SomaScan P11K Proteomics Characterizes the Plasma Proteomic Profile of Exertional Heat Stroke and Highlights Innate Immune-Related Signaling Molecules

Exertional heat stroke (EHS) is a life-threatening heat-related illness associated with systemic inflammation and multiple organ injury, yet its circulating immune-related molecular features remain incompletely characterized. We used the SomaScan P11K platform to compare plasma protein profiles between patients with EHS and healthy controls and identified 120 differentially expressed proteins, including 71 upregulated and 49 downregulated proteins. Functional annotation, GO and KEGG enrichment analyses, ssGSEA, GSEA, protein-protein interaction network analysis, CytoHubba, and MCODE were used to characterize biological pathways and prioritize candidate proteins. Enrichment analyses highlighted innate immunity- and inflammation-related pathways, and network analyses prioritized TLR2, TLR7, CXCL10, ISG15, and IFIT3. In an independent sample set, ELISA showed significantly increased plasma TLR2 levels in patients with EHS, consistent with the proteomic findings. DSigDB analysis further identified candidate compound-associated signals, including Chlorophyllin, Prenylamine, and Inosinic acid. These findings provide an exploratory plasma proteomic resource for EHS and prioritize innate immune-related molecular features, particularly TLR2, for further validation and mechanistic investigation.