Maternal plasma microRNA signatures for early detection of early-onset preeclampsia.

Early-onset preeclampsia (EOPE) is a severe pregnancy complication associated with an increased risk of maternal and fetal morbidity and mortality. Given the lack of a cure, accurate and non-invasive biomarkers are urgently needed for early diagnosis and effective management. Here, we performed transcriptomic profiling of maternal peripheral blood miRNAs using small RNA sequencing and identified 51 dysregulated plasma miRNAs associated with EOPE. Among them, miR-144-5p and miR-486-5p were validated as potential biomarkers in the tissue sample cohort. We developed a two-miRNA signature (cMiR2EO) using a logistic regression model in the plasma discovery cohort, which achieved excellent performance in discriminating EOPE from controls (AUC = 0.950). The cMiR2EO was further validated in an independent plasma cohort using qRT-PCR (AUC = 0.782), and two public tissue sample cohorts (AUCs =0.896 and 0.657), and our in-house tissue cohort (AUC = 0.754). Additionally, the cMiR2EO offers a significant benefit over current clinical screening approaches used for EOPE detection. In vitro assays verified that both miR-486-5p and miR-144-5p actively promote trophoblastic cell migration and invasion. Our study demonstrates the potential of plasma miRNA expression as a non-invasive tool for EOPE detection. The identified two-miRNA panel holds promise for improving patient outcomes by enabling earlier intervention in EOPE cases.