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

Author:

Morey Robert1ORCID,Poling Lara1ORCID,Srinivasan Srimeenakshi1,Martinez-King Carolina1ORCID,Anyikam Adanna1,Zhang-Rutledge Kathy1ORCID,To Cuong1,Hakim Abbas1ORCID,Mochizuki Marina1,Verma Kajal1ORCID,Mason Antoinette1,Tran Vy1,Meads Morgan2ORCID,Lamale-Smith Leah1,Roeder Hilary1,Horii Mariko2ORCID,Ramos Gladys A.1ORCID,DeHoff Peter1ORCID,Parast Mana M.2,Pantham Priyadarshini1,Laurent Louise C.1ORCID

Affiliation:

1. Department of Obstetrics, Gynecology and Reproductive Medicine, University of California, San Diego, La Jolla, CA, USA.

2. Department of Pathology, University of California, San Diego, La Jolla, CA, USA.

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%).

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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