Identification of potential early biomarkers of preeclampsia

Placenta. 2018 Jan;61:61-71. doi: 10.1016/j.placenta.2017.11.011. Epub 2017 Nov 21.

Abstract

Introduction: It is thought that poor placental perfusion caused by inadequate remodelling of the maternal spiral arteries leads to preeclampsia (PE). To identify novel signalling pathways that contribute to PE pathogenesis and to create prerequisites for the non-invasive diagnosis of PE before clinical manifestations of the disease, this study aimed to evaluate miRNA expression levels in the placenta and blood plasma of pregnant women.

Methods: miRNA deep sequencing followed by real-time quantitative RT-PCR was applied to compare miRNA expression profiles in the placenta and blood plasma from women with early- and late-onset PE relative to the control group.

Results: A more than two-fold decrease in miR-532-5p, -423-5p, -127-3p, -539-5p, -519a-3p, and -629-5p and let-7c-5p expression levels was observed in the placenta, while a more than two-fold increase in miR-423-5p, 519a-3p, and -629-5p and let-7c-5p was observed in the blood plasma of pregnant women with PE. The above-listed miRNAs are associated with PE for the first time in this study, except for miR-519a-3p, whose role in PE has already been postulated. Using a logistic regression, plasma samples were classified into the early-onset PE group (probability p = 0.01, 80% specificity, 87.5% sensitivity and 87.5% precision) and showed increased miR-423-5p expression levels that were confirmed by the 9.8-fold up-regulation (р = 0.0002498) of miR-423-5p expression observed in the blood plasma at 11-13 GW by RT-PCR in a group of pregnant women manifesting severe PE clinical signs at 28-33 GW.

Conclusions: miR-423-5p may be considered a potential candidate for the early diagnosis of PE during the targeted management of high-risk pregnancies.

Keywords: Blood plasma; NGS; Placenta; Preeclampsia; RT-PCR; miRNA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Cesarean Section
  • Cohort Studies
  • Early Diagnosis
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Maternal Serum Screening Tests
  • MicroRNAs / blood*
  • MicroRNAs / chemistry
  • MicroRNAs / metabolism
  • Middle Aged
  • Placenta / metabolism*
  • Pre-Eclampsia / blood*
  • Pre-Eclampsia / diagnosis
  • Pre-Eclampsia / metabolism
  • Pre-Eclampsia / physiopathology
  • Pregnancy
  • Retrospective Studies
  • Sensitivity and Specificity
  • Sequence Analysis, RNA
  • Severity of Illness Index
  • Up-Regulation*

Substances

  • Biomarkers
  • MIRN423 microRNA, human
  • MicroRNAs