR-93-5P, miR-20b-5p, SNHG16, XIST, AC084219.4, RP11-379K17.11, CTC-444N24.11, GS1-358P8.4, CTB-89H12.4, RP4-773N10.5, and FGD5-AS1. We also generated a hemorrhage rat model, which was used to conduct exercise intervention in ICH rats, and qRT-PCR was used to assess the expression levels of our genes of interest. The mRNA levels after cerebral hemorrhage showed that MAPK1, ATF4, SLC2A1, and TNFAIP3 were upregulated, whereas MAPK8 was downregulated. Treadmill training increased the expression of anti-inflammatory molecules TNFAIP3 and SLC2A1 and reduced the expression of MAPK1, ATF4, and MAPK8, indicating that treadmill training may be utilized as antioxidant therapy to decrease neuronal ferroptosis. The results of this study indicated that the MAPK1-related mRNA-miRNA-lncRNA interaction chain could be potentially employed as a biomarker of the inception and progression of ferroptosis after cerebral hemorrhage.
| S-EPMC8215678 | biostudies-literature
Project description:Clear cell renal cell carcinoma (CCRCC) is a typical type of RCC with the worst prognosis among the common epithelial neoplasms of the kidney. However, its molecular pathogenesis remains unknown. Therefore, the aim of the present study was to screen for effective and potential pathogenic biomarkers of CCRCC. The gene expression profile of the GSE16441, GSE36895, GSE40435, GSE46699, GSE66270 and GSE71963 datasets were downloaded from the Gene Expression Omnibus database. First, the limma package in R language was used to identify differentially expressed genes (DEGs) in each dataset. The robust and strong DEGs were explored using the robust rank aggregation method. A total of 980 markedly robust DEGs were identified (429 upregulated and 551 downregulated). According to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, these DEGs exhibited an obvious enrichment in various cancer-related biological pathways and functions. The Search Tool for the Retrieval of Interacting Genes/Proteins database was used for the construction of a protein-protein interaction (PPI) network, the Cytoscape MCODE plug-in for module analysis and the cytoHubba plug-in to identify hub genes from the aforementioned DEGs. A total of four key modules were identified in the PPI network. A total of six hub genes, including C-X-C motif chemokine ligand 12, bradykinin receptor B2, adenylate cyclase 7, calcium sensing receptor (CASR), kininogen 1 and lysophosphatidic acid receptor 5, were identified. The DEG results of the hub genes were verified using The Cancer Genome Atlas database, and CASR was found to be significantly associated with the prognosis of patients with CCRCC. In conclusion, the present study provided new insight and potential biomarkers for the diagnosis and prognosis of CCRCC.
| S-EPMC7377202 | biostudies-literature