Proteomic Profiling in Patients With Peripartum Cardiomyopathy: A Biomarker Study of the ESC EORP PPCM Registry
Vitaris Kodogo1, Charle Viljoen2, Julian Hoevelmann3
1Cape Heart Institute, Faculty of Health Sciences, University of Cape Town, South Africa.
Insights
Peripartum cardiomyopathy (PPCM) is a serious condition affecting mothers. Researchers identified novel protein biomarkers in the blood to help diagnose PPCM more accurately and understand its causes.
Area of Science:
- Cardiology
- Proteomics
- Biomarker Discovery
Background:
- Peripartum cardiomyopathy (PPCM) is a significant global cause of maternal morbidity and mortality.
- Its underlying pathophysiology is not fully understood, leading to diagnostic challenges.
Purpose of the Study:
- To explore the serum proteome profile in newly diagnosed PPCM patients.
- To identify novel protein biomarkers for improved understanding of PPCM pathogenesis and diagnostic precision.
Main Methods:
- Untargeted serum proteome profiling using LC-MS/MS on 84 PPCM patients and 29 healthy controls.
- Differential protein expression analysis using Student's t-tests and Boruta algorithm.
- Diagnostic performance evaluation via AUC and 10-fold cross-validation.
Main Results:
- Identified 15 upregulated and 14 downregulated proteins in PPCM patients versus controls.
- Seven proteins were identified as significant by the Boruta algorithm.
- A combination of four proteins (adiponectin, QSOX1, ITI heavy chain, NT-proBNP) showed high diagnostic precision (AUC: 0.90).
Conclusions:
- Biologic themes in PPCM include immune response, inflammation, fibrosis, angiogenesis, apoptosis, and coagulation.
- Newly identified proteins require further investigation for their role in PPCM pathogenesis.
- These proteins may serve as potential diagnostic markers for PPCM.
Background:
Peripartum cardiomyopathy (PPCM) remains an important cause of maternal morbidity and mortality globally. The pathophysiology remains incompletely understood, and the diagnosis is often missed or delayed.
Objectives:
This study explored the serum proteome profile of patients with newly diagnosed PPCM, as compared with matched healthy postpartum mothers, to unravel novel protein biomarkers that would further an understanding of the pathogenesis of PPCM and improve diagnostic precision.
Methods:
Study investigators performed untargeted serum proteome profiling using data-independent acquisition-based label-free quantitative liquid chromatography-tandem mass spectrometry on 84 patients with PPCM, as compared with 29 postpartum healthy controls (HCs). Significant changes in protein intensities were determined with nonpaired Student's t-tests and were further classified by using the Boruta algorithm. The proteins' diagnostic performance was evaluated by area under the curve (AUC) and validated using the 10-fold cross-validation.
Results:
Patients with PPCM presented with a mean left ventricular ejection fraction of 33.5% ± 9.3% vs 57.0% ± 8.8% in HCs (P < 0.001). Study investigators identified 15 differentially up-regulated and 14 down-regulated proteins in patients with PPCM compared with HCs. Seven of these proteins were recognized as significant by the Boruta algorithm. The combination of adiponectin, quiescin sulfhydryl oxidase 1, inter-α-trypsin inhibitor heavy chain, and N-terminal pro-B-type natriuretic peptide had the best diagnostic precision (AUC: 0.90; 95% CI: 0.84-0.96) to distinguish patients with PPCM from HCs.
Conclusions:
Salient biologic themes related to immune response proteins, inflammation, fibrosis, angiogenesis, apoptosis, and coagulation were predominant in patients with PPCM compared with HCs. These newly identified proteins warrant further evaluation to establish their role in the pathogenesis of PPCM and potential use as diagnostic markers.
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