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Identification and Verification of Potential Core Genes in Pediatric Septic Shock
Zhihao Xu1,2, Meiling Jiang3, Xiwen Bai1,2
1The Institute of Translational Medicine, The National Engineering Research Center for Bioengineering Drugs and the Technologies, Nanchang University, Nanchang, Jiangxi 330031, China.
Insights
This study identified novel hub genes, including GPR97 and TRAT1, as potential biomarkers and therapeutic targets for pediatric septic shock. These findings enhance understanding of septic shock
Area of Science:
- Genomics
- Molecular Biology
- Immunology
Background:
- Septic shock is a critical condition in pediatric intensive care units (PICU), characterized by high mortality and significant morbidity.
- Identifying reliable biomarkers and therapeutic targets is crucial for improving patient outcomes.
Purpose of the Study:
- To screen candidate biomarkers and potential therapeutic targets for pediatric septic shock.
- To investigate the molecular mechanisms underlying septic shock progression.
Main Methods:
- Utilized the GSE26440 dataset from Gene Expression Omnibus (GEO) comprising RNA samples from pediatric septic shock patients and normal controls.
- Performed Gene Ontology (GO) and KEGG pathway enrichment analyses to identify differentially expressed genes (DEGs).
- Constructed protein-protein interaction (PPI) networks using STRING and identified hub genes with Cytoscape's cytoHubba plugin.
Main Results:
- Identified 140 DEGs (98 up-regulated, 42 down-regulated) enriched in immune response and leukocyte activation pathways.
- Discovered key hub genes including MMP9, CEACAM8, ARG1, MCEMP1, LCN2, RETN, S100A12, GPR97, and TRAT1.
- Validated altered expression of several hub genes (MMP9, CEACAM8, ARG1, MCEMP1, LCN2, RETN, S100A12, GPR97) in human and mouse models, noting species-specific expression for TRAT1.
Conclusions:
- The study identified novel hub genes, particularly GPR97 and TRAT1, advancing the understanding of septic shock's molecular mechanisms.
- These identified genes hold promise as diagnostic biomarkers or therapeutic targets for septic shock management.
Background:
Septic shock is a frequent and costly problem among patients in the pediatric intensive care unit (PICU) and is associated with high mortality and devastating survivor morbidity. In this study, we aimed to screen candidate biomarkers and potential therapeutic targets for septic shock.
Methods:
GSE26440 dataset was downloaded from Gene Expression Omnibus (GEO), including 32 normal controls and 98 children with septic shock RNA samples from whole blood. The pathways and functional annotations of differentially expressed genes (DEGs) in the two types of samples were examined by GO and KEGG pathway enrichment analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool. Protein-protein interactions (PPI) of the above-described DEGs were investigated using the Search Tool for the Retrieval of Interacting Genes (STRING) and Hub gene identification was performed by the plug-in cytoHubba in Cytoscape software.
Results:
A total of 140 genes were identified as DEGs, of which 98 genes were up-regulated and 42 genes were down-regulated. GO function analysis showed that DEGs were significantly enriched in biological processes, including immune response, leukocyte activation involved in immune response, and so on. The top hub genes, namely MMP9, CEACAM8, ARG1, MCEMP1, LCN2, RETN, S100A12, GPR97, and TRAT1 were recognized from the protein-protein interaction (PPI) network. Furthermore, qRT-PCR results demonstrated that the mRNA level of MMP9, CEACAM8, ARG1, MCEMP1, LCN2, RETN, and S100A12 was elevated while GPR97 was decreased in involved mouse and human models. However, TRAT1 expression is species-dependent which was decreased in the mouse septic shock model but elevated in the human LPS-treated macrophages model.
Conclusion:
Taken together, the identification and validation of several novel hub genes, especially GPR97 and TRAT1, deepen our comprehension of the molecular mechanisms of septic shock progression. These genes may be therapeutic molecular targets or diagnostic biomarkers in patients with septic shock.
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