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BMC Medicine
Published in: BMC Medicine 1/2022

Open Access 01-12-2022 | Pre-Eclampsia | Research article

A blood-based miRNA signature for early non-invasive diagnosis of preeclampsia

Authors: Siqi Bao, Tong Zhou, Congcong Yan, Jiale Bao, Fan Yang, Shan Chao, Meng Zhou, Zhangye Xu

Published in: BMC Medicine | Issue 1/2022

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Abstract

Background

Preeclampsia (PE) is a multisystemic maternal syndrome with substantial maternal and fetal morbidity and mortality. Currently, there is no clinically viable non-invasive biomarker assay for early detection, thus limiting the effective prevention and therapeutic strategies for PE.

Methods

We conducted a discovery–training–validation three-phase retrospective and prospective study with cross-platform and multicenter cohorts. The initial biomarkers were discovered and verified in tissue specimens by small RNA sequencing and qRT-PCR. A miRNA signature (miR2PE-score) was developed using Firth’s bias-reduced logistic regression analysis and subsequently validated in two independent multinational retrospective cohorts and two prospective plasma cohorts.

Results

We initially identified five PE-associated differentially expressed miRNAs from miRNA sequencing data and subsequently validated two miRNAs (miR-196b-5p and miR-584-5p) as robust biomarkers by association analysis with clinical characteristics and qRT-PCR in tissue specimens in the discovery phase. Using Firth’s bias-reduced logistic regression analysis, we developed the miR2PE-score for the early detection of PE. The miR2PE-score showed a high diagnostic performance with an area under the receiver operating characteristic curve (AUROC) of 0.920, 0.848, 0.864, and 0.812 in training, internal, and two external validation cross-platform and multicenter cohorts, respectively. Finally, we demonstrated the non-invasive diagnostic performance of the miR2PE-score in two prospective plasma cohorts with AUROC of 0.933 and 0.787. Furthermore, the miR2PE-score revealed superior performance in non-invasive diagnosis compared with previously published miRNA biomarkers.

Conclusions

We developed and validated a novel and robust blood-based miRNA signature, which may serve as a promising clinically applicable non-invasive tool for the early detection of PE.

Graphical Abstract

Appendix
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Metadata
Title
A blood-based miRNA signature for early non-invasive diagnosis of preeclampsia
Authors
Siqi Bao
Tong Zhou
Congcong Yan
Jiale Bao
Fan Yang
Shan Chao
Meng Zhou
Zhangye Xu
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-022-02495-x

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