Discovery and verification of extracellular microRNA biomarkers for diagnostic and prognostic assessment of preeclampsia at triage
Robert Morey, Lara Poling, Srimeenakshi Srinivasan, Carolina Martinez-King, Adanna Anyikam, Kathy Zhang‐Rutledge, Cuong To, Abbas Hakim, Marina Mochizuki, Kajal Verma, Antoinette Mason, Vy Tran, Morgan Meads, Leah Lamale‐Smith, Hilary Roeder, Mariko Horii, Gladys Ramos, Peter DeHoff, Mana M. Parast, Priyadarshini Pantham, Louise C. Laurent
Abstract
We 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 ( miR-522-3p/miR-4732-5p , miR-516a-5p/miR-144-3p , and miR-27b-3p/let-7b-5p ) 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%).