scholarly journals Identification of differentially expressed genes, signaling pathways and immune infiltration in rheumatoid arthritis by integrated bioinformatics analysis

Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Yanzhi Ge ◽  
Li Zhou ◽  
Zuxiang Chen ◽  
Yingying Mao ◽  
Ting Li ◽  
...  

Abstract Background The disability rate associated with rheumatoid arthritis (RA) ranks high among inflammatory joint diseases. However, the cause and potential molecular events are as yet not clear. Here, we aimed to identify differentially expressed genes (DEGs), pathways and immune infiltration involved in RA utilizing integrated bioinformatics analysis and investigating potential molecular mechanisms. Materials and methods The expression profiles of GSE55235, GSE55457, GSE55584 and GSE77298 were downloaded from the Gene Expression Omnibus database, which contained 76 synovial membrane samples, including 49 RA samples and 27 normal controls. The microarray datasets were consolidated and DEGs were acquired and further analyzed by bioinformatics techniques. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed using R (version 3.6.1) software, respectively. The protein-protein interaction (PPI) network of DEGs were developed utilizing the STRING database. Finally, the CIBERSORT was used to evaluate the infiltration of immune cells in RA. Results A total of 828 DEGs were recognized, with 758 up-regulated and 70 down-regulated. GO and KEGG pathway analyses demonstrated that these DEGs focused primarily on cytokine receptor activity and relevant signaling pathways. The 30 most firmly related genes among DEGs were identified from the PPI network. The principal component analysis showed that there was a significant difference between the two tissues in infiltration immune. Conclusion This study shows that screening for DEGs, pathways and immune infiltration utilizing integrated bioinformatics analyses could aid in the comprehension of the molecular mechanisms involved in RA development. Besides, our study provides valuable data related to DEGs, pathways and immune infiltration of RA and may provide new insight into the understanding of molecular mechanisms.

2020 ◽  
Author(s):  
Yanzhi Ge ◽  
Li Zhou ◽  
Zuxiang Chen ◽  
Yingying Mao ◽  
Ting Li ◽  
...  

Abstract Background: The disability rate associated with rheumatoid arthritis (RA) ranks high among inflammatory joint diseases. However, the cause and potential molecular events are as yet not clear. Here, we aimed to identify differentially expressed genes (DEGs), pathways and immune infiltration involved in RA utilizing integrated bioinformatics analysis and investigating potential molecular mechanisms. Materials and methods: The expression profiles of GSE55235, GSE55457, GSE55584 and GSE77298 were downloaded from the Gene Expression Omnibus database, which contained 76 synovial membrane samples, including 49 RA samples and 27 normal controls. The microarray datasets were consolidated and DEGs were acquired and further analyzed by bioinformatics techniques. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed using R (version 3.6.1) software, respectively. The protein-protein interaction (PPI) network of DEGs were developed utilizing the STRING database. Finally, the CIBERSORT was used to evaluate the infiltration of immune cells in RA. Results: A total of 828 DEGs were recognized, with 758 up-regulated and 70 down-regulated. GO and KEGG pathway analyses demonstrated that these DEGs focused primarily on cytokine receptor activity and relevant signaling pathways. The 30 most firmly related genes among DEGs were identified from the PPI network. The principal component analysis showed that there was a significant difference between the two tissues in infiltration immune. Conclusion: This study shows that screening for DEGs, pathways and immune infiltration utilizing integrated bioinformatics analyses could aid in the comprehension of the molecular mechanisms involved in RA development. Besides, our study provides valuable data related to DEGs, pathways and immune infiltration of RA and may provide new insight into the understanding of molecular mechanisms.


2020 ◽  
Author(s):  
Yanzhi Ge ◽  
Li Zhou ◽  
Zuxiang Chen ◽  
Yingying Mao ◽  
Ting Li ◽  
...  

