ItemArticle

Large-Scale Proteomics Reveals New Candidate Biomarkers for Late-Onset Preeclampsia

Title
Large-Scale Proteomics Reveals New Candidate Biomarkers for Late-Onset Preeclampsia
Creator
Andresen, Ina J.; Romero, Roberto; Westerberg, Ane C.; Than, Ndor Gor; Gomez-Lopez, Nardhy; Bhatti, Gaurav; Ahmodu, Oladejo; Gudicha, Dereje W.; Meyyazhagan, Arun; Awonuga, Awoniyi; Chaiworapongsa, Tinnakorn; Bryant, David R.; Michelsen, Trond M.; Tarca, Adi L.
Description
BACKGROUND: Preeclampsia is classified as either a more severe early onset or a more prevalent late-onset form. Lower PlGF (placental growth factor) and increased sFlt-1 (fms-like tyrosine kinase-1) in maternal circulation are promising biomarkers, yet they lack specificity for preeclampsia. METHODS: We quantified ?7000 proteins in 673 samples collected from 89 patients with late-onset preeclampsia and 91 controls at T1 (1522), T2 (2230), and T3 (3042) weeks. Elastic net and random forest models were fitted and evaluated by cross-validation. Differential abundance analysis followed by functional profiling, was used to identify and interpret protein changes. RESULTS: An increase in protein differential abundance in late-onset preeclampsia was observed with advancing gestation, reaching 806 proteins at T3 related to angiogenesis, cell adhesion, and extracellular matrix remodeling. FAAH2 (fatty acid amide hydrolase 2), SIGLEC6 (sialic acid-binding Ig-like lectin-6), IL17RC (interleukin-17 receptor C), HTRA1 (serine protease), sFlt-1, and 47 other proteins dysregulated at T3 were validated in a reanalysis of a ?5000 protein Norwegian data set. Random forest models with 20 proteins showed high accuracy at T3 (area under the curve [AUC], 0.83 [0.770.89], sensitivity 59%) even in cases not yet diagnosed at sampling (n=31, AUC, 0.80 [0.710.90], sensitivity 58%), outperforming sFlt-1 and PlGF. Moderate accuracy was obtained at T1 (AUC, 0.63 [0.540.72], sensitivity 33%) and T2 (AUC, 0.59 [0.500.68], sensitivity 17%). Combining maternal characteristics and obstetric history with proteomics data increased accuracy at T1 (AUC, 0.68 [0.590.77], sensitivity 28%), T2 (AUC, 0.68 [0.600.77], sensitivity 31%), and T3 (AUC, 0.87 [0.810.92], sensitivity 69%). CONCLUSIONS: The findings confirm the involvement of abnormal trophoblast invasion, angiogenesis, and extracellular matrix remodeling in late-onset preeclampsia, while highlighting new protein alterations consistent across diverse cohorts. 2025 American Heart Association, Inc.
Source
Hypertension;Volume;83;Issue;2;
Date
01-01-2026
Publisher
Lippincott Williams and Wilkins
Subject
biomarkers; humans; pregnancy; proteomics; random forest
Coverage
Andresen I.J., Department of Obstetrics, Division of Obstetrics and Gynecology, Oslo University Hospital Rikshospitalet, Norway; Romero R., Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, United States, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, United States, Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (R.R.), United States; Westerberg A.C., Department of Obstetrics, Division of Obstetrics and Gynecology, Oslo University Hospital Rikshospitalet, Norway; Than N.G., Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, United States, Systems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary, Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary, Maternity Private Clinic of Obstetrics and Gynecology, Budapest, Hungary, Genesis Theranostix Group, Budapest, Hungary; Gomez-Lopez N., Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States, Center for Reproductive Health Sciences, Departments of Obstetrics and Gynecology and Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States; Bhatti G., Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United States; Ahmodu O., Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United States; Gudicha D.W., Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, United States; Meyyazhagan A., Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States, Department of Life Sciences, Christ University, Bengaluru, India; Awonuga A., Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States; Chaiworapongsa T., Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States; Bryant D.R., Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States; Michelsen T.M., Department of Obstetrics, Division of Obstetrics and Gynecology, Oslo University Hospital Rikshospitalet, Norway, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Tarca A.L., Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States, Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United States
Rights
All Open Access; Green Open Access
Relation
ISSN: 0194911X; CODEN: HPRTD
Format
online
Language
English
Type
Article

Citation

Andresen, Ina J.; Romero, Roberto; Westerberg, Ane C.; Than, Ndor Gor; Gomez-Lopez, Nardhy; Bhatti, Gaurav; Ahmodu, Oladejo; Gudicha, Dereje W.; Meyyazhagan, Arun; Awonuga, Awoniyi; Chaiworapongsa, Tinnakorn; Bryant, David R.; Michelsen, Trond M.; Tarca, Adi L., “Large-Scale Proteomics Reveals New Candidate Biomarkers for Late-Onset Preeclampsia,” CHRIST (Deemed To Be University) Institutional Repository, accessed June 19, 2026, https://archives.christuniversity.in/items/show/23094.

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