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Background <p>Preeclampsia is a severe pregnancy-related disorder characterized by hypertension and proteinuria, and affects approximately 2–8% of pregnancies worldwide. It poses substantial risks to both maternal and fetal health, including preterm birth, intrauterine growth restriction, and life-threatening complications, such as eclampsia and organ failure. However, the mechanisms underlying preeclampsia, especially those involving blood-associated proteins, are poorly understood. This study aimed to identify critical blood proteins linked to severe preeclampsia and explore their potential mechanisms of action.</p> Materials and results <p>Twenty-two venous blood samples (14 from patients with severe preeclampsia (sPE) and 8 from matched healthy controls) were collected for comparative proteomic analysis using advanced astral mass spectrometry. Using exploratory machine learning approaches (random forest and OPLS-DA) as feature selection tools, 36 serum proteins were identified as the sole biomarkers that exhibited significant differences between patients with sPE and healthy controls in this discovery cohort. Among these, 30 serum proteins were technically validated by PRM within the same cohort, demonstrating consistent differential expression, and could be used as potential biomarkers for sPE. Moreover, untargeted serum metabolome analysis identified 14 differential serum metabolites, including protoporphyrin IX, hecogenin, and astragalin, phenylacetylglutamine, shikimic acid, and 4,5-dihydroorotic acid, that were enriched in healthy pregnant women and patients with sPE, respectively. Changes in serum proteins were correlated with shifts in the serum metabolome in patients with sPE, suggesting potential interrelationships that warrant further investigation.</p> Conclusions <p>Our research indicates that changes in serum metabolites, possibly due to the presence of serum proteins, such as ENG, may contribute to the development of sPE. This exploratory study provides preliminary insights into the interactions between serum proteins and metabolites in sPE. The findings highlight potential biomarker candidates and mechanistic pathways; however, further validation in larger cohorts is needed to confirm their diagnostic and therapeutic relevance.</p>

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Identifying biomarkers of the serum proteins and metabolites associated with severe preeclampsia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月11日

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  • Xianxian Liu,
  • Tian Lu,
  • Xiaoming Zeng,
  • Yang Hu,
  • Siming Xin,
  • Yu Chen,
  • Zhihong Hu,
  • Maolin Yu,
  • Yang Zou,
  • Xinwei Xiong

摘要

Background

Preeclampsia is a severe pregnancy-related disorder characterized by hypertension and proteinuria, and affects approximately 2–8% of pregnancies worldwide. It poses substantial risks to both maternal and fetal health, including preterm birth, intrauterine growth restriction, and life-threatening complications, such as eclampsia and organ failure. However, the mechanisms underlying preeclampsia, especially those involving blood-associated proteins, are poorly understood. This study aimed to identify critical blood proteins linked to severe preeclampsia and explore their potential mechanisms of action.

Materials and results

Twenty-two venous blood samples (14 from patients with severe preeclampsia (sPE) and 8 from matched healthy controls) were collected for comparative proteomic analysis using advanced astral mass spectrometry. Using exploratory machine learning approaches (random forest and OPLS-DA) as feature selection tools, 36 serum proteins were identified as the sole biomarkers that exhibited significant differences between patients with sPE and healthy controls in this discovery cohort. Among these, 30 serum proteins were technically validated by PRM within the same cohort, demonstrating consistent differential expression, and could be used as potential biomarkers for sPE. Moreover, untargeted serum metabolome analysis identified 14 differential serum metabolites, including protoporphyrin IX, hecogenin, and astragalin, phenylacetylglutamine, shikimic acid, and 4,5-dihydroorotic acid, that were enriched in healthy pregnant women and patients with sPE, respectively. Changes in serum proteins were correlated with shifts in the serum metabolome in patients with sPE, suggesting potential interrelationships that warrant further investigation.

Conclusions

Our research indicates that changes in serum metabolites, possibly due to the presence of serum proteins, such as ENG, may contribute to the development of sPE. This exploratory study provides preliminary insights into the interactions between serum proteins and metabolites in sPE. The findings highlight potential biomarker candidates and mechanistic pathways; however, further validation in larger cohorts is needed to confirm their diagnostic and therapeutic relevance.