Abstract Background The disability rate associated with rheumatoid arthritis (RA) ranks high among inflammatory joint diseases. However, the cause and potential molecular events are as yet not clear. Here, we aimed to identify key genes and pathways involved in RA utilizing integrated bioinformatics analysis and uncover underlying molecular mechanisms. Materials and methods The expression profiles of GSE55235, GSE55457, GSE55584 and GSE77298 were downloaded from the Gene Expression Omnibus database, which contained 76 synovial membrane samples, including 49 RA samples and 27 controls. The microarray datasets were consolidated and differentially expressed genes (DEGs) were acquired and further analyzed by bioinformatics techniques. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed using R (version 3.6.1), respectively. The protein-protein interaction (PPI) networks of DEGs were developed utilizing the STRING database. Results A total of 828 DEGs were recognized, with 758 up-regulated and 70 down-regulated. GO and KEGG pathway analyses demonstrated that these DEGs focused primarily on multifactorial binding, transcription activity, cytokin-cytokin receptor interaction and relevant signaling pathways. The 30 most firmly related genes among DEGs were identified from the PPI network. Conclusion This study shows that screening for DEGs and pathways utilizing integrated bioinformatics analyses could aid in the comprehension of the molecular mechanisms involved in RA development. In addition, our study provides valuable data for the effective prevention, diagnosis, treatment and rehabilitation of RA patients as well as providing potential targets for the treatment of RA.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Shumei Tang ◽  
Xiangcheng Xiao

Abstract Background and Aims Diabetes has considerable negative impact on morbidity and mortality and causes huge social and economic burden. As one of the most serious microvascular complication of diabetes, diabetic nephropathy (DN) leads to a large population of end-stage renal disease in many countries. The pathogenesis of DN is always a hot topic and the underlying molecular events are not completely clear. Tubular injury plays an important role and may be the initial event. Although few therapeutic treatments could postpone the onset and development, the morbidity of DN remains high. More available therapeutic treatments are urgently needed as well as early stage diagnostic markers and more credible prognostic molecular markers. As a wide range application of high-throughput omics technology, various public network database platforms have included extensive transcriptomics data for deeper bioinformatics analysis. Integrating these data provides better understandings of molecular functions and biological processes. We performed integrated bioinformatics to recognize differentially expressed genes and discussed potential molecular mechanisms in DN. Method The expression profiles of GSE30529, GSE47184, GSE99325 and GSE104954 were downloaded from the Gene Expression Omnibus database. The four microarray datasets were centralized, integrated and performed a difference analysis. Next, differentially expressed genes (DEGs) were deeply analyzed by gene ontology annotation and enrichment analysis. STRING database was used to conducted a PPI network and Molecular Complex Detection (MCODE) software was used to identify central genes. Results The four files contain 63 tubular biopsy samples from patients with DN and 41 control tubule samples. We identified 18 target DEGs, C3, PROM1, LUM, CPA3, SERPINA3, ANXA1, CX3CR1, AGR2, CD48, REG1A, RARRES1, CYP24A1, C1R, CFB, CDH6, PVALB, GADD45B and KLK1. GO analysis indicated that biological processes of DEGs concentrate on proteolysis, inflammatory response, complement activation and regulation of complement activation. Main cellular components include extracellular exosome, extracellular region, extracellular space, blood microparticle, protein complex and plasma membrane. Molecular functions include calcium ion binding and serine-type endopeptidase activity. DEGs were found that maybe mainly involved in staphylococcus aureus infection, renin-angiotensin system, and complement and coagulation cascades by KEGG pathway analysis. The PPI network of DEGs were established by STRING database and one significant modules were identified by MCODE software. In addition, 3 hub genes, C3, CX3CR1 and ANXA1, were discerned from the PPI network. Conclusion To better clarify the underlying molecular mechanisms and provide more effective targets, this study screened DEGs and pathways in DN using bioinformatics analyses.


Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Haoming Li ◽  
Linqing Zou ◽  
Jinhong Shi ◽  
Xiao Han

Abstract Background Alzheimer’s disease (AD) is a fatal neurodegenerative disorder, and the lesions originate in the entorhinal cortex (EC) and hippocampus (HIP) at the early stage of AD progression. Gaining insight into the molecular mechanisms underlying AD is critical for the diagnosis and treatment of this disorder. Recent discoveries have uncovered the essential roles of microRNAs (miRNAs) in aging and have identified the potential of miRNAs serving as biomarkers in AD diagnosis. Methods We sought to apply bioinformatics tools to investigate microarray profiles and characterize differentially expressed genes (DEGs) in both EC and HIP and identify specific candidate genes and pathways that might be implicated in AD for further analysis. Furthermore, we considered that DEGs might be dysregulated by miRNAs. Therefore, we investigated patients with AD and healthy controls by studying the gene profiling of their brain and blood samples to identify AD-related DEGs, differentially expressed miRNAs (DEmiRNAs), along with gene ontology (GO) analysis, KEGG pathway analysis, and construction of an AD-specific miRNA–mRNA interaction network. Results Our analysis identified 10 key hub genes in the EC and HIP of patients with AD, and these hub genes were focused on energy metabolism, suggesting that metabolic dyshomeostasis contributed to the progression of the early AD pathology. Moreover, after the construction of an miRNA–mRNA network, we identified 9 blood-related DEmiRNAs, which regulated 10 target genes in the KEGG pathway. Conclusions Our findings indicated these DEmiRNAs having the potential to act as diagnostic biomarkers at an early stage of AD.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11203
Author(s):  
Dingyu Chen ◽  
Chao Li ◽  
Yan Zhao ◽  
Jianjiang Zhou ◽  
Qinrong Wang ◽  
...  

