Differential expression of pyroptosis-related genes in the hippocampus of patients with Alzheimer’s disease
Abstract Background Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder with insidious onset. Some scholars believe that there is a close relationship between pyroptosis and AD. However, studies with evidence supporting this relationship are lacking. Materials and methods The micro...
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | BMC Medical Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12920-023-01479-x |
| _version_ | 1797863277109182464 |
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| author | Pengcheng Xia Huijun Ma Jing Chen Yingchao Liu Xiaolin Cui Cuicui Wang Shuai Zong Le Wang Yun Liu Zhiming Lu |
| author_facet | Pengcheng Xia Huijun Ma Jing Chen Yingchao Liu Xiaolin Cui Cuicui Wang Shuai Zong Le Wang Yun Liu Zhiming Lu |
| author_sort | Pengcheng Xia |
| collection | DOAJ |
| description | Abstract Background Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder with insidious onset. Some scholars believe that there is a close relationship between pyroptosis and AD. However, studies with evidence supporting this relationship are lacking. Materials and methods The microarray data of AD were retrieved from the Gene Expression Omnibus (GEO) database with the datasets merged using the R package inSilicoMerging. R software package Limma was used to perform the differential expression analysis to identify the differentially expressed genes (DEGs). We further performed the enrichment analyses of the DEGs based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases to identify the metabolic pathways with a significant difference. The Gene Set Enrichment Analysis (GSEA) was applied to identify the significant pathways. The protein-protein interaction (PPI) network was constructed based on the STRING database with the hub genes identified. Quantitative real-time PCR (qRT-PCR) analyses based on HT22 cells were performed to validate the findings based on the microarray analysis. Gene expression correlation heatmaps were generated to evaluate the relationships among the genes. Results A new dataset was derived by merging 4 microarray datasets in the hippocampus of AD patients in the GEO database. Differential gene expression analysis yielded a volcano plot of a total of 20 DEGs (14 up-regulated and 6 down-regulated). GO analysis revealed a group of GO terms with a significant difference, e.g., cytoplasmic vesicle membrane, vesicle membrane, and monocyte chemotaxis. KEGG analysis detected the metabolic pathways with a significant difference, e.g., Rheumatoid arthritis and Fluid shear stress and atherosclerosis. The results of the Gene Set Enrichment Analysis of the microarray data showed that gene set ALZHEIMER_DISEASE and the gene set PYROPTOSIS were both up-regulated. PPI network showed that pyroptosis-related genes were divided into two groups. In the Aβ-induced HT22 cell model, three genes (i.e., BAX, IL18, and CYCS) were revealed with significant differences. Gene expression correlation heatmaps revealed strong correlations between pyroptotic genes and AD-related genes. Conclusion The pyroptosis-related genes BAX, IL18, and CYCS were significantly different between AD patients and normal controls. |
| first_indexed | 2024-04-09T22:34:00Z |
| format | Article |
| id | doaj.art-878d34a479674c498013a9477ceedb8a |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-04-09T22:34:00Z |
| publishDate | 2023-03-01 |
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| series | BMC Medical Genomics |
| spelling | doaj.art-878d34a479674c498013a9477ceedb8a2023-03-22T12:37:47ZengBMCBMC Medical Genomics1755-87942023-03-0116111310.1186/s12920-023-01479-xDifferential expression of pyroptosis-related genes in the hippocampus of patients with Alzheimer’s diseasePengcheng Xia0Huijun Ma1Jing Chen2Yingchao Liu3Xiaolin Cui4Cuicui Wang5Shuai Zong6Le Wang7Yun Liu8Zhiming Lu9Department of Clinical Laboratory Medicine, Shandong Provincial Hospital, Shandong First Medical UniversityClinical Laboratory, Qingdao Women and Children’s HospitalDiscipline of Anatomy and Pathology, Shandong First Medical UniversityDepartment of Clinical Laboratory Medicine, Shandong Provincial Hospital, Shandong First Medical UniversitySchool of Medicine, Shandong UniversityDepartment of Clinical