Abstract

ObjectivesThe aim of this study was to systematically assess the accuracy of circulating microRNAs (miRNAs) as a promising biomarker for sepsis via a meta-analysis.MethodsPubMed, Cochrane Library, Embase, Web of Science, Scopus, and Ovid databases were searched up to April 3, 2020. The Quality in Prognostic Studies (QUADAS-2) tool was used to assess methodological quality. The pooled sensitivity (Sen), specificity (Spe), positive or negative likelihood ratios (PLR or NLR), diagnostic odds ratio (DOR), curve, and area under the curve (AUC) were calculated with 95% confidence interval (95% CI). The overall accuracy (OA) of miRNAs, procalcitonin (PCT), and C-reactive protein (CRP) was analyzed by the chi-square test.ResultsA total of 22 records were eligible for systematic review, including 2210 sepsis, 426 systemic inflammatory response syndrome (SIRS), and 1076 healthy controls (HC). The pooled Sen, Spe, and DOR of miRNAs were 0.80 (95% CI 0.75–0.83), 0.85 (95% CI 0.80–0.89), and 22 (15–32), respectively. The DOR of PCT and CRP were 17 (95% CI 4–68) and 7 (95% CI 1–48), respectively. The OA value of miRNAs (79.02%) and PCT (76.95%) were higher than CRP (61.22%) (P < 0.000). The subgroup analysis indicated that miRNAs in adults, serum type, downregulation of miRNA expression, criteria of Sepsis-3, internal reference of non-U6, and dysregulation expression of miR-223 had superior diagnostic accuracy. In addition, there was no significant publication bias among the included studies. Fagan’s nomogram showed valuable clinical utility.ConclusionsOur meta-analysis indicated that the level of circulating miRNAs, particularly the miR-223, could be used as an indicator for sepsis.

Highlights

  • Sepsis is defined as a life-threatening condition of organ dysfunction resulted from a dysregulated host response to infection [1]

  • Literatures were considered eligible for inclusion using the following criteria: (1) the target population consisted of one or more circulating miRNAs for sepsis; (2) sufficient data to generate true positive (Tp), true negative (Tn), false positive (Fp), and false negative (Fn) directly or indirectly; and (3) either retrospective or prospective design studies

  • The overall accuracy (OA) value of miRNAs (79.02%) and PCT (76.95%) were higher than C-reactive protein (CRP) (61.22%) (P < 0.000)

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Summary

Introduction

Sepsis is defined as a life-threatening condition of organ dysfunction resulted from a dysregulated host response to infection [1]. Recent epidemiologic data have shown an increasing incidence of sepsis and septic shock with high mortality [2]. Recent data suggested a declining trend in mortality, longer-term morbidity and decreased health-related quality of life remain a serious problem [3]. The clinical syndrome of sepsis is difficult to diagnose. A previous study reported 50% of patients with sepsis were not correctly classified in the USA [4]. Diagnosis of sepsis is crucial for improving the survival rate; traditional screening tools and biomarkers lack specificity [5]

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