Aim Helicobacter pylori cytotoxin-associated protein A (CagA) is an important virulence factor known to induce gastric cancer development. However, the cause and the underlying molecular events of CagA induction remain unclear. Here, we applied integrated bioinformatics to identify the key genes involved in the process of CagA-induced gastric epithelial cell inflammation and can ceration to comprehend the potential molecular mechanisms involved. Materials and Methods AGS cells were transected with pcDNA3.1 and pcDNA3.1::CagA for 24 h. The transfected cells were subjected to transcriptome sequencing to obtain the expressed genes. Differentially expressed genes (DEG) with adjusted P value < 0.05, — logFC —> 2 were screened, and the R package was applied for gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The differential gene protein–protein interaction (PPI) network was constructed using the STRING Cytoscape application, which conducted visual analysis to create the key function networks and identify the key genes. Next, the Kaplan–Meier plotter survival analysis tool was employed to analyze the survival of the key genes derived from the PPI network. Further analysis of the key gene expressions in gastric cancer and normal tissues were performed based on The Cancer Genome Atlas (TCGA) database and RT-qPCR verification. Results After transfection of AGS cells, the cell morphology changes in a hummingbird shape and causes the level of CagA phosphorylation to increase. Transcriptomics identified 6882 DEG, of which 4052 were upregulated and 2830 were downregulated, among which q-value < 0.05, FC > 2, and FC under the condition of ≤2. Accordingly, 1062 DEG were screened, of which 594 were upregulated and 468 were downregulated. The DEG participated in a total of 151 biological processes, 56 cell components, and 40 molecular functions. The KEGG pathway analysis revealed that the DEG were involved in 21 pathways. The PPI network analysis revealed three highly interconnected clusters. In addition, 30 DEG with the highest degree were analyzed in the TCGA database. As a result, 12 DEG were found to be highly expressed in gastric cancer, while seven DEG were related to the poor prognosis of gastric cancer. RT-qPCR verification results showed that Helicobacter pylori CagA caused up-regulation of BPTF, caspase3, CDH1, CTNNB1, and POLR2A expression. Conclusion The current comprehensive analysis provides new insights for exploring the effect of CagA in human gastric cancer, which could help us understand the molecular mechanism underlying the occurrence and development of gastric cancer caused by Helicobacter pylori.


2021 ◽  
Author(s):  
Churen Zhang ◽  
Ruoran Sun

Abstract Background. Among the diseases of oral mucosa, oral lichen planus (OLP) is characterized by chronic autoimmune/autoinflammation. However, the etiology and pathogenesis of OLP were still limited. The aim of this research was to identify the differentially expressed genes and their potentially interacted miRNAs in OLP to provide a possible explanation of the pathogenesis of OLP and therapeutic biomarkers.Methods. The OLP microarray dataset (GSE52130) was download from the Gene Expression Omnibus (GEO) database. R software was used to identify differentially expressed genes between the OLP samples and normal oral mucosa. Functional enrichment analysis of DEGs, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, were conducted. Protein–protein interaction (PPI) network analysis was performed in the STRING database. CytoHubba in the Cytoscape software was applied to determining the top 10 hub genes, whose relative miRNA was identified through RNA Interactome Database.Results. Overall, 627 DEGs was identified in OLP samples, including 351 highly expressed genes and 276 lowly expressed genes. GO analysis indicated that the epidermal differentiation was mostly enriched. For the KEGG pathway, the DEGs in OLP samples were mostly involved in Staphylococcus aureus infection, Estrogen signaling pathway, Serotonergic synapse and Histidine metabolism. Top 10 hub genes including LOR, LCE3D, LCE3E, LCE1B, LCE2B, SPRR2E, SPRR2G, LCE2A, RPTN and CDSN were identified from the PPI network. The miRNA (hsa-miR-98-5p) was regarded as the mostly possible miRNA involved in OLP.


Sign in / Sign up

Export Citation Format

Share Document