A Histone Deacetylase Activity Model for the Discovery and Validation of Sepsis Biomarkers.

INTRODUCTION

Histone deacetylases (HDACs) play critical roles in immune regulation and inflammatory responses in sepsis. This study identified HDAC-related genes and explored their potential roles in sepsis.

MATERIALS AND

METHODS

HDAC scores were computed by ssGSEA. WGCNA was applied to identify HDAC-related gene modules, followed by functional enrichment analysis. Machine learning methods were employed to screen diagnostic biomarkers. Immune infiltration analysis and molecular docking were performed to validate gene-immune correlations and potential drugs. An in-vitro sepsis model was established by using lipopolysaccharide to induce THP-1-derived macrophages. The gene expression and inflammatory factor levels were assessed using qPCR, Western blot, and ELISA methods. Finally, the effect of TRIM24 knockdown on cell apoptosis and inflammatory responses was analyzed.

RESULTS

Two HDAC-related genes (TOM1L2, TRIM24) were identified as potential diagnostic biomarkers for sepsis, showing significant correlation with immune cell infiltration. Molecular docking confirmed the binding capacity of Acetaminophen, 8-azaguanine, and Ochratoxin A with the two biomarkers. In-vitro sepsis model showed that TRIM24 knockdown markedly lowered the levels of pro-inflammatory cytokines and apoptosis.

DISCUSSION: The two biomarkers, along with the RiskScore model, could potentially contribute to the prognostic assessment of sepsis and the development of personalized treatment. However, further experimental validation is also needed to substantiate our findings and to translate them into practical clinical applications.

CONCLUSION

This study identified TOM1L2 and TRIM24 as key HDAC-related biomarkers for sepsis, providing novel insights for the early diagnosis and targeted treatments of sepsis.