Abstract
Background: microRNAs (miRNAs) from circulating extracellular vesicles (EVs) have been reported as disease biomarkers. This study aimed to identify the diagnostic value of plasma EV-miRNAs in sepsis. Methods: EVs were separated from the plasma of sepsis patients at admission and healthy controls. The expression of EV-miRNAs was evaluated by microarray and qRT-PCR. Results: A preliminary miRNA microarray of plasma EVs from a discovery cohort of 3 sepsis patients at admission and three healthy controls identified 11 miRNAs with over 2-fold upregulation in sepsis group. Based on this finding, EV samples from a validation cohort of 37 sepsis patients at admission and 25 healthy controls were evaluated for the expression of the 6 miRNAs relating injury and inflammation via qRT-PCR. Elevated expression of miR-483-3p and let-7d-3p was validated in sepsis patients and corroborated in a mouse model of sepsis. miR-483-3p and let-7d-3p levels positively correlated with the disease severity. Additionally, a combination of miR-483-3p and let-7d-3p had diagnostic value for sepsis. Furthermore, bioinformatic analysis and experimental validation showed that miR-483-3p and let-7d-3p target pathways regulating immune response and endothelial function. Conclusion: The present study reveals the potential role of plasma EV-miRNAs in the pathogenesis of sepsis and the utility of combining miR-483-3p and let-7d-3p as biomarkers for early sepsis diagnosis.
Highlights
Sepsis, which is defined as life-threatening organ dysfunction as the result of dysregulation of host response to an infection, is the primary cause of hospital death in the intensive care units (ICU)
Thirty-seven patients with sepsis and 25 healthy controls were enrolled in the validation cohort
A combined Receiver operating characteristic (ROC) curve with miR-483-3p and let-7d-3p provided additional benefit to the diagnostic performance (AUC = 0.791, 95% CI 0.668–0.914, p = 0.001)
Summary
Sepsis, which is defined as life-threatening organ dysfunction as the result of dysregulation of host response to an infection, is the primary cause of hospital death in the intensive care units (ICU). The cytokine storm and secondary immunosuppression often culminate in multiple organ failure, the EV miRNA for Sepsis Diagnosis leading cause of mortality (Delano and Ward, 2016). Diagnosis and management of sepsis are essential to reduce organ failure and death through prompt antibiotics, pressors, and adjuvant treatment (Marik and Farkas, 2018). Circulating miRNAs from serum or plasma have been examined as diagnostic and prognostic biomarkers for sepsis (Giza et al, 2016). Serum miR-150 was shown as a predictor for survival for patients with critical illness and sepsis (Roderburg et al, 2013). Elevated levels of serum miR-133a were an independent predictor for mortality in sepsis patients (Tacke et al, 2014). This study aimed to identify the diagnostic value of plasma EV-miRNAs in sepsis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
