Cell Reports Medicine (May 2020)
Discovery and Verification of Extracellular miRNA Biomarkers for Non-invasive Prediction of Pre-eclampsia in Asymptomatic Women
- Srimeenakshi Srinivasan,
- Ryan Treacy,
- Tiffany Herrero,
- Richelle Olsen,
- Trevor R. Leonardo,
- Xuan Zhang,
- Peter DeHoff,
- Cuong To,
- Lara G. 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 Tabitha Overcash,
- Gladys A. Ramos,
- Hilary Roeder,
- Ionita Ghiran,
- Mana Parast,
- Xandra O. Breakefield,
- Amir J. Lueth,
- Sharon R. Rust,
- Max T. Dufford,
- Angela C. Fox,
- Durlin E. Hickok,
- Julja Burchard,
- J. Jay Boniface,
- Louise C. Laurent,
- Kim A. Boggess,
- George R. Saade,
- Scott A. Sullivan,
- Glenn R. Markenson,
- Jay D. Iams,
- Dean V. Coonrod,
- Leonardo M. Pereira,
- M. Sean Esplin,
- Larry M. Cousins,
- Garrett K. Lam,
- Matthew K. Hoffman
Affiliations
- Srimeenakshi Srinivasan
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- Ryan Treacy
- Sera Prognostics, 2749 East Parleys Way, Salt Lake City, UT 84109, USA
- Tiffany Herrero
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA; Department of Obstetrics and Gynecology, Stanford University, Palo Alto, CA 94305, USA
- Richelle Olsen
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA; Franciscan Maternal-Fetal Medicine Associates at St. Joseph, Tacoma, WA 98405, USA
- Trevor R. Leonardo
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA; Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60607, USA
- Xuan Zhang
- Neurology and Radiology Services and Program in Neuroscience, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02115, USA
- Peter DeHoff
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- Cuong To
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- Lara G. Poling
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- Aileen Fernando
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- Sandra Leon-Garcia
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- Katharine Knepper
- Department of Pathology, University of California, San Diego, La Jolla, CA 92037, USA
- Vy Tran
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- Morgan Meads
- Department of Pathology, University of California, San Diego, La Jolla, CA 92037, USA
- Jennifer Tasarz
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- Aishwarya Vuppala
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- Soojin Park
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- Clara D. Laurent
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- Tony Bui
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- Pike See Cheah
- Neurology and Radiology Services and Program in Neuroscience, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02115, USA; Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia
- Rachael Tabitha Overcash
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- Gladys A. Ramos
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA
- Hilary Roeder
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA; Kaiser Permanente San Diego, San Diego, CA 92120, USA
- Ionita Ghiran
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
- Mana Parast
- Department of Pathology, University of California, San Diego, La Jolla, CA 92037, USA
- Xandra O. Breakefield
- Neurology and Radiology Services and Program in Neuroscience, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02115, USA
- Amir J. Lueth
- Sera Prognostics, 2749 East Parleys Way, Salt Lake City, UT 84109, USA
- Sharon R. Rust
- Sera Prognostics, 2749 East Parleys Way, Salt Lake City, UT 84109, USA
- Max T. Dufford
- Sera Prognostics, 2749 East Parleys Way, Salt Lake City, UT 84109, USA
- Angela C. Fox
- Sera Prognostics, 2749 East Parleys Way, Salt Lake City, UT 84109, USA
- Durlin E. Hickok
- Sera Prognostics, 2749 East Parleys Way, Salt Lake City, UT 84109, USA
- Julja Burchard
- Sera Prognostics, 2749 East Parleys Way, Salt Lake City, UT 84109, USA
- J. Jay Boniface
- Sera Prognostics, 2749 East Parleys Way, Salt Lake City, UT 84109, USA
- Louise C. Laurent
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA; Corresponding author
- Kim A. Boggess
- George R. Saade
- Scott A. Sullivan
- Glenn R. Markenson
- Jay D. Iams
- Dean V. Coonrod
- Leonardo M. Pereira
- M. Sean Esplin
- Larry M. Cousins
- Garrett K. Lam
- Matthew K. Hoffman
- Journal volume & issue
-
Vol. 1,
no. 2
p. 100013
Abstract
Summary: 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.
