Accuracy of circulating microRNAs in diagnosis of sepsis: a systematic review and meta-analysis

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Accuracy of circulating microRNAs in diagnosis of sepsis: a systematic review and meta-analysis Xiaomin Shen1, Jiajie Zhang2, Yicheng Huang2, Jiepeng Tong1, Li Zhang1, Zhijuan Zhang1, Wei Yu1* and Yunqing Qiu1*

Abstract Objectives: The aim of this study was to systematically assess the accuracy of circulating microRNAs (miRNAs) as a promising biomarker for sepsis via a meta-analysis. Methods: PubMed, 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. Results: A 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. Conclusions: Our meta-analysis indicated that the level of circulating miRNAs, particularly the miR-223, could be used as an indicator for sepsis. Keywords: Sepsis, SIRS, miRNAs, Diagnosis, Biomarkers

* Correspondence: [email protected]; [email protected] 1 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If