Laboratory Medicine, Shandong Provincial Hospital, Shandong First Medical UniversityDepartment of Clinical Laboratory Medicine, Shandong Provincial Hospital, Shandong First Medical UniversityDepartment of Clinical Laboratory Medicine, Shandong Provincial Hospital, Shandong First Medical UniversityDepartment of Clinical Laboratory Medicine, Shandong Provincial Hospital, Shandong First Medical UniversityDepartment of Clinical Laboratory Medicine, Shandong Provincial Hospital, Shandong First Medical UniversityAbstract Background Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder with insidious onset. Some scholars believe that there is a close relationship between pyroptosis and AD. However, studies with evidence supporting this relationship are lacking. Materials and methods The microarray data of AD were retrieved from the Gene Expression Omnibus (GEO) database with the datasets merged using the R package inSilicoMerging. R software package Limma was used to perform the differential expression analysis to identify the differentially expressed genes (DEGs). We further performed the enrichment analyses of the DEGs based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases to identify the metabolic pathways with a significant difference. The Gene Set Enrichment Analysis (GSEA) was applied to identify the significant pathways. The protein-protein interaction (PPI) network was constructed based on the STRING database with the hub genes identified. Quantitative real-time PCR (qRT-PCR) analyses based on HT22 cells were performed to validate the findings based on the microarray analysis. Gene expression correlation heatmaps were generated to evaluate the relationships among the genes. Results A new dataset was derived by merging 4 microarray datasets in the hippocampus of AD patients in the GEO database. Differential gene expression analysis yielded a volcano plot of a total of 20 DEGs (14 up-regulated and 6 down-regulated). GO analysis revealed a group of GO terms with a significant difference, e.g., cytoplasmic vesicle membrane, vesicle membrane, and monocyte chemotaxis. KEGG analysis detected the metabolic pathways with a significant difference, e.g., Rheumatoid arthritis and Fluid shear stress and atherosclerosis. The results of the Gene Set Enrichment Analysis of the microarray data showed that gene set ALZHEIMER_DISEASE and the gene set PYROPTOSIS were both up-regulated. PPI network showed that pyroptosis-related genes were divided into two groups. In the Aβ-induced HT22 cell model, three genes (i.e., BAX, IL18, and CYCS) were revealed with significant differences. Gene expression correlation heatmaps revealed strong correlations between pyroptotic genes and AD-related genes. Conclusion The pyroptosis-related genes BAX, IL18, and CYCS were significantly different between AD patients and normal controls.https://doi.org/10.1186/s12920-023-01479-xAlzheimer's diseasePyroptosisHippocampusFunctional enrichment analysisProtein-protein interaction network |
| spellingShingle | Pengcheng Xia Huijun Ma Jing Chen Yingchao Liu Xiaolin Cui Cuicui Wang Shuai Zong Le Wang Yun Liu Zhiming Lu Differential expression of pyroptosis-related genes in the hippocampus of patients with Alzheimer’s disease BMC Medical Genomics Alzheimer's disease Pyroptosis Hippocampus Functional enrichment analysis Protein-protein interaction network |
| title | Differential expression of pyroptosis-related genes in the hippocampus of patients with Alzheimer’s disease |
| title_full | Differential expression of pyroptosis-related genes in the hippocampus of patients with Alzheimer’s disease |
| title_fullStr | Differential expression of pyroptosis-related genes in the hippocampus of patients with Alzheimer’s disease |
| title_full_unstemmed | Differential expression of pyroptosis-related genes in the hippocampus of patients with Alzheimer’s disease |
| title_short | Differential expression of pyroptosis-related genes in the hippocampus of patients with Alzheimer’s disease |
| title_sort | differential expression of pyroptosis related genes in the hippocampus of patients with alzheimer s disease |
| topic | Alzheimer's disease Pyroptosis Hippocampus Functional enrichment analysis Protein-protein interaction network |
| url | https://doi.org/10.1186/s12920-023-01479-x |
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