Construction of a robust sepsis prognostic classifier based on E3 ubiquitin ligase-related genes

Sepsis is a life-threatening disease with high mortality and one of the leading causes of death worldwide. Although studies have shown that ubiquitylation is closely related to the occurrence and development of sepsis, the prognostic and diagnostic value of ubiquitylation-related genes in sepsis remains unclear. In this study, we obtained sepsis datasets from the Gene Expression Omnibus (GEO) database and identified ubiquitylation-related genes from the Ubiquitin and Ubiquitin-like Conjugation Database (iUUCD). We identified 159 differentially expressed genes related to ubiquitylation between sepsis patients and healthy individuals, and the prognosis of sepsis subgroups distinguished by these ubiquitylation genes showed significant differences, demonstrating the importance of the ubiquitylation phenotype in sepsis. To explore the prognostic value of ubiquitination-related genes in sepsis, we constructed a ubiquitylation-related score (URS) through LASSO analysis, random forest, and Cox regression analysis. Importantly, we validated the reliability of this model in both the GEO database cohort and the external cohort data from our unit. Finally, we identified LTB and TCP11L2 as key ubiquitylation-related genes, explored their expression patterns and potential biological context through single-cell RNA sequence analysis, and validated their expression and diagnostic value using patient blood samples. Our study suggests a link between ubiquitylation and sepsis, which can be used as a potential biomarker to guide the diagnosis, treatment, and prognosis of sepsis and proposes new ideas for future clinical research.