{"title":"MicroRNAs in sepsis diagnosis: A systematic review and meta-analysis toward evidence-based biomarker development.","authors":"Shu-Hui Chen, Sameer Noor, Wei-Hsuan Liu, Tzu-Ti Tien, Chin-Chieh Wu, Kuan-Fu Chen","doi":"10.1016/j.jmii.2026.06.004","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Sepsis diagnosis remains challenging, and conventional biomarkers such as CRP and PCT show limited specificity. Circulating microRNAs (miRNAs) have been investigated as diagnostic biomarkers, but substantial methodological variability across studies has limited the interpretation of current evidence. Previous meta-analyses largely evaluated miRNAs as a single biomarker category, leaving variation across biologically distinct subgroups insufficiently explored.</p><p><strong>Methods: </strong>Following PRISMA 2020 and PRISMA-DTA 2018 guidelines, we systematically searched PubMed, EMBASE, and Scopus through April 2026. Study quality was assessed using QUADAS-2, and pooled diagnostic performance was analyzed using a hierarchical summary receiver operating characteristic (HSROC) model. Subgroup analyses explored clinical, methodological, and functional sources of heterogeneity.</p><p><strong>Results: </strong>Thirty-nine studies involving 59 distinct miRNAs were included. Pooled sensitivity was 0.79 (95% CI: 0.76-0.82) and specificity was 0.82 (95% CI: 0.78-0.85), with an AUROC of 0.87 (95% CI: 0.84-0.90). Substantial heterogeneity was observed (sensitivity I<sup>2</sup> = 92.4%; specificity I<sup>2</sup> = 89.0%). In exploratory functional subgroup analyses, IL-1β-associated miRNAs demonstrated higher overall diagnostic accuracy (AUROC 0.90, 95% CI: 0.87-0.92), while endothelial dysfunction-related miRNAs showed comparatively higher specificity.</p><p><strong>Conclusion: </strong>Circulating miRNAs demonstrate moderate diagnostic accuracy for sepsis, with functional subgroup analyses showing differences across biologically distinct miRNA categories. Diagnostic performance appears to vary according to both biological function and methodological context. Substantial heterogeneity limits the generalizability of current evidence. Future multicenter studies using standardized protocols and infected non-septic control groups are needed to determine the clinical utility of pathway-specific miRNA panels.</p>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":" ","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Microbiology Immunology and Infection","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jmii.2026.06.004","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Sepsis diagnosis remains challenging, and conventional biomarkers such as CRP and PCT show limited specificity. Circulating microRNAs (miRNAs) have been investigated as diagnostic biomarkers, but substantial methodological variability across studies has limited the interpretation of current evidence. Previous meta-analyses largely evaluated miRNAs as a single biomarker category, leaving variation across biologically distinct subgroups insufficiently explored.
Methods: Following PRISMA 2020 and PRISMA-DTA 2018 guidelines, we systematically searched PubMed, EMBASE, and Scopus through April 2026. Study quality was assessed using QUADAS-2, and pooled diagnostic performance was analyzed using a hierarchical summary receiver operating characteristic (HSROC) model. Subgroup analyses explored clinical, methodological, and functional sources of heterogeneity.
Results: Thirty-nine studies involving 59 distinct miRNAs were included. Pooled sensitivity was 0.79 (95% CI: 0.76-0.82) and specificity was 0.82 (95% CI: 0.78-0.85), with an AUROC of 0.87 (95% CI: 0.84-0.90). Substantial heterogeneity was observed (sensitivity I2 = 92.4%; specificity I2 = 89.0%). In exploratory functional subgroup analyses, IL-1β-associated miRNAs demonstrated higher overall diagnostic accuracy (AUROC 0.90, 95% CI: 0.87-0.92), while endothelial dysfunction-related miRNAs showed comparatively higher specificity.
Conclusion: Circulating miRNAs demonstrate moderate diagnostic accuracy for sepsis, with functional subgroup analyses showing differences across biologically distinct miRNA categories. Diagnostic performance appears to vary according to both biological function and methodological context. Substantial heterogeneity limits the generalizability of current evidence. Future multicenter studies using standardized protocols and infected non-septic control groups are needed to determine the clinical utility of pathway-specific miRNA panels.
期刊介绍:
Journal of Microbiology Immunology and Infection is an open access journal, committed to disseminating information on the latest trends and advances in microbiology, immunology, infectious diseases and parasitology. Article types considered include perspectives, review articles, original articles, brief reports and correspondence.
With the aim of promoting effective and accurate scientific information, an expert panel of referees constitutes the backbone of the peer-review process in evaluating the quality and content of manuscripts submitted for publication.