Serum Metabolomics Profiling to Identify Novel Biomarkers for Cyanotic Heart Disease

Abstract

Congenital heart disease (CHD) is one of the most important causes of the death of children and young adults. Most of the patients do not survive past their teen years. This occurs either due to delay in diagnosis or no diagnosis at all. In recent times, several studies have shown the importance of biomarkers in the prediction of such defects. These biomarkers give the real time snapshot of the on going processes inside the cells and can significantly support the diagnosis of CHD. The present experiment was designed as an observational single centre pilot study to identify and establish the diagnostic metabolic signatures associated with the congenital heart diseases. Metabolic profiles of sera collected from 35 cyanotic congenital heart disease patients and 15 controls were obtained using high-resolution 1D 1H CPMG and NMR spectra. The metabolic profiles were compared using multivariate statistical analysis to identify the disease specific metabolic disturbances associated with cyanotic heart disease. The results show perturbation in several metabolites in cyanotic CHD patients versus controls. The discriminatory metabolites were further analysedwith area under receiver operating characteristic (AUROC) curve and identified five metabolic entities (i.e.valine, glucose, glutamine, creatinineand PUFA) which could differentiate cyanotic CHDs from controls with higher specificity.In conclusion, untargeted metabolic approach proved to be helpful in identifying and differentiating disease causing metabolites in cyanotic cases from controls.