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

作者：Siqi Bao, Tong Zhou, Congcong Yan, Jiale Bao, Fan Yang, Shan Chao, Meng Zhou, Zhangye Xu · 发表于：BMC Medicine · 年份：2022 · DOI：10.1186/s12916-022-02495-x · 被引用次数：29 · 研究领域：Pregnancy and preeclampsia studies、MicroRNA in disease regulation、Reproductive System and Pregnancy

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-invasi...