Schiavello Martina, Bosco Ornella, Vizio Barbara, Sciarrillo Alberto, Pensa Anna, Pivetta Emanuele, Morello Fulvio, Risso Daniela, Montrucchio Giuseppe, Mariano Filippo, Lupia Enrico
Department of Medical Science, University of Turin, 10126 Turin, Italy.
Plastic Surgery and Burn Center, Department of General and Specialized Surgery, City of Health and Science, CTO Hospital, 10126 Turin, Italy.
Int J Mol Sci. 2025 Feb 21;26(5):1844. doi: 10.3390/ijms26051844.
Sepsis is the leading cause of mortality in patients with burn injuries and it may represent, in these patients, a real diagnostic challenge. Here we studied the profile of miRNAs contained in extracellular vesicles (EVs) (EV-miRNAs) isolated from plasma from burn patients complicated by sepsis at admission and 7 days later. We enrolled 28 burn patients, 18 with (Burn Septic Patients-BSPs) and 10 without (Burn non-Septic Patients-BnSPs) sepsis. Ten healthy subjects (HSs) were used as additional controls. After EV isolation by charge precipitation and miRNA extraction, we proceeded with a two-phase approach. Through a first screening phase, we identified 178 miRNAs differentially expressed in BSPs compared to HSs. Among these, by a validation phase based on qRT-PCR, we found that miR-483-5p, miR-193a-5p, and miR-188-3p were increased in the BSPs compared to the BnSPs and HSs. Upon ROC analysis, all three miRNAs showed a good accuracy in differentiating BSPs from BnSPs, especially miR-483-5p (AUC = 0.955, -value = 0.001). Moreover, we found 173 miRNAs differentially expressed in BSPs after 7 days from enrollment compared to T0, among whose miR-1-3p, miR-34a-3p, and miR-193a-5p decreased in BSPs after 7 days, in parallel with a decrease in SOFA scores. Finally, the other two miRNAs, miR-34a-3p and miR-193a-5p, positively correlated with the SOFA score. In conclusion, we identified several miRNAs-namely miR-483-5p, miR-193a-5p, and miR-188-3p-with potential clinical utility as diagnostic biomarkers in a heterogeneous population of burn patients at high risk of developing sepsis. Moreover, we found some miRNAs (miR-1-3p, miR-34a-3p, and miR-193a-5p) that vary according to the course of sepsis and others (miR-34a-3p and miR-193a-5p) that are associated with its clinical severity.
脓毒症是烧伤患者死亡的主要原因，在这些患者中，它可能是一个真正的诊断挑战。在这里，我们研究了从入院时并发脓毒症的烧伤患者以及7天后的血浆中分离出的细胞外囊泡（EVs）（EV-miRNAs）中所含miRNA的特征。我们招募了28名烧伤患者，其中18名患有脓毒症（烧伤脓毒症患者-BSPs），10名没有脓毒症（烧伤非脓毒症患者-BnSPs）。另外选取10名健康受试者（HSs）作为对照。通过电荷沉淀法分离EV并提取miRNA后，我们采用了两阶段方法。在第一阶段筛选中，我们鉴定出与HSs相比，BSPs中有178种miRNA差异表达。其中，通过基于qRT-PCR的验证阶段，我们发现与BnSPs和HSs相比，BSPs中miR-483-5p、miR-193a-5p和miR-188-3p有所增加。经ROC分析，所有这三种miRNA在区分BSPs和BnSPs方面都具有良好的准确性，尤其是miR-483-5p（AUC = 0.955，P值 = 0.001）。此外，我们发现与入院时（T0）相比，入组7天后BSPs中有173种miRNA差异表达，其中miR-1-3p、miR-34a-3p和miR-193a-5p在BSPs中7天后有所下降，同时序贯器官衰竭评估（SOFA）评分也下降。最后，另外两种miRNA，miR-34a-3p和miR-193a-5p与SOFA评分呈正相关。总之，我们鉴定出了几种miRNA，即miR-483-5p、miR-193a-5p和miR-188-3p，它们在有发生脓毒症高风险的异质性烧伤患者群体中具有作为诊断生物标志物的潜在临床应用价值。此外，我们还发现了一些根据脓毒症病程而变化的miRNA（miR-1-3p、miR-34a-3p和miR-193a-5p）以及其他与脓毒症临床严重程度相关的miRNA（miR-34a-3p和miR-193a-5p）。
