Discovery and verification of extracellular microRNA biomarkers for diagnostic and prognostic assessment of preeclampsia at triage

UCSD researchers report on the identification of extracellular miRNA (ex-miRNA) biomarkers for early diagnosis and prognosis of preeclampsia (PE). Small RNA sequencing of maternal serum prospectively collected from participants undergoing evaluation for suspected PE revealed distinct patterns of ex-miRNA expression among different categories of hypertensive disorders in pregnancy. Applying an iterative machine learning method identified three bivariate miRNA biomarkers that, when applied serially, distinguished between PE cases of different severity and differentiated cases from controls with a sensitivity of 93%, specificity of 79%, positive predictive value (PPV) of 55%, and negative predictive value (NPV) of 89%. In a small independent validation cohort, these ex-miRNA biomarkers had a sensitivity of 91% and specificity of 57%. Combining these ex-miRNA biomarkers with the established sFlt1:PlGF protein biomarker ratio performed better than either set of biomarkers alone (sensitivity of 89.4%, specificity of 91.3%, PPV of 95.5%, and NPV of 80.8%).

Expression of the 110 verified candidate bivariate extracellular miRNA (ex-miRNA) biomarkers

Heatmap displaying the log ratio of the 110 verified candidate bivariate ex-miRNA biomarkers. Both bivariate ex-miRNAs (y axis) and samples (x axis) are clustered using hierarchical clustering. Color bars at the top of the heatmap display sample metadata and show strong separation of the samples by overall diagnosis (case versus control; n = 71 and n = 52, respectively), by detailed diagnoses, and by interval between blood draw and preeclampsia (PE) diagnosis, but not by cohort (discovery versus verification; n = 82 and n = 41, respectively) or gestational age at blood draw (GABD). No patients were included in multiple classifications. Blue boxes with letters mark sample clusters discussed in the text. Bivariate ex-miRNA biomarkers clustered by the presence of a particular ex-miRNA biomarker in the ratio and by location in the genome as shown on the y axis.

Morey R, Poling L, Srinivasan S, Martinez-King C, Anyikam A, Zhang-Rutledge K, To C, Hakim A, Mochizuki M, Verma K, Mason A, Tran V, Meads M, Lamale-Smith L, Roeder H, Horii M, Ramos GA, DeHoff P, Parast MM, Pantham P, Laurent LC. (2023) Discovery and verification of extracellular microRNA biomarkers for diagnostic and prognostic assessment of preeclampsia at triage. Sci Adv 9(51):eadg7545. [article]

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