Circulating Extracellular Vesicle miR-150–5p as a biomarker for optimizing clinical management of sepsis and septic shock: A discovery and validation Study

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BACKGROUND: Sepsis and septic shock remain major causes of mortality in surgical patients. The role of extracellular vesicles (EVs), particularly their microRNAs (miRNAs) content, has emerged as key players in the detection and understanding of these conditions. Thus, this study aimed to profile circulating plasma-derived EV-miRNAs in patients with sepsis and septic shock to identify differential biomarkers that can facilitate the management of these patients. METHODS: A multicentric study was conducted in 100 patients who were followed prospectively, 58 developed septic shock and 42 developed sepsis. EV-miRNAs were isolated and massively sequenced to identify differentially expressed miRNAs between groups. Predictive performance was evaluated using receiver operating curves (ROC). Results were validated in an additional validation cohort. Furthermore, we compared our data with an external cohort of plasma miRNA data. RESULTS: Eighteen SDE (Statistically Differentially Expressed) EV-miRNAs were identified between the two groups of patients. Six EV-miRNAs had a good ability to detect septic shock. Low levels of hsa-miR-150-5p showed the best ability to detect septic shock (AUC: 0.852; 95 % CI: 0.75-0.96; p < 0.001) with a sensitivity of 86.96 % and a specificity of 78.72 %. hsa-miR-150-5p association with septic shock was validated and confirmed its presence in plasma via qPCR. CONCLUSION: In conclusion, hsa-miR-150-5p levels exhibit a significant differential expression between septic shock and sepsis patients. This biomarker may help in early risk stratification and guide clinical decisions in post-surgical sepsis management. Moreover, our findings suggest its potential as a therapeutic target in sepsis, although its use as a therapeutic target requires further investigation.

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