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外泌体衍生的微小RNA在术后脓毒性休克和非脓毒性休克患者中的诊断作用研究

Study on the diagnostic role of exosome-derived miRNAs in postoperative septic shock and non-septic shock patients.

作者信息

García-Concejo Adrián, Sánchez-Quirós Belén, Gómez-Sánchez Esther, Sánchez-de Prada Laura, Tamayo-Velasco Álvaro, Tovar-Doncel María Sherezade, Lorenzo Mario, Gómez-Pesquera Estefanía, Poves-Álvarez Rodrigo, Bernardo David, Martín-Fernández Marta, Gonzalo-Benito Hugo, Moreno-Portales Paula, Prieto-Utrera Rosa, Bardají-Carrillo Miguel, López-Herrero Rocío, Fernández Arranz María, Calaveras-Fernández Rosario, Tomillo-Cebrián Fé, Aydillo Teresa, Jiménez-Sousa María Ángeles, Fernández-Rodríguez Amanda, Resino Salvador, Heredia-Rodríguez María, Martínez-Paz Pedro, Tamayo Eduardo

机构信息

Biomedical Research Networking Centre in Infectious Diseases (CIBERINFEC), Carlos III Health Institute, Madrid, Spain.

Group for Biomedical Research in Critical Care (Biocritic), Avenida Ramón y Cajal 7, 47005, Valladolid, Spain.

出版信息

Crit Care. 2025 Mar 3;29(1):96. doi: 10.1186/s13054-025-05320-y.

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.

摘要

背景

及时诊断感染性休克至关重要,但具有挑战性,尤其是因为它在临床上与非感染性休克相似。细胞外囊泡衍生的微小RNA(miRNA)可作为区分感染性休克与非感染性休克的生物标志物,为术后患者提供更准确的诊断工具。本研究旨在识别细胞外囊泡衍生的miRNA特征,以区分术后患者的感染性休克与非感染性休克, potentially improving diagnostic accuracy and clinical decision-making.

方法

对休克患者的miRNA谱进行了一项多中心前瞻性研究。从两家西班牙医院的重症监护病房招募了两个队列:一个有109名患者的发现队列和一个有52名患者的验证队列。在休克诊断后24小时内采集血浆样本,并进行miRNA测序。对发现队列的高通量测序数据进行分析,以识别差异表达的miRNA。这些发现通过qPCR在验证队列中进行验证。

结果

在感染性休克和非感染性休克患者之间,有30种miRNA被确定为差异显著表达。其中,六种miRNA——miR-100-5p、miR-484、miR-10a-5p、miR-148a-3p、miR-342-3p和miR-451a——对感染性休克具有强大的诊断能力。miR-100-5p、miR-148a-3p和miR-451a的组合曲线下面积为0.894,在验证队列中的qPCR验证得出曲线下面积为0.960。

结论

本研究强调细胞外囊泡衍生的miRNA作为区分感染性休克与非感染性休克的有前景的生物标志物。所识别的三种miRNA特征具有显著潜力增强感染性休克的诊断,从而有助于对术后患者进行及时和适当的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/11874436/b52815023d0b/13054_2025_5320_Fig1_HTML.jpg

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