Wang Wei, Cui Hao, Ran Gao, Du Chuhao, Chen Xiao, Dong Shuo, Huang Siyuan, Yan Jun, Chu Junmin, Song Jiangping
Department of Cardiovascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing 100037, China.
The Cardiomyopathy Research Group, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing 100037, China.
Clin Chim Acta. 2023 Aug 1;548:117522. doi: 10.1016/j.cca.2023.117522. Epub 2023 Aug 19.
Tetralogy of Fallot (TOF) is a common congenital heart disease with high mortality. However, the medical imageology and liquidbiopsy techniques present certain limitations. Thus, this study investigated the plasma metabolic profiles to distinguish key metabolites for early diagnosis of TOF.
In total, 69 patients with TOF and 43 normal controls were enrolled for targeted metabolomics based on liquid chromatography-tandem mass spectroscopy (LC-MS/MS). Absolute quantification of metabolites was performed using our standard database. The differentially expressed metabolites (DEMs) were screened by fold change (FC), VIP value and pearson correlation coefficient of OPLS-DA model. Receiver operating characteristic curve (ROC) was used to evaluate predictive ability of DEMs.
Different metabolic profiles were presented between TOF and Normal.The pathway analysis showed that significantly changed metabolites were enriched in nicotinamide and purine metabolism. Many intermediatesproductof purine and amido acid were higher in TOF than in Normal group, while energy substrates and electron carriers were lower in TOF than in Normal group. ROC analysis revealed a high diagnostic value of plasma FAD for differentiating TOF from Normal (AUC = 1).
Our study quantitatively characterized plasma metabolites in patients with TOF and may help to develop reliable biomarkers that contribute to the early TOF screening.
法洛四联症（TOF）是一种常见的先天性心脏病，死亡率高。然而，医学影像学和液体活检技术存在一定局限性。因此，本研究调查了血浆代谢谱，以鉴别用于TOF早期诊断的关键代谢物。
共纳入69例TOF患者和43例正常对照，基于液相色谱-串联质谱（LC-MS/MS）进行靶向代谢组学研究。使用我们的标准数据库对代谢物进行绝对定量。通过倍数变化（FC）、VIP值和OPLS-DA模型的皮尔逊相关系数筛选差异表达代谢物（DEM）。采用受试者工作特征曲线（ROC）评估DEM的预测能力。
TOF组和正常组呈现出不同的代谢谱。通路分析表明，显著变化的代谢物在烟酰胺和嘌呤代谢中富集。TOF组中许多嘌呤和氨基酸的中间产物高于正常组，而能量底物和电子载体则低于正常组。ROC分析显示血浆FAD对区分TOF和正常组具有较高的诊断价值（AUC = 1）。
我们的研究对TOF患者的血浆代谢物进行了定量表征，可能有助于开发可靠的生物标志物，有助于TOF的早期筛查。
