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

Authors
  • Morey, Robert
  • Poling, Lara
  • Srinivasan, Srimeenakshi
  • Martinez-King, Carolina
  • Anyikam, Adanna
  • Zhang-Rutledge, Kathy
  • To, Cuong
  • Hakim, Abbas
  • Mochizuki, Marina
  • Verma, Kajal
  • Mason, Antoinette
  • Tran, Vy
  • Meads, Morgan
  • Lamale-Smith, Leah
  • Roeder, Hilary
  • Horii, Mariko
  • Ramos, Gladys A
  • DeHoff, Peter
  • Parast, Mana M
  • Pantham, Priyadarshini
  • And 1 more
Publication Date
Dec 22, 2023
Source
eScholarship - University of California
Keywords
License
Unknown
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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%).

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