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Background <p>Preeclampsia (PE) is a hypertensive disorder complicating pregnancy characterized by new-onset hypertension occurring after 20 weeks of gestation, accompanied by at least one sign of end-organ damage. It poses significant risks to maternal and fetal health. Identifying reliable biomarkers is therefore critical for improving clinical outcomes.</p> Methods <p>In this study, we employed a bioinformatics approach to identify critical biomarkers associated with PE. Differential analysis was performed using the GSE66273 dataset obtained from the GEO database. A LASSO diagnostic model was constructed based on differentially expressed Neutrophil Extracellular Traps (NETs) genes, and external validation was conducted using GSE75010, GSE44711, and GSE173193 datasets. Immuno-infiltration analysis, functional enrichment analysis, and potential drug predictions were performed utilizing the Connectivity Map (CMap) database.</p> Results <p>We identified 30 differentially expressed NETs genes, and a LASSO regression revealed four genes with significant differences, namely Leptin (LEP), Plasminogen Activator Tissue (PLAT), Laminin Subunit Gamma 2 (LAMC2) and Amyloid Beta Precursor Protein (APP). Receiver Operating Characteristic (ROC) curve analysis demonstrated that the model built with these four key genes effectively predicted the occurrence of PE. The t-SNE algorithm showed significant differences in the expression levels of LEP, PLAT, LAMC2, and APP in different immune cells, and RT-qPCR experiments demonstrated that their transcriptional levels were significantly increased in the PE model mice. Meanwhile, these four key genes exhibited a significant correlation with immune cell content and enriched multiple KEGG signaling pathways. Additionally, CMap results suggested the potential reversal of PE by four drugs, including ISOX, HC-toxin, Vorinostat, and Bis-tyrphostin.</p> Conclusion <p>Our study provides novel insights and clinical therapeutic options for the prevention and management of PE.</p>

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Identification and analysis of potential biomarkers for preeclampsia in neutrophil extracellular traps

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月30日

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  • Jia Li,
  • Zhe Yin,
  • Ying Zhang,
  • Tao Chen

摘要

Background

Preeclampsia (PE) is a hypertensive disorder complicating pregnancy characterized by new-onset hypertension occurring after 20 weeks of gestation, accompanied by at least one sign of end-organ damage. It poses significant risks to maternal and fetal health. Identifying reliable biomarkers is therefore critical for improving clinical outcomes.

Methods

In this study, we employed a bioinformatics approach to identify critical biomarkers associated with PE. Differential analysis was performed using the GSE66273 dataset obtained from the GEO database. A LASSO diagnostic model was constructed based on differentially expressed Neutrophil Extracellular Traps (NETs) genes, and external validation was conducted using GSE75010, GSE44711, and GSE173193 datasets. Immuno-infiltration analysis, functional enrichment analysis, and potential drug predictions were performed utilizing the Connectivity Map (CMap) database.

Results

We identified 30 differentially expressed NETs genes, and a LASSO regression revealed four genes with significant differences, namely Leptin (LEP), Plasminogen Activator Tissue (PLAT), Laminin Subunit Gamma 2 (LAMC2) and Amyloid Beta Precursor Protein (APP). Receiver Operating Characteristic (ROC) curve analysis demonstrated that the model built with these four key genes effectively predicted the occurrence of PE. The t-SNE algorithm showed significant differences in the expression levels of LEP, PLAT, LAMC2, and APP in different immune cells, and RT-qPCR experiments demonstrated that their transcriptional levels were significantly increased in the PE model mice. Meanwhile, these four key genes exhibited a significant correlation with immune cell content and enriched multiple KEGG signaling pathways. Additionally, CMap results suggested the potential reversal of PE by four drugs, including ISOX, HC-toxin, Vorinostat, and Bis-tyrphostin.

Conclusion

Our study provides novel insights and clinical therapeutic options for the prevention and management of PE.