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

IF 4 3区 医学 Q1 INFECTIOUS DISEASES
Marta Martín-Fernández , Belén Sánchez-Quirós , Adrián García-Concejo , Álvaro Tamayo-Velasco , Rocío López-Herrero , Miguel Bardají , María Heredia-Rodríguez , Rocío Aller , Laura Sánchez de Prada , Hugo Gonzalo-Benito , Paula Moreno-Portales , Óscar Gorgojo-Galindo , Alba Montero-Jodra , Pedro Martínez-Paz , Rosario Calaveras , Rosa Prieto-Utrera , Rodrigo Poves-Álvarez , María Sherezade Tovar-Doncel , Salvador Resino , Amanda Fernández-Rodríguez , Esther Gómez-Sánchez
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引用次数: 0

Abstract

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.
循环细胞外囊泡miR-150-5p作为优化败血症和感染性休克临床管理的生物标志物:一项发现和验证研究
背景败血症和感染性休克仍然是外科患者死亡的主要原因。细胞外囊泡(ev)的作用,特别是它们的microRNAs (miRNAs)含量,已经成为检测和理解这些疾病的关键因素。因此,本研究旨在分析脓毒症和脓毒性休克患者循环血浆来源的ev - mirna,以确定有助于这些患者管理的差异生物标志物。方法对100例患者进行多中心前瞻性随访,其中感染性休克58例,脓毒症42例。分离ev - mirna并对其进行大量测序,以鉴定组间差异表达的mirna。采用受试者工作曲线(ROC)评价预测效果。结果在另一个验证队列中得到验证。此外,我们将我们的数据与血浆miRNA数据的外部队列进行了比较。结果两组患者共鉴定出18个SDE(统计学差异表达)ev - mirna。6种ev - mirna对感染性休克的检测能力较好。低水平的hsa-miR-150-5p检测脓毒性休克的能力最好(AUC: 0.852; 95 % CI: 0.75-0.96; p <; 0.001),敏感性为86.96 %,特异性为78.72 %。通过qPCR验证hsa-miR-150-5p与脓毒性休克的相关性,并证实其存在于血浆中。结论hsa-miR-150-5p水平在脓毒症休克和脓毒症患者中表达有显著差异。该生物标志物可能有助于早期风险分层,并指导术后脓毒症管理的临床决策。此外,我们的研究结果表明其作为脓毒症治疗靶点的潜力,尽管其作为治疗靶点的用途需要进一步研究。
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来源期刊
Journal of Infection and Public Health
Journal of Infection and Public Health PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH -INFECTIOUS DISEASES
CiteScore
13.10
自引率
1.50%
发文量
203
审稿时长
96 days
期刊介绍: The Journal of Infection and Public Health, first official journal of the Saudi Arabian Ministry of National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences and the Saudi Association for Public Health, aims to be the foremost scientific, peer-reviewed journal encompassing infection prevention and control, microbiology, infectious diseases, public health and the application of healthcare epidemiology to the evaluation of health outcomes. The point of view of the journal is that infection and public health are closely intertwined and that advances in one area will have positive consequences on the other. The journal will be useful to all health professionals who are partners in the management of patients with communicable diseases, keeping them up to date. The journal is proud to have an international and diverse editorial board that will assist and facilitate the publication of articles that reflect a global view on infection control and public health, as well as emphasizing our focus on supporting the needs of public health practitioners. It is our aim to improve healthcare by reducing risk of infection and related adverse outcomes by critical review, selection, and dissemination of new and relevant information in the field of infection control, public health and infectious diseases in all healthcare settings and the community.
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