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Discovery and Verification of Extracellular miRNA Biomarkers for Non-invasive Prediction of Pre-eclampsia in Asymptomatic Women

2020; Elsevier BV; Volume: 1; Issue: 2 Linguagem: Inglês

10.1016/j.xcrm.2020.100013

2666-3791

Srimeenakshi Srinivasan, Ryan Treacy, Tiffany Herrero, Richelle Olsen, Trevor R. Leonardo, Xuan Zhang, Peter DeHoff, Cuong To, Lara Poling, Aileen Fernando, Sandra Leon-Garcia, Katharine Knepper, Vy Tran, Morgan Meads, Jennifer Tasarz, Aishwarya Vuppala, Soojin Park, Clara D. Laurent, Tony Bui, Pike-See Cheah, Rachael Overcash, Gladys A. Ramos, Hilary Roeder, Ionita Ghiran, Mana M. Parast, Xandra O. Breakefield, Amir J. Lueth, Sharon R. Rust, Max T. Dufford, Angela Fox, Durlin E. Hickok, Julja Burchard, J. Jay Boniface, Louise C. Laurent, Kim Boggess, George R. Saade, Scott Sullivan, Glenn Markenson, Jay D. Iams, Dean V. Coonrod, Leonardo Pereira, M. Sean Esplin, Larry Cousins, Garrett Lam, Matthew Hoffman,

Reproductive System and Pregnancy

Development of effective prevention and treatment strategies for pre-eclampsia is limited by the lack of accurate methods for identification of at-risk pregnancies. We performed small RNA sequencing (RNA-seq) of maternal serum extracellular RNAs (exRNAs) to discover and verify microRNAs (miRNAs) differentially expressed in patients who later developed pre-eclampsia. Sera collected from 73 pre-eclampsia cases and 139 controls between 17 and 28 weeks gestational age (GA), divided into separate discovery and verification cohorts, are analyzed by small RNA-seq. Discovery and verification of univariate and bivariate miRNA biomarkers reveal that bivariate biomarkers verify at a markedly higher rate than univariate biomarkers. The majority of verified biomarkers contain miR-155-5p, which has been reported to mediate the pre-eclampsia-associated repression of endothelial nitric oxide synthase (eNOS) by tumor necrosis factor alpha (TNF-α). Deconvolution analysis reveals that several verified miRNA biomarkers come from the placenta and are likely carried by placenta-specific extracellular vesicles.