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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Published in | Frontiers in genetics Vol. 14; p. 1132361 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
23.02.2023
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Zhengzheng Yan, Southern Medical University, China Edited by: Yuan Liu, Shanghai Jiao Tong University, China Mengmeng Zhai, Alliance Pharma, United States These authors have contributed equally to this work and share first authorship Reviewed by: Hanghui Ye, University of Texas MD Anderson Cancer Center, United States This article was submitted to RNA, a section of the journal Frontiers in Genetics |
ISSN: | 1664-8021 1664-8021 |
DOI: | 10.3389/fgene.2023.1132361 |