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Published on: December 9, 2022
MicroRNAs in sepsis diagnosis: A systematic review and meta-analysis toward evidence-based biomarker development
Shu-Hui Chen1, Sameer Noor2, Wei-Hsuan Liu3
1Department of Emergency Medicine, Keelung Chang Gung Memorial Hospital, No. 222, Maijin Rd., Anle District, Keelung City, 204, Taiwan, ROC.
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.
Insights
Circulating microRNAs show moderate accuracy for diagnosing sepsis, but performance varies by biological function and study methods. Further research with standardized protocols is needed to confirm their clinical utility.
Area of Science:
- Biomarker discovery
- Molecular diagnostics
- Sepsis research
Background:
- Sepsis diagnosis is challenging, with limited specificity of conventional biomarkers like C-reactive protein (CRP) and procalcitonin (PCT).
- Circulating microRNAs (miRNAs) are explored as diagnostic biomarkers, but methodological variability hinders interpretation.
- Previous meta-analyses treated miRNAs as a single category, overlooking variations in distinct biological subgroups.
Purpose of the Study:
- To systematically evaluate the diagnostic performance of circulating miRNAs for sepsis.
- To explore heterogeneity in diagnostic accuracy across different miRNA subgroups and methodological factors.
- To identify potential for pathway-specific miRNA panels in sepsis diagnostics.
Main Methods:
- Systematic literature search of PubMed, EMBASE, and Scopus adhering to PRISMA 2020 and PRISMA-DTA 2018 guidelines.
- Quality assessment using QUADAS-2 and pooled diagnostic performance analysis via a hierarchical summary receiver operating characteristic (HSROC) model.
- Subgroup analyses to investigate clinical, methodological, and functional sources of heterogeneity.
Main Results:
- Thirty-nine studies including 59 distinct miRNAs were analyzed.
- Pooled sensitivity was 0.79 (95% CI: 0.76-0.82) and specificity was 0.82 (95% CI: 0.78-0.85), with an area under the receiver operating characteristic curve (AUROC) of 0.87 (95% CI: 0.84-0.90).
- Significant heterogeneity was observed. Interleukin-1 beta (IL-1β)-associated miRNAs showed higher AUROC (0.90), while endothelial dysfunction-related miRNAs exhibited higher specificity.
Conclusions:
- Circulating miRNAs offer moderate diagnostic accuracy for sepsis, with performance varying by biological function and methodology.
- Substantial heterogeneity limits the generalizability of current evidence.
- Future multicenter studies with standardized protocols and appropriate control groups are essential to establish the clinical utility of pathway-specific miRNA panels.