Identification of potential hub genes and drugs in septic liver injury: A bioinformatic analysis
Yan Yang, Jing Lv, Jianfeng Chu, Guobin Song, Shujun Sun, Rui ChenBackground:
The liver is pivotal in the metabolic and innate immune responses of sepsis, managing bacteremia, cytokine regulation, and acute-phase protein synthesis. However, the liver’s susceptibility to damage during sepsis underscores the need to understand the mechanisms behind septic liver injury. Our objective was to apply bioinformatics to identify key genes and pathways involved in septic liver injury and to reveal potential therapeutic targets.
Methods:
We utilized pubmed2ensembl to identify genes associated with septic liver injury and performed functional annotation and pathway analysis using Xiantao. Protein-protein interactions were analyzed via the STRING database, and hub genes were identified with Cytoscape software. Candidate genes were validated with Metascape, and drug-gene interactions were explored using DGIDB.
Results:
Our analysis identified 63 genes implicated in sepsis-associated liver injury, refining our understanding of its molecular landscape. Gene ontology and Kyoto encyclopedia of genes and genomes analyses shortlisted 42 candidate genes, highlighting their roles in septic liver injury pathogenesis. An PPI network analysis extracted 18 genes, with MCODE-assisted analysis revealing a module of 8 key genes central to septic liver injury pathophysiology. These genes – TLR4, CXCL8, IL-18, IL-6, IL1B, tumor necrosis factor, NFKB1, and colony-stimulating factor 3 – are linked to 3 major signaling pathways: malaria, legionellosis, and the cellular response to lipopolysaccharide. Furthermore, 23 drugs targeting these genes were identified, suggesting their potential as therapeutic agents for septic liver injury.
Conclusion:
The genes TLR4, CXCL8, IL-18, IL-6, IL1B, tumor necrosis factor, NFKB1, and colony-stimulating factor 3 are central to the pathology of septic liver injury, acting as critical mediators of associated inflammatory processes. The correspondence of these genes with 23 drugs demonstrates their therapeutic potential, elucidating molecular targets for future interventions and paving the way for novel treatment strategies. This study provides a robust framework for subsequent research endeavors and the development of targeted therapies, enhancing our capacity to address septic liver injury effectively.