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Published on: January 26, 2024
Systematic Proteome Profiling of Maternal Plasma for Development of Preeclampsia Biomarkers
Ji Hyae Lim1, Jae Min Lim2, Hyeong Min Lee2
1Smart MEC Healthcare R&D Center, CHA Future Medicine Research Institute, CHA Bundang Medical Center, Seongnam, Republic of Korea.
Insights
Researchers identified three plasma biomarkers, APOM, LCN2, and QSOX1, for preeclampsia (PE) detection. These novel biomarkers show high accuracy, offering a potential new way to assess PE independent of clinical symptoms.
Area of Science:
- Proteomics
- Biomarker Discovery
- Maternal Health
Background:
- Preeclampsia (PE) is a pregnancy-specific hypertensive disorder.
- Current diagnostic markers like blood pressure and proteinuria have limited predictive value for adverse outcomes.
- There is a critical need for more effective diagnostic biomarkers for PE.
Purpose of the Study:
- To identify novel, clinically effective diagnostic biomarkers for preeclampsia using systematic proteome profiling.
- To validate the diagnostic accuracy of identified protein biomarkers in independent cohorts.
Main Methods:
- Plasma samples from pregnant women with and without PE underwent TMT-based liquid chromatography-mass spectrometry (LC-MS/MS) for proteome profiling.
- Differentially expressed proteins (DEPs) were identified and functionally annotated using bioinformatic tools.
- Candidate biomarkers were validated using multiple reaction monitoring (MRM) analysis and ELISA in an independent cohort.
Main Results:
- A total of 1307 proteins were identified, with 138 DEPs (71 upregulated, 67 downregulated) found in PE patients compared to controls.
- Upregulated proteins were linked to platelet degranulation, proteolysis, and lipid metabolism; downregulated proteins to blood coagulation and acute-phase response.
- APOM, LCN2, and QSOX1 demonstrated high diagnostic accuracy (AUC >0.9) for PE detection in validation cohorts.
Conclusions:
- Systematic proteomic profiling identified APOM, LCN2, and QSOX1 as promising plasma biomarkers for preeclampsia.
- These biomarkers offer high diagnostic accuracy, potentially enabling PE assessment independent of clinical presentation.
- Further validation and clinical implementation of these biomarkers could improve maternal health outcomes.
Abstract:
Preeclampsia (PE) is a hypertensive disorder of pregnancy with various clinical symptoms. However, traditional markers for the disease including high blood pressure and proteinuria are poor indicators of the related adverse outcomes. Here, we performed systematic proteome profiling of plasma samples obtained from pregnant women with PE to identify clinically effective diagnostic biomarkers. Proteome profiling was performed using TMT-based liquid chromatography-mass spectrometry (LC-MS/MS) followed by subsequent verification by multiple reaction monitoring (MRM) analysis on normal and PE maternal plasma samples. Functional annotations of differentially expressed proteins (DEPs) in PE were predicted using bioinformatic tools. The diagnostic accuracies of the biomarkers for PE were estimated according to the area under the receiver-operating characteristics curve (AUC). A total of 1307 proteins were identified, and 870 proteins of them were quantified from plasma samples. Significant differences were evident in 138 DEPs, including 71 upregulated DEPs and 67 downregulated DEPs in the PE group, compared with those in the control group. Upregulated proteins were significantly associated with biological processes including platelet degranulation, proteolysis, lipoprotein metabolism, and cholesterol efflux. Biological processes including blood coagulation and acute-phase response were enriched for down-regulated proteins. Of these, 40 proteins were subsequently validated in an independent cohort of 26 PE patients and 29 healthy controls. APOM, LCN2, and QSOX1 showed high diagnostic accuracies for PE detection (AUC >0.9 and p < 0.001, for all) as validated by MRM and ELISA. Our data demonstrate that three plasma biomarkers, identified by systematic proteomic profiling, present a possibility for the assessment of PE, independent of the clinical characteristics of pregnant women.
