Abstract
BACKGROUND: Diagnosing septic shock promptly is essential but challenging, especially due to its clinical similarity to non-septic shock. Extracellular vesicle-derived miRNAs may serve as biomarkers to distinguish septic shock from non-septic shock, providing a more accurate diagnostic tool for postsurgical patients. This study aims to identify extracellular vesicle-derived miRNA signatures that differentiate septic shock from non-septic shock in postsurgical patients, potentially improving diagnostic accuracy and clinical decision-making. METHODS: A multicentre, prospective study was conducted on miRNA profiles in shock patients. Two cohorts were recruited from the Intensive Care Units of two Spanish hospitals: a discovery cohort with 109 patients and a validation cohort with 52 patients. Plasma samples were collected within 24 h of shock diagnosis and subjected to miRNA sequencing. High-throughput sequencing data from the discovery cohort were analysed to identify differentially expressed miRNAs. These findings were validated via qPCR in the validation cohort. RESULTS: Thirty miRNAs were identified as significantly differentially expressed between septic and non-septic shock patients. Among these, six miRNAs-miR-100-5p, miR-484, miR-10a-5p, miR-148a-3p, miR-342-3p, and miR-451a-demonstrated strong diagnostic capabilities for septic shock. A combination of miR-100-5p, miR-148a-3p, and miR-451a achieved an area under the curve of 0.894, with qPCR validation in the validation cohort yielding an area under the curve of 0.960. CONCLUSIONS: This study highlights extracellular vesicle-derived miRNAs as promising biomarkers for differentiating septic from non-septic shock. The identified three-miRNA signature has significant potential to enhance septic shock diagnosis, thereby aiding in timely and appropriate treatment for postsurgical patients.