Dataset Information

Peripheral blood cell microRNA quantification during the first trimester predicts preeclampsia: Proof of concept.

ABSTRACT:

Objective

We investigated the capacity of microRNAs isolated from peripheral blood buffy coat collected late during the first trimester to predict preeclampsia.

Study design

The cohort study comprised 48 pregnant women with the following pregnancy outcomes: 8 preeclampsia and 40 with normal delivery outcomes. Quantitative rtPCR was performed on a panel of 30 microRNAs from buffy coat samples drawn at a mean of 12.7±0.5 weeks gestation. MicroRNA Risk Scores were calculated and AUC-ROC calculations derived.

Results

The AUC-ROC for preeclampsia risk was 0.91 (p<0.0001). When women with normal delivery and high-risk background (those with SLE/APS, chronic hypertension and/or Type 2 Diabetes) were compared to women who developed preeclampsia but with a normal risk background (without these mentioned risk factors), preeclampsia was still predicted with an AUC-ROC of 0.92 (p<0.0001).

Conclusion

MicroRNA quantification of peripheral immune cell microRNA provides sensitive and specific prediction of preeclampsia in the first trimester of pregnant women. With this study, we extend the range during which disorders of the placental bed may be predicted from early to the end of the first trimester. This study confirms that buffy coat may be used as a sample preparation.

SUBMITTER: Winger EE

PROVIDER: S-EPMC5749845 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Peripheral blood cell microRNA quantification during the first trimester predicts preeclampsia: Proof of concept.

Winger Edward E EE Reed Jane L JL Ji Xuhuai X Nicolaides Kypros K

PloS one 20180102 1

<h4>Objective</h4>We investigated the capacity of microRNAs isolated from peripheral blood buffy coat collected late during the first trimester to predict preeclampsia.<h4>Study design</h4>The cohort study comprised 48 pregnant women with the following pregnancy outcomes: 8 preeclampsia and 40 with normal delivery outcomes. Quantitative rtPCR was performed on a panel of 30 microRNAs from buffy coat samples drawn at a mean of 12.7±0.5 weeks gestation. MicroRNA Risk Scores were calculated and AUC- ...[more]

PMID: 29293682

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Project description:Preeclampsia (PE) is a complex and multifaceted obstetric syndrome characterized by several distinct molecular subtypes. It complicates up to 5% of pregnancies and significantly contributes to maternal and newborn morbidity, thereby diminishing the long-term quality of life for affected women. Due to the widespread dissatisfaction with the effectiveness of existing approaches for assessing PE risk, there is a pressing need for ongoing research to identify newer, more accurate predictors. This study aimed to investigate early changes in the maternal serum proteome and associated signaling pathways. The levels of 125 maternal serum proteins at 11-13 weeks of gestation were quantified using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM MS) with the BAK-125 kit. Ten serum proteins emerged as potential early markers for PE: Apolipoprotein M (APOM), Complement C1q subcomponent subunit B (C1QB), Lysozyme (LYZ), Prothrombin (F2), Albumin (ALB), Zinc-alpha-2-glycoprotein (AZGP1), Tenascin-X (TNXB), Alpha-1-antitrypsin (SERPINA1), Attractin (ATRN), and Apolipoprotein A-IV (APOA4). Notably, nine of these proteins have previously been associated with PE in prior research, underscoring the consistency and reliability of our findings. These proteins play key roles in critical molecular processes, including complement and coagulation cascades, platelet activation, and insulin-like growth factor pathways. To improve the early prediction of PE, a highly effective Support Vector Machine (SVM) model was developed, analyzing 19 maternal serum proteins from the first trimester. This model achieved an area under the curve (AUC) of 0.91, with 87% sensitivity and 95% specificity, and a hazard ratio (HR) of 13.5 (4.6-40.8) with p < 0.001. These findings demonstrate that serum protein-based SVM models possess significantly higher predictive power compared to the routine first-trimester screening test, highlighting their superior utility in the early detection and risk stratification of PE.

Project description:IntroductionPreeclampsia (PE) is a severe obstetrical syndrome characterized by new-onset hypertension and proteinuria and it is often associated with fetal intrauterine growth restriction (IUGR). PE leads to long-term health complications, so early diagnosis would be crucial for timely prevention. There are multiple etiologies and subtypes of PE, and this heterogeneity has hindered accurate identification in the presymptomatic phase. Recent investigations have pointed to the potential role of small regulatory RNAs in PE, and these species, which travel in extracellular vesicles (EVs) in the circulation, have raised the possibility of non-invasive diagnostics. The aim of this study was to investigate the behavior of exosomal regulatory small RNAs in the most severe subtype of PE with IUGR.MethodsWe isolated exosomal EVs from first-trimester peripheral blood plasma samples of women who later developed preterm PE with IUGR (n=6) and gestational age-matched healthy controls (n=14). The small RNA content of EVs and their differential expression were determined by next-generation sequencing and further validated by quantitative real-time PCR. We also applied the rigorous exceRpt bioinformatics pipeline for small RNA identification, followed by target verification and Gene Ontology analysis.ResultsOverall, >2700 small RNAs were identified in all samples and, of interest, the majority belonged to the RNA interference (RNAi) pathways. Among the RNAi species, 16 differentially expressed microRNAs were up-regulated in PE, whereas up-regulated and down-regulated members were equally found among the six identified Piwi-associated RNAs. Gene ontology analysis of the predicted small RNA targets showed enrichment of genes in pathways related to immune processes involved in decidualization, placentation and embryonic development, indicating that dysregulation of the induced small RNAs is connected to the impairment of immune pathways in preeclampsia development. Finally, the subsequent validation experiments revealed that the hsa_piR_016658 piRNA is a promising biomarker candidate for preterm PE associated with IUGR.DiscussionOur rigorously designed study in a homogeneous group of patients unraveled small RNAs in circulating maternal exosomes that act on physiological pathways dysregulated in preterm PE with IUGR. Therefore, our small RNA hits are not only suitable biomarker candidates, but the revealed biological pathways may further inform us about the complex pathology of this severe PE subtype.

Dataset Information

Peripheral blood cell microRNA quantification during the first trimester predicts preeclampsia: Proof of concept.

Objective

Study design

Results

Conclusion

Publications

Peripheral blood cell microRNA quantification during the first trimester predicts preeclampsia: Proof of concept.

Similar Datasets

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