Analysis of novel plasma protein biomarkers in sepsis using DIA mass spectrometry.

PURPOSE: This study used DIA mass spectrometry to identify novel plasma protein biomarkers for sepsis, aiming to find new diagnostic targets.

METHODS

A sepsis model in C57BL/6 mice, divided into Control and LPS groups, assessed survival post-LPS. Plasma samples measured inflammatory (IL-1β, IL-6, TNF-α) and thrombi (sTM, D2D) markers via ELISA. Organ changes in lungs, liver, kidneys, heart, and spleen were evaluated via HE staining. DIA proteomics identified proteins, and ROC curve validation assessed the predictive value of combined protein detection for sepsis diagnosis.

RESULTS

Survival rates showed about 50 % mortality in the LPS group 8-10 h post-administration, with all mice dying within 14 h. ELISA results showed higher levels of inflammatory and thrombotic markers in the LPS group. HE staining revealed organ damage and morphological changes in the LPS group. DIA quantitative proteomics identified 194 differentially expressed proteins (172 upregulated, 22 downregulated). GO terms included chemokine-mediated signaling and cellular response to interleukin-1. KEGG pathways showed enrichment in endocytosis and cytokine interactions. PPI network analysis and hub gene screening revealed key hub genes: IFNG, IL-6, IL-1β, and TIMP1. The ROC curves shows that compared to monitoring a single plasma protein indicator, the combined detection of these proteins are highly predictive for diagnosing sepsis.

CONCLUSION

IFNG, IL-6, IL-1β and TIMP1 hold potential as novel plasma biomarkers for the combined detection in sepsis patients. This study provides new insights into the diagnosis of plasma biomarkers for sepsis, although further research is needed to assess their functional significance and clinical applications.