High THBS1 expression is associated with poorer outcomes in patients with sepsisHigh THBS1 levels linked to poorer outcomes in sepsis patients

BackgroundSepsis remains a major cause of mortality worldwide, and biomarkers that integrate inflammatory dysregulation, immune-cell localization, and prognostic relevance remain limited. To identify a candidate molecule linked to myeloid immune responses in sepsis, we performed an integrated analysis of public bulk transcriptomic datasets, single-cell RNA sequencing data, a small exploratory clinical RNA-sequencing cohort, and compound screening analyses.ResultsDifferential expression analysis and meta-analysis across public datasets identified THBS1 as a consistently altered transcript in sepsis. In a small exploratory peripheral-blood transcriptomic cohort comprising 23 patients with sepsis and 10 healthy controls, THBS1 was selected for downstream analysis on the basis of its position in the public-data protein–protein interaction network and the subsequent THBS1-focused analyses. The reused clinical RNA-sequencing cohort was retained only as an exploratory description and was not used to claim independent validation. Single-cell analysis suggested that THBS1 expression was more prominent in subsets of myeloid-related cell populations. Survival analysis in an external dataset indicated that high THBS1 expression was associated with poorer outcomes, but this finding should be interpreted as exploratory because formal adjustment for disease severity was not possible. Candidate compounds associated with THBS1 were further prioritized by database mining and molecular docking.ConclusionsThis study provides transcriptomic and computational evidence suggesting that THBS1 may be associated with myeloid-related immune activity and adverse prognosis in sepsis. Because the clinical cohort was small, protein-level validation and functional experiments were not performed, and substantial heterogeneity was observed across public datasets, these findings should be interpreted as preliminary and hypothesis-generating.