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Updated: Jul 1, 2025
TMT Sample Preparation for Proteomics Facility Submission and Subsequent Data Analysis
Published on: June 8, 2020
Proteomic analysis of plasma proteins from patients with cardiac rupture after acute myocardial infarction using
Jingyuan Hou1,2, Qiaoting Deng1, Xiaohong Qiu3
1Research Experimental Center, Meizhou Clinical Institute of Shantou University Medical College, Meizhou, Guangdong, 514031, China.
Insights
This study identified key plasma protein changes in cardiac rupture (CR) patients, revealing potential biomarkers like CRP, HSPB1, VINC, and GDF15 for improved diagnosis after acute myocardial infarction (AMI).
Area of Science:
- Proteomics
- Cardiovascular Medicine
- Biomarker Discovery
Background:
- Cardiac rupture (CR) is a rare but fatal complication of acute myocardial infarction (AMI).
- Reliable diagnostic biomarkers and underlying signaling pathways for CR remain unclear.
- Understanding CR mechanisms is crucial for improving patient outcomes.
Purpose of the Study:
- To comprehensively characterize plasma proteome alterations in patients with cardiac rupture.
- To identify potential protein biomarkers for the clinical diagnosis of CR.
- To gain insights into the molecular pathways involved in CR pathogenesis.
Main Methods:
- Quantitative proteomics using tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- Plasma samples analyzed from patients with CR (n=37), AMI (n=47), and healthy controls (n=47).
- Candidate protein validation using multiple reaction monitoring (MRM) and enzyme-linked immunosorbent assay (ELISA).
Main Results:
- 1208 proteins quantified, with 958 differentially expressed proteins (DEPs) identified.
- DEPs were significantly altered in CR patients compared to controls and AMI patients.
- Bioinformatics analysis implicated pathways like RNA transport, necroptosis, and leukocyte transendothelial migration in CR.
- Four proteins (CRP, HSPB1, VINC, GDF15) validated by ELISA showed high diagnostic accuracy (AUC=0.895) for distinguishing CR from AMI.
Conclusions:
- Comprehensive proteomic analysis is valuable for identifying plasma proteome changes in CR.
- This study provides a foundation for elucidating CR mechanisms and developing diagnostic biomarkers.
- The identified protein panel holds promise for aiding in the early diagnosis of cardiac rupture.
Background:
Cardiac rupture (CR) is a rare but catastrophic mechanical complication of acute myocardial infarction (AMI) that seriously threatens human health. However, the reliable biomarkers for clinical diagnosis and the underlying signaling pathways insights of CR has yet to be elucidated.
Methods:
In the present study, a quantitative approach with tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry was used to characterize the differential protein expression profiles of patients with CR. Plasma samples were collected from patients with CR (n = 37), patients with AMI (n = 47), and healthy controls (n = 47). Candidate proteins were selected for validation by multiple reaction monitoring (MRM) and enzyme-linked immunosorbent assay (ELISA).
Results:
In total, 1208 proteins were quantified and 958 differentially expressed proteins (DEPs) were identified. The difference in the expression levels of the DEPs was more noticeable between the CR and Con groups than between the AMI and Con groups. Bioinformatics analysis showed most of the DEPs to be involved in numerous crucial biological processes and signaling pathways, such as RNA transport, ribosome, proteasome, and protein processing in the endoplasmic reticulum, as well as necroptosis and leukocyte transendothelial migration, which might play essential roles in the complex pathological processes associated with CR. MRM analysis confirmed the accuracy of the proteomic analysis results. Four proteins i.e., C-reactive protein (CRP), heat shock protein beta-1 (HSPB1), vinculin (VINC) and growth/differentiation factor 15 (GDF15), were further validated via ELISA. By receiver operating characteristic (ROC) analysis, combinations of these four proteins distinguished CR patients from AMI patients with a high area under the curve (AUC) value (0.895, 95% CI, 0.802-0.988, p < 0.001).
Conclusions:
Our study highlights the value of comprehensive proteomic characterization for identifying plasma proteome changes in patients with CR. This pilot study could serve as a valid foundation and initiation point for elucidation of the mechanisms of CR, which might aid in identifying effective diagnostic biomarkers in the future.
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