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Large Scale Non-targeted Metabolomic Profiling of Serum by Ultra Performance Liquid Chromatography-Mass Spectrometry UPLC-MS
Published on: March 14, 2013
Metabolomic profile for the early detection of coronary artery disease by using UPLC-QTOF/MS
Xiaobao Xu1, Beibei Gao2, Qijie Guan1
1College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310027, China.
Insights
Novel metabolomic profiling accurately distinguishes patients with coronary artery disease (CAD) and acute myocardial infarction (AMI). Specific metabolites like ceramides and steroids show potential for improved CAD diagnosis and risk stratification.
Area of Science:
- Cardiovascular Disease Research
- Metabolomics
- Biomarker Discovery
Background:
- Traditional risk factors have limited predictive power for coronary artery disease (CAD).
- Acute myocardial infarction (AMI) often presents without prior warning symptoms.
- Novel diagnostic strategies are crucial for identifying patients at risk of acute coronary syndrome.
Purpose of the Study:
- To investigate the potential of non-targeted metabolomic profiling for differentiating CAD patient groups.
- To identify specific metabolites associated with the progression of CAD.
- To develop improved predictive criteria for CAD diagnosis and treatment.
Main Methods:
- Serum samples from stable angina, AMI, and healthy controls were analyzed using ultra-performance liquid chromatography coupled to time of flight mass spectrometry (UPLC-QTOF/MS).
- Multivariate statistical models, including orthogonal partial least squares-discriminant analysis (OPLS-DA), were employed for data analysis.
- Metabolomic profiles were validated using internal cross-validation methods, achieving an area under the receiver operating characteristic curve (AUROC) of 0.983.
Main Results:
- Distinct metabolomic profiles were observed between stable angina and AMI patients.
- Altered metabolites identified include phospholipids, fatty acids, sphingolipids, glycerolipids, and steroids.
- Specific metabolites such as ceramides (Cer(t18:0/16:0), Cer(d18:0/12:0)) and dehydroepiandrosterone sulfate were strongly associated with CAD progression.
Conclusions:
- Metabolomic profiling offers a powerful approach for distinguishing CAD patient states.
- Certain metabolites, particularly ceramides and steroids, demonstrate significant potential as predictive biomarkers for CAD.
- These findings support the development of more stringent and predictive diagnostic criteria for CAD.
Abstract:
Traditional risk factors cannot promote prediction capacity for the patients with coronary artery disease (CAD), who usually do not show apparent symptoms until they develop acute myocardial infarction (AMI). As such, novel predictive diagnostic strategies are essential to accurately define patients at risk of acute coronary syndrome. In this study, non-targeted metabolomic profiling using ultra-performance liquid chromatography coupled to time of flight mass spectrometry (UPLC-QTOF/MS) was performed in combination with multivariate statistical model to analyze the serum samples of patients with stable angina (n=38), acute myocardial infarction (AMI) (n=34) and healthy age- and gender-matched controls (n=71). Results showed a clear distinction in metabolomic profiles between stable angina and AMI when using OPLS-DA with both positive and negative models. Internal cross-validation methods were used to confirm model validity with an area under the curve (AUROC)=0.983. We identified various classes of altered metabolites including phospholipids, fatty acids, sphingolipids, glycerolipids and steroids. We then demonstrated the differential roles of these metabolites using multivariate statistical model. Phospholipids previously associated with CAD were shown to have lower predictive capacity to discriminate AMI patients from stable angina patients. Interestingly, ceramides, bile acid and steroids hormone such as Cer(t18:0/16:0), Cer(d18:0/12:0), dehydroepiandrosterone sulfate (VIP scores of 1.99, 1.97, 1.64, respectively), were found to be associated with the progression of CAD. These results suggest that metabolomic approaches may facilitate the development of more stringent and predictive patient criteria in the diagnosis and treatment of CAD.

