Development of LncRNA Biomarkers in Extracellular Vesicle of Amniotic Fluid Associated with Antenatal Hydronephrosis.

Abstract

Background: Antenatal hydronephrosis (ANH) is the most common congenital renal and urinary tract anomaly, and parenchymal damage and renal fibrosis due to pathological hydronephrosis are the main causes of end-stage renal disease in children and chronic kidney disease in adults. At present, there is no validated biomarker for ANH, and diagnostic criteria other than prenatal ultrasonography (US) assessment are lacking. Therefore, we assessed to determine if biomarkers extracted from amniotic fluid small extracellular vesicles (sEVs) might be used as ANH diagnosis. Methods: With congenital ureteropelvic junction obstruction (UPJO) as the ultimate diagnosis, 10 pregnant women with Grade III-IV ANH and 10 normal pregnant women were recruited. The sEVs were extracted from amniotic fluid supernatant of all samples. Transcriptomic sequencing of sEVs in the discovery cohort identified the differential expression profiles for ANH. The known differentially expressed lncRNAs (DE-lncRNAs) were assessed by qRT-PCR in the validation cohort. Results: We explored the global RNA expression in sEVs from amniotic fluid. The differential expression profiles of both mRNAs and lncRNAs were related to fetal kidney development. Six known DE-lncRNAs were identified for ANH, and three of those with high expression were verified in more ANH samples. In particular, the upregulated LINC02863 and its target genes were associated with renal development and morphogenesis. The four predicted novel lncRNAs in high expression were also related to mesenchymal morphogenesis and the STAT3 signaling pathway and may play roles in ANH. Conclusions: We identified differentially expressed RNAs of all species in the sEVs from amniotic fluid, and the validated known DE-lncRNAs might serve as promising diagnostic biomarkers for ANH.