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

• DOI: 10.1186/s12916-022-02495-x
• Publication Date: 2022-09-13T00:02:36Z
• Authors: Siqi Bao; Tong Zhou; Congcong Yan; Jiale Bao; Fan Yang; Shan Chao; Meng Zhou; Zhangye Xu
• Keywords: 0301 basic medicine; Liquid biopsy; R; MicroRNA; Biomarker; Early diagnosis; Preeclampsia; 3. Good health; MicroRNAs; 03 medical and health sciences; Pre-Eclampsia; Biomarkers, Tumor; Medicine; Humans; Female; Non-invasive; Prospective Studies; Research Article; Retrospective Studies

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