Abstract
Preeclampsia is one of the most dangerous pregnancy complications, and the leading cause of maternal and perinatal mortality and morbidity. Although the clinical symptoms appear late, its origin is early, and hence detection is feasible already at the first trimester. In the current study, we investigated the abundance of circulating small non-coding RNAs in the plasma of pregnant women in their first trimester, seeking transcripts that best separate the preeclampsia samples from those of healthy pregnant women. To this end, we performed small non-coding RNAs sequencing of 75 preeclampsia and control samples, and identified 25 transcripts that were differentially expressed between preeclampsia and the control groups. Furthermore, we utilized those transcripts and created a pipeline for a supervised classification of preeclampsia. Our pipeline generates a logistic regression model using a 5-fold cross validation on numerous random partitions into training and blind test sets. Using this classification procedure, we achieved an average AUC value of 0.86. These findings suggest the predictive value of circulating small non-coding RNA in the first trimester, warranting further examination, and lay the foundation for producing a novel early non-invasive diagnostic tool for preeclampsia, which could reduce the life-threatening risk for both the mother and fetus.
Highlights
Preeclampsia is one of the most dangerous pregnancy complications, and the leading cause of maternal and perinatal mortality and morbidity
Other small ncRNAs include: Small nucleolar RNA, which modulate the biogenesis and activity of ribosomes by post-transcriptional modifications of ribosomal RNA28,29; Small nuclear RNA, which facilitates mRNA splicing and regulate transcription initiation[30,31]; and Transfer RNA - the most abundant small ncRNA - which play a role in translation[32]
We investigated the abundance of circulating small ncRNAs in the plasma of pregnant women in their first trimester, seeking transcripts that best separate the PE samples from those of healthy pregnant women, and can serve as potential biomarkers for preeclampsia early diagnosis
Summary
Preeclampsia is one of the most dangerous pregnancy complications, and the leading cause of maternal and perinatal mortality and morbidity. Two tRNA types (tRNAVal and tRNAGly) were found to inhibit angiogenesis by modulating the function of endothelial cells[69], and misregulation of tRNAs and snRNAs was detected in cells cultured under hypoxic conditions[70] Overall, those and other accumulating evidences suggest that miRNAs as well as other small ncRNAs may have a role in PE development and can be potential biomarkers for PE early diagnosis. We investigated the abundance of circulating small ncRNAs in the plasma of pregnant women in their first trimester, seeking transcripts that best separate the PE samples from those of healthy pregnant women, and can serve as potential biomarkers for preeclampsia early diagnosis
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