Evaluation Of Circulating Placenta-related Long Noncoding RNAs As Potential Biomarkers For Preeclampsia

ObjectivesThe purpose of this study was to test the expression of circulating placenta-related long noncoding RNAs(lncRNAs)in preeclampsia(PE)and normal human pregnancy,and to assess them as potential biomarkers for PE.Methods1.The study included the following sets of cases and controls:(1)52 LOPE patients(diagnosed after 34 weeks)and 52 gestational age(GA)-matched controls;(2)58 EOPE patients(diagnosed before 34 weeks)and 58 GA-matched controls;and(3)30 healthy never-pregnant women.2.Dysregulated lncRNA between paired placental tissues from LOPE patients and matched controls were screened by lncRNA microarray.On the basis of the lncRNA microarray results,nine of differentially expressed lncRNA on the array platform were selected,and then subjected to quantitative reverse transcription-polymerase chain reaction(qRT-PCR)validation in placental tissues.3.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway were applied to explore the roles of the differentially expressed lncRNA,and to analyses the pathogenesis and development of PE.4.qRT-PCR was used to examine lncRNA expression levels in paired plasma samples from PE patients matched controls,and to analyses correlation of circulating placenta-related lncRNA levels between plasma and placenta and diagnostic power as potential biomarkers for detecting PE.5.ISH(in situ hybridization)was used to identify the localization of circulating placenta-related lncRNA in placenta,and futher explore the pathogenesis and development of PE.Results1.Using microarray analysis,we identified 163 lncRNA that were differentially expressed in placental samples from patients with LOPE,some of which were involved in the pathogenesis of PE.2.Placenta-related lncRNA were also detectable in plasma samples from pregnant women,and there were significant positive correlations between plasma and placental expression levels of the lncRNA NONHSAT116812 and NONHSAT145880.3.Strong separation was found between receiver operating characteristic(ROC)curves from PE patients and healthy controls.Circulating placenta-related lncRNA in plasma provided high diagnostic efficiencies for late-and EOPE.4.Circulating placenta-related lncRNA in human placenta were mainly located in the vascular endothelial cells and smooth muscle cells in placental villi.ConclusionsAberrantly expressed placenta-related lncRNA might play a key or partial role in the pathogenesis of PE.More importantly,circulating placenta-related lnc RNA,particularly NONHSAT116812 and NONHSAT145880 have high diagnostic power for the detection of LOPE and EOPE.Furtherly,prospective cohort studies are needed to validate these findings and to determine the clinical applicability of using circulating placenta-related RNAs as novel biomarkers for PE.