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Purpose <p>Circular RNAs (circRNAs), generated by backsplicing, are stable closed-loop RNAs. CircRNAs in amniotic fluid (AF) may serve as diagnostic and prognostic markers for Congenital Diaphragmatic Hernia (CDH). This study profiled AF circRNAs from CDH pregnancies to explore associations with CDH pathways and survival.</p> Methods <p>AF was collected from CDH pregnancies undergoing fetoscopic endoluminal tracheal occlusion (FETO) (n = 8; 4 survivors, 4 non-survivors). CircRNAs were profiled using the Arraystar Human circRNA Array V2. Differential expression was analyzed with <i>limma</i> in R and compared to our previously published data from CDH lungs. Parental genes underwent gene ontology and KEGG analyses, and selected circRNAs were validated by sequencing of backsplice junctions.</p> Results <p>A total of 10,760 circRNAs were detected in AF, 12,055 in mid-gestation lung, and 10,118 in late-gestation lung. In AF, 514 circRNAs were differentially expressed (False Discovery Rate (FDR) &lt; 0.05) with overlapping circRNAs, including 24 with late-gestation lung and 4 with CDH-related genes. CircFOXP2 (12-19) and circSMARCC1 (16-14) were validated. Parental genes of these differentially expressed AF circRNAs were enriched in specific molecular and signaling pathways.</p> Conclusions <p>AF circRNAs distinguish CDH survivors from non-survivors, mapping to genes and pathways critical for development, suggesting their diagnostic and prognostic potential.</p>

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Profiling circular RNAs in amniotic fluid and fetal lungs from congenital diaphragmatic hernia cases: insights into potential prognostic and diagnostic applications

  • 期刊论文

  • 发表日期：

    2026年3月16日

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  • Nolan S. De Leon,
  • Arzu Öztürk,
  • Francesca M. Russo,
  • Wai Hei Tse,
  • Claire McCallum,
  • Benjamin Eyrikson,
  • Jodi Qiao,
  • Daywin Patel,
  • Richard LeDuc,
  • Jan A. Deprest,
  • Richard Keijzer

摘要

Purpose

Circular RNAs (circRNAs), generated by backsplicing, are stable closed-loop RNAs. CircRNAs in amniotic fluid (AF) may serve as diagnostic and prognostic markers for Congenital Diaphragmatic Hernia (CDH). This study profiled AF circRNAs from CDH pregnancies to explore associations with CDH pathways and survival.

Methods

AF was collected from CDH pregnancies undergoing fetoscopic endoluminal tracheal occlusion (FETO) (n = 8; 4 survivors, 4 non-survivors). CircRNAs were profiled using the Arraystar Human circRNA Array V2. Differential expression was analyzed with limma in R and compared to our previously published data from CDH lungs. Parental genes underwent gene ontology and KEGG analyses, and selected circRNAs were validated by sequencing of backsplice junctions.

Results

A total of 10,760 circRNAs were detected in AF, 12,055 in mid-gestation lung, and 10,118 in late-gestation lung. In AF, 514 circRNAs were differentially expressed (False Discovery Rate (FDR) < 0.05) with overlapping circRNAs, including 24 with late-gestation lung and 4 with CDH-related genes. CircFOXP2 (12-19) and circSMARCC1 (16-14) were validated. Parental genes of these differentially expressed AF circRNAs were enriched in specific molecular and signaling pathways.

Conclusions

AF circRNAs distinguish CDH survivors from non-survivors, mapping to genes and pathways critical for development, suggesting their diagnostic and prognostic potential.