• Large-Scale Proteomics Reveals...

*Result*: Large-Scale Proteomics Reveals New Candidate Biomarkers for Late-Onset Preeclampsia.

Title:
Large-Scale Proteomics Reveals New Candidate Biomarkers for Late-Onset Preeclampsia.
Authors:
Andresen IJ; Department of Obstetrics, Division of Obstetrics and Gynecology, Oslo University Hospital Rikshospitalet, Norway (I.J.A., A.C.W., T.M.M.)., 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 (R.R., N.G.-L., D.W.G.).; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor (R.R.).; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (R.R.)., Westerberg AC; Department of Obstetrics, Division of Obstetrics and Gynecology, Oslo University Hospital Rikshospitalet, Norway (I.J.A., A.C.W., T.M.M.)., Than NG; 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 (R.R., N.G.-L., D.W.G.).; Systems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary (N.G.T.).; Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary (N.G.T.).; Maternity Private Clinic of Obstetrics and Gynecology, Budapest, Hungary (N.G.T.).; Genesis Theranostix Group, Budapest, Hungary (N.G.T.)., Gomez-Lopez N; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI (N.G.-L., A.M., A.A., T.C., D.R.B., A.L.T.).; Center for Reproductive Health Sciences, Departments of Obstetrics and Gynecology and Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (N.G.-L.)., Bhatti G; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI (G.B., O.A., A.L.T.)., Ahmodu O; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI (G.B., O.A., A.L.T.)., Gudicha DW; 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 (R.R., N.G.-L., D.W.G.)., Meyyazhagan A; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI (N.G.-L., A.M., A.A., T.C., D.R.B., A.L.T.).; Department of Life Sciences, Christ University, Bengaluru, India (A.M.)., Awonuga A; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI (N.G.-L., A.M., A.A., T.C., D.R.B., A.L.T.)., Chaiworapongsa T; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI (N.G.-L., A.M., A.A., T.C., D.R.B., A.L.T.)., Bryant DR; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI (N.G.-L., A.M., A.A., T.C., D.R.B., A.L.T.)., Michelsen TM; Department of Obstetrics, Division of Obstetrics and Gynecology, Oslo University Hospital Rikshospitalet, Norway (I.J.A., A.C.W., T.M.M.).; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway (T.M.M.)., Tarca AL; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI (N.G.-L., A.M., A.A., T.C., D.R.B., A.L.T.).; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI (G.B., O.A., A.L.T.).
Source:
Hypertension (Dallas, Tex. : 1979) [Hypertension] 2026 Feb; Vol. 83 (2), pp. e25189. Date of Electronic Publication: 2025 Oct 01.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Lippincott, Williams & Wilkins Country of Publication: United States NLM ID: 7906255 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4563 (Electronic) Linking ISSN: 0194911X NLM ISO Abbreviation: Hypertension Subsets: MEDLINE
Imprint Name(s):
Publication: : Hagerstown, MD : Lippincott, Williams & Wilkins
Original Publication: [Dallas, Tex.] : [American Heart Association], [©1979]-
MeSH Terms:
Pre-Eclampsia*/diagnosis , Pre-Eclampsia*/blood , Pre-Eclampsia*/metabolism , Proteomics*/methods, Biomarkers/blood ; Biomarkers/metabolism ; Placenta Growth Factor/blood ; Vascular Endothelial Growth Factor Receptor-1/blood ; Humans ; Female ; Pregnancy ; Adult ; Gestational Age
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Grant Information:
HHSN275201300006C United States HD NICHD NIH HHS; R01 AI184481 United States AI NIAID NIH HHS; R21 HD115800 United States HD NICHD NIH HHS
Contributed Indexing:
Keywords: biomarkers; humans; pregnancy; proteomics; random forest
Substance Nomenclature:
0 (Biomarkers)
144589-93-5 (Placenta Growth Factor)
EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
Entry Date(s):
Date Created: 20251001 Date Completed: 20260121 Latest Revision: 20260123
Update Code:
20260130
PubMed Central ID:
PMC12614630
DOI:
10.1161/HYPERTENSIONAHA.125.25189
PMID:
41031401
Database:
MEDLINE

*Further Information*

*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 (15-22), T2 (22-30), and T3 (30-42) 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 [0.77-0.89], sensitivity 59%) even in cases not yet diagnosed at sampling (n=31, AUC, 0.80 [0.71-0.90], sensitivity 58%), outperforming sFlt-1 and PlGF. Moderate accuracy was obtained at T1 (AUC, 0.63 [0.54-0.72], sensitivity 33%) and T2 (AUC, 0.59 [0.50-0.68], sensitivity 17%). Combining maternal characteristics and obstetric history with proteomics data increased accuracy at T1 (AUC, 0.68 [0.59-0.77], sensitivity 28%), T2 (AUC, 0.68 [0.60-0.77], sensitivity 31%), and T3 (AUC, 0.87 [0.81-0.92], 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.*

*A.L. Tarca and R. Romero are listed as coinventors on a granted US patent titled Kits and methods for prediction and treatment of preeclampsia. The other authors report no conflicts.*