Large-scale prospective serum metabolomic profiling reveals candidate predictive biomarkers for suspected preeclampsia patients

Abstract Preeclampsia (PE) is a serious pregnancy complication that contributes to maternal and perinatal morbidity and mortality. Understanding its pathogenesis and revealing predictive biomarkers are essential for guiding treatment decisions. In order to explore the global changes of serum metabol...

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Main Authors: Yan Cao, Lanlan Meng, Yifei Wang, Shenglong Zhao, Yuanyuan Zheng, Rui Ran, Jie Du, Hongqiang Wu, Jiaqi Han, Zhengwen Xu, Yifan Lu, Lin Liu, Lu Chen, Jing Wang, Youran Li, Yanhong Zhai, Zhi Sun, Zheng Cao
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Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-87905-9
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author Yan Cao
Lanlan Meng
Yifei Wang
Shenglong Zhao
Yuanyuan Zheng
Rui Ran
Jie Du
Hongqiang Wu
Jiaqi Han
Zhengwen Xu
Yifan Lu
Lin Liu
Lu Chen
Jing Wang
Youran Li
Yanhong Zhai
Zhi Sun
Zheng Cao
author_facet Yan Cao
Lanlan Meng
Yifei Wang
Shenglong Zhao
Yuanyuan Zheng
Rui Ran
Jie Du
Hongqiang Wu
Jiaqi Han
Zhengwen Xu
Yifan Lu
Lin Liu
Lu Chen
Jing Wang
Youran Li
Yanhong Zhai
Zhi Sun
Zheng Cao
author_sort Yan Cao
collection DOAJ
description Abstract Preeclampsia (PE) is a serious pregnancy complication that contributes to maternal and perinatal morbidity and mortality. Understanding its pathogenesis and revealing predictive biomarkers are essential for guiding treatment decisions. In order to explore the global changes of serum metabolites in PE patients and identify potential predictive biomarkers for suspected PE patients (pregnant women who had already shown PE-related symptoms in the middle to late stages of pregnancy, but were not yet confirmatively diagnosed as PE.), a large-scale serum metabolomic analysis was conducted in this study with a prospective cohort of 328 suspected PE patients in the middle or late pregnancy stages, as well as a retrospective cohort of 30 healthy pregnant women and 30 PE patients. Using liquid chromatography mass spectrometry (LC − MS), serum metabolomic profiling revealed that the development of PE was closely associated with disturbed amino acid metabolism. Moreover, a panel of seven predictive biomarkers including 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate, gamma-glutamyl-leucine, 2-hydroxyvaleric acid, LysoPC(16:1(9Z)/0:0), PC(DiMe(13,5)/MonoMe(13,5)), ADP-D-glycero-beta-D-manno-heptose and phenylalanyl-tryptophan were identified for PE development by performing multiple statistical analysis and LASSO regression analysis. The combination of these biomarkers showed promise in the prediction of PE development for suspected PE patients, with an AUC of 0.753 and 0.885 for the discovery and validation cohorts, respectively. These findings highlight the potential of large-scale prospective metabolomic studies combined with machine learning algorithms in identifying key biomarkers for predicting PE development, while retrospective metabolomics studies provide insights into the pathogenesis of PE.
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spelling doaj-art-fdcda2335dde4162bac3c5a8097247a12025-02-09T12:30:51ZengNature PortfolioScientific Reports2045-23222025-02-0115111110.1038/s41598-025-87905-9Large-scale prospective serum metabolomic profiling reveals candidate predictive biomarkers for suspected preeclampsia patientsYan Cao0Lanlan Meng1Yifei Wang2Shenglong Zhao3Yuanyuan Zheng4Rui Ran5Jie Du6Hongqiang Wu7Jiaqi Han8Zhengwen Xu9Yifan Lu10Lin Liu11Lu Chen12Jing Wang13Youran Li14Yanhong Zhai15Zhi Sun16Zheng Cao17Department of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji UniversityDepartment of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalBiotree Metabolomics Technology Research CenterBiotree Metabolomics Technology Research CenterBiotree Metabolomics Technology Research CenterDepartment of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalAbstract Preeclampsia (PE) is a serious pregnancy complication that contributes to maternal and perinatal morbidity and mortality. Understanding its pathogenesis and revealing predictive biomarkers are essential for guiding treatment decisions. In order to explore the global changes of serum metabolites in PE patients and identify potential predictive biomarkers for suspected PE patients (pregnant women who had already shown PE-related symptoms in the middle to late stages of pregnancy, but were not yet confirmatively diagnosed as PE.), a large-scale serum metabolomic analysis was conducted in this study with a prospective cohort of 328 suspected PE patients in the middle or late pregnancy stages, as well as a retrospective cohort of 30 healthy pregnant women and 30 PE patients. Using liquid chromatography mass spectrometry (LC − MS), serum metabolomic profiling revealed that the development of PE was closely associated with disturbed amino acid metabolism. Moreover, a panel of seven predictive biomarkers including 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate, gamma-glutamyl-leucine, 2-hydroxyvaleric acid, LysoPC(16:1(9Z)/0:0), PC(DiMe(13,5)/MonoMe(13,5)), ADP-D-glycero-beta-D-manno-heptose and phenylalanyl-tryptophan were identified for PE development by performing multiple statistical analysis and LASSO regression analysis. The combination of these biomarkers showed promise in the prediction of PE development for suspected PE patients, with an AUC of 0.753 and 0.885 for the discovery and validation cohorts, respectively. These findings highlight the potential of large-scale prospective metabolomic studies combined with machine learning algorithms in identifying key biomarkers for predicting PE development, while retrospective metabolomics studies provide insights into the pathogenesis of PE.https://doi.org/10.1038/s41598-025-87905-9PreeclampsiaSerum metabolomic studyPredictive biomarkersAltered metabolic pathwaysMachine learning algorithms
spellingShingle Yan Cao
Lanlan Meng
Yifei Wang
Shenglong Zhao
Yuanyuan Zheng
Rui Ran
Jie Du
Hongqiang Wu
Jiaqi Han
Zhengwen Xu
Yifan Lu
Lin Liu
Lu Chen
Jing Wang
Youran Li
Yanhong Zhai
Zhi Sun
Zheng Cao
Large-scale prospective serum metabolomic profiling reveals candidate predictive biomarkers for suspected preeclampsia patients
Scientific Reports
Preeclampsia
Serum metabolomic study
Predictive biomarkers
Altered metabolic pathways
Machine learning algorithms
title Large-scale prospective serum metabolomic profiling reveals candidate predictive biomarkers for suspected preeclampsia patients
title_full Large-scale prospective serum metabolomic profiling reveals candidate predictive biomarkers for suspected preeclampsia patients
title_fullStr Large-scale prospective serum metabolomic profiling reveals candidate predictive biomarkers for suspected preeclampsia patients
title_full_unstemmed Large-scale prospective serum metabolomic profiling reveals candidate predictive biomarkers for suspected preeclampsia patients
title_short Large-scale prospective serum metabolomic profiling reveals candidate predictive biomarkers for suspected preeclampsia patients
title_sort large scale prospective serum metabolomic profiling reveals candidate predictive biomarkers for suspected preeclampsia patients
topic Preeclampsia
Serum metabolomic study
Predictive biomarkers
Altered metabolic pathways
Machine learning algorithms
url https://doi.org/10.1038/s41598-025-87905-9
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