Identifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysis
Abstract Background Intracranial aneurysm (IA) is the most common cerebrovascular disease, and subarachnoid hemorrhage caused by its rupture can seriously impede nerve function. Pyroptosis is an inflammatory mode of cell death whose underlying mechanisms involving the occurrence and rupture of IAs r...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Biological Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40659-023-00464-z |
| _version_ | 1797453802216882176 |
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| author | Donglin Zhou Yimin Zhu Peng Jiang Tongfu Zhang Jianfeng Zhuang Tao Li Linzeng Qi Yunyan Wang |
| author_facet | Donglin Zhou Yimin Zhu Peng Jiang Tongfu Zhang Jianfeng Zhuang Tao Li Linzeng Qi Yunyan Wang |
| author_sort | Donglin Zhou |
| collection | DOAJ |
| description | Abstract Background Intracranial aneurysm (IA) is the most common cerebrovascular disease, and subarachnoid hemorrhage caused by its rupture can seriously impede nerve function. Pyroptosis is an inflammatory mode of cell death whose underlying mechanisms involving the occurrence and rupture of IAs remain unclear. In this study, using bioinformatics analysis, we identified the potential pyroptosis-related genes (PRGs) and performed their inflammatory response mechanisms in IAs. Methods The mRNA expression matrix of the IA tissue was obtained from the Gene Expression Omnibus database, and 51 PRGs were obtained from previous articles collected from PubMed. The differentially expressed PRGs (DEPRGs) were performed using R software. Subsequently, we performed enrichment analysis, constructed a protein–protein interaction network, performed weighted gene coexpression network analysis (WGCNA) and external validation using another dataset, and identified a correlation between hub genes and immune cell infiltration. Finally, the expression and tissue distribution of these hub genes in IA tissues were detected using Western blotting and immunohistochemical (IHC) staining. Results In total, 12 DEPRGs associated with IA were identified in our analysis, which included 11 up-regulated and one down-regulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the DEPRGs were mostly enriched in the NOD-like receptor signaling pathway, interleukin-1 beta production, and the inflammasome complex. Three hub genes, NLRP3, IL1B and IL18, were identified using Cytoscape software and the WGCNA correlation module, and external validation revealed statistically significant differences between the expression of these hub genes in the ruptured and unruptured aneurysm groups (p < 0.05). Furthermore, all AUC values were > 0.75. Immune cell infiltration analysis suggested that the hub genes are related to CD8 T cell, macrophages and mast cells. Finally, IHC staining revealed that the protein levels of these hub genes were higher in ruptured and unruptured IA tissues than in normal tissues (p < 0.05). Conclusion The results of bioinformatics analysis showed that pyroptosis is closely related to the formation and rupture of IA, and identified three potential hub genes involved in the pyroptosis and infiltration ofcells. Our findings may improve the understanding of the mechanisms underlying pyroptosis in IA. |
| first_indexed | 2024-03-09T15:28:07Z |
| format | Article |
| id | doaj.art-42d8318724c84879871339049aa28e53 |
| institution | Directory Open Access Journal |
| issn | 0717-6287 |
| language | English |
| last_indexed | 2024-03-09T15:28:07Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Biological Research |
| spelling | doaj.art-42d8318724c84879871339049aa28e532023-11-26T12:23:52ZengBMCBiological Research0717-62872023-09-0156111810.1186/s40659-023-00464-zIdentifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysisDonglin Zhou0Yimin Zhu1Peng Jiang2Tongfu Zhang3Jianfeng Zhuang4Tao Li5Linzeng Qi6Yunyan Wang7Department of Neurosurgery, Qilu Hospital of Shandong University, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Orthopedics, Qilu Hospital of Shandong UniversityJiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical UniversityDepartment of Neurosurgery, Qilu Hospital of Shandong University, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital of Shandong University, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, The Third Affiliated Hospital of Shandong First Medical UniversityDepartment of Orthopedics, Qilu Hospital of Shandong UniversityDepartment of Neurosurgery, Qilu Hospital of Shandong University, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityAbstract Background Intracranial aneurysm (IA) is the most common cerebrovascular disease, and subarachnoid hemorrhage caused by its rupture can seriously impede nerve function. Pyroptosis is an inflammatory mode of cell death whose underlying mechanisms involving the occurrence and rupture of IAs remain unclear. In this study, using bioinformatics analysis, we identified the potential pyroptosis-related genes (PRGs) and performed their inflammatory response mechanisms in IAs. Methods The mRNA expression matrix of the IA tissue was obtained from the Gene Expression Omnibus database, and 51 PRGs were obtained from previous articles collected from PubMed. The differentially expressed PRGs (DEPRGs) were performed using R software. Subsequently, we performed enrichment analysis, constructed a protein–protein interaction network, performed weighted gene coexpression network analysis (WGCNA) and external validation using another dataset, and identified a correlation between hub genes and immune cell infiltration. Finally, the expression and tissue distribution of these hub genes in IA tissues were detected using Western blotting and immunohistochemical (IHC) staining. Results In total, 12 DEPRGs associated with IA were identified in our analysis, which included 11 up-regulated and one down-regulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the DEPRGs were mostly enriched in the NOD-like receptor signaling pathway, interleukin-1 beta production, and the inflammasome complex. Three hub genes, NLRP3, IL1B and IL18, were identified using Cytoscape software and the WGCNA correlation module, and external validation revealed statistically significant differences between the expression of these hub genes in the ruptured and unruptured aneurysm groups (p < 0.05). Furthermore, all AUC values were > 0.75. Immune cell infiltration analysis suggested that the hub genes are related to CD8 T cell, macrophages and mast cells. Finally, IHC staining revealed that the protein levels of these hub genes were higher in ruptured and unruptured IA tissues than in normal tissues (p < 0.05). Conclusion The results of bioinformatics analysis showed that pyroptosis is closely related to the formation and rupture of IA, and identified three potential hub genes involved in the pyroptosis and infiltration ofcells. Our findings may improve the understanding of the mechanisms underlying pyroptosis in IA.https://doi.org/10.1186/s40659-023-00464-zIntracranial aneurysmPyroptosisInflammatory cell deathGene expression omnibusBioinformatics analysis |
| spellingShingle | Donglin Zhou Yimin Zhu Peng Jiang Tongfu Zhang Jianfeng Zhuang Tao Li Linzeng Qi Yunyan Wang Identifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysis Biological Research Intracranial aneurysm Pyroptosis Inflammatory cell death Gene expression omnibus Bioinformatics analysis |
| title | Identifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysis |
| title_full | Identifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysis |
| title_fullStr | Identifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysis |
| title_full_unstemmed | Identifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysis |
| title_short | Identifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysis |
| title_sort | identifying pyroptosis and inflammation related genes in intracranial aneurysms based on bioinformatics analysis |
| topic | Intracranial aneurysm Pyroptosis Inflammatory cell death Gene expression omnibus Bioinformatics analysis |
| url | https://doi.org/10.1186/s40659-023-00464-z |
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