Co-expression and interaction network analysis reveals dysregulated neutrophil and T-cell activation as the core mechanism associated with septic shock
Septic shock as a subset of sepsis, has a much higher mortality, while the mechanism is still elusive. This study was aimed at identifying core mechanisms associated with septic shock and its high mortality by investigating transcriptome data. We screened 72 septic-shock-associated genes (SSAGs) wit...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1132361/full |
| _version_ | 1797897143354130432 |
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| author | Shaobo Zhao Kun Zhu Xiaoyi Li Xiaohui Zhong Yanan Zhao Zhenkai Le Zhicong Liu Yi Xiao Dengming Lai Dengming Lai Na Jiao Qiang Shu |
| author_facet | Shaobo Zhao Kun Zhu Xiaoyi Li Xiaohui Zhong Yanan Zhao Zhenkai Le Zhicong Liu Yi Xiao Dengming Lai Dengming Lai Na Jiao Qiang Shu |
| author_sort | Shaobo Zhao |
| collection | DOAJ |
| description | Septic shock as a subset of sepsis, has a much higher mortality, while the mechanism is still elusive. This study was aimed at identifying core mechanisms associated with septic shock and its high mortality by investigating transcriptome data. We screened 72 septic-shock-associated genes (SSAGs) with differential expression between septic shock and sepsis in the discovery dataset. Further gene set enrichment analysis identified upregulated neutrophil activation and impaired T-cell activation in septic shock. Co-expression analysis revealed nine co-expressed gene modules. In addition, we determined twenty-one prognostic SSAGs using cox regression analysis in an independent dataset. Moreover, protein–protein interaction (PPI) network revealed two clusters. Among these neutrophil activation was enriched in the most positively-related modules and the cluster2 PPI network, while T-cell activation was enriched in both the most negatively-related module and one of the most positively-related modules as well as the cluster1 PPI network. ELANE, LCN2 and IFI44 were identified as hub genes with CytoHubba methods and semantic similarity analysis. Notably, ELANE was the only prognostic gene and was further validated in an external dataset. Blood neutrophil count was demonstrated to increase in septic shock and be a risky factor of prognosis based on clinical data. In conclusions, septic shock is associated with upregulated neutrophil activation and dysregulated T-cell activation. Three hub genes might have potentials as sensitive markers for the further translational research and ELANE could be a robust prognostic biomarker and effective therapeutic target. |
| first_indexed | 2024-04-10T07:54:03Z |
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| id | doaj.art-428f22c87cc84ad8bdadbeff2c4a942d |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-10T07:54:03Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-428f22c87cc84ad8bdadbeff2c4a942d2023-02-23T06:48:48ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-02-011410.3389/fgene.2023.11323611132361Co-expression and interaction network analysis reveals dysregulated neutrophil and T-cell activation as the core mechanism associated with septic shockShaobo Zhao0Kun Zhu1Xiaoyi Li2Xiaohui Zhong3Yanan Zhao4Zhenkai Le5Zhicong Liu6Yi Xiao7Dengming Lai8Dengming Lai9Na Jiao10Qiang Shu11Department of Pediatric Surgery, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Pathology, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaNational Clinical Research Center for Child Health, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Pediatric Surgery, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Pediatric Surgery, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Pediatric Surgery, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Pediatric Surgery, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaNational Clinical Research Center for Child Health, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Pediatric Surgery, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaNational Clinical Research Center for Child Health, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaNational Clinical Research Center for Child Health, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Pediatric Surgery, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaSeptic shock as a subset of sepsis, has a much higher mortality, while the mechanism is still elusive. This study was aimed at identifying core mechanisms associated with septic shock and its high mortality by investigating transcriptome data. We screened 72 septic-shock-associated genes (SSAGs) with differential expression between septic shock and sepsis in the discovery dataset. Further gene set enrichment analysis identified upregulated neutrophil activation and impaired T-cell activation in septic shock. Co-expression analysis revealed nine co-expressed gene modules. In addition, we determined twenty-one prognostic SSAGs using cox regression analysis in an independent dataset. Moreover, protein–protein interaction (PPI) network revealed two clusters. Among these neutrophil activation was enriched in the most positively-related modules and the cluster2 PPI network, while T-cell activation was enriched in both the most negatively-related module and one of the most positively-related modules as well as the cluster1 PPI network. ELANE, LCN2 and IFI44 were identified as hub genes with CytoHubba methods and semantic similarity analysis. Notably, ELANE was the only prognostic gene and was further validated in an external dataset. Blood neutrophil count was demonstrated to increase in septic shock and be a risky factor of prognosis based on clinical data. In conclusions, septic shock is associated with upregulated neutrophil activation and dysregulated T-cell activation. Three hub genes might have potentials as sensitive markers for the further translational research and ELANE could be a robust prognostic biomarker and effective therapeutic target.https://www.frontiersin.org/articles/10.3389/fgene.2023.1132361/fullbioinformaticsneutrophilELANET cellseptic shock |
| spellingShingle | Shaobo Zhao Kun Zhu Xiaoyi Li Xiaohui Zhong Yanan Zhao Zhenkai Le Zhicong Liu Yi Xiao Dengming Lai Dengming Lai Na Jiao Qiang Shu Co-expression and interaction network analysis reveals dysregulated neutrophil and T-cell activation as the core mechanism associated with septic shock Frontiers in Genetics bioinformatics neutrophil ELANE T cell septic shock |
| title | Co-expression and interaction network analysis reveals dysregulated neutrophil and T-cell activation as the core mechanism associated with septic shock |
| title_full | Co-expression and interaction network analysis reveals dysregulated neutrophil and T-cell activation as the core mechanism associated with septic shock |
| title_fullStr | Co-expression and interaction network analysis reveals dysregulated neutrophil and T-cell activation as the core mechanism associated with septic shock |
| title_full_unstemmed | Co-expression and interaction network analysis reveals dysregulated neutrophil and T-cell activation as the core mechanism associated with septic shock |
| title_short | Co-expression and interaction network analysis reveals dysregulated neutrophil and T-cell activation as the core mechanism associated with septic shock |
| title_sort | co expression and interaction network analysis reveals dysregulated neutrophil and t cell activation as the core mechanism associated with septic shock |
| topic | bioinformatics neutrophil ELANE T cell septic shock |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1132361/full |
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