Department of Infectious Diseases, the Second Affiliated Hospital of Nanchang University, School of Pharmaceutical Science , Nanchang University , Nanchang 330006 , P. R. China.
Medical College of Nanchang University , Nanchang University , Nanchang 330006 , P. R. China.
J Proteome Res. 2018 Oct 5;17(10):3517-3525. doi: 10.1021/acs.jproteome.8b00466. Epub 2018 Sep 19.
To identify and screen serum biomarkers to determine pediatric patients with congenital heart diseases (PCH) from healthy control children (NC), a total of 614 clinically diagnosed subjects from three hospitals, including 491 PCH and 234 NC, were enrolled for nontargeted proton nuclear magnetic resonance spectroscopy (H NMR)-based and targeted ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS)-based metabolomics studies. Nineteen serum metabolites distinguishing PCH from NC were identified by H NMR-based metabolomic analysis. The amino acid and choline metabolic pathways were considered to be closely related to PCH. The serum levels of 13 metabolites in these two pathways were further determined by UPLC-MS/MS and observed to be altered significantly in PCH. Taurine, glutamine, and glutamate presented considerable diagnostic value for the diagnosis of PCH (AUROC > 0.80). Logistic regression analysis showed that a combination of four variables, namely, betaine, taurine, glutamine, and phenylalanine, yields a high diagnostic value (AUROC = 0.949) and prediction accuracy (89.1%) for differentiating PCH from the NC, and the sensitivity and specificity were 93.9 and 95.2%, respectively. Further double-blind sample prediction showed that the accuracy of the model was 83.8% for 80 unknown samples. Our results showed that the serum amino acid and choline metabolite levels in PCH were changed considerably. The combination of four metabolites, namely, betaine, taurine, glutamine, and phenylalanine, can be used as potential serum biomarkers in PCH diagnosis, which contributes to the early PCH screening.
为了鉴定和筛选血清生物标志物，以区分先天性心脏病（PCH）患儿和健康对照儿童（NC），我们对来自三家医院的共 614 例临床确诊的研究对象进行了非靶向质子核磁共振波谱（1H NMR）和靶向超高效液相色谱-串联质谱（UPLC-MS/MS）代谢组学研究，其中包括 491 例 PCH 和 234 例 NC。通过 1H NMR 代谢组学分析，鉴定出 19 种能区分 PCH 和 NC 的血清代谢物。氨基酸和胆碱代谢途径被认为与 PCH 密切相关。通过 UPLC-MS/MS 进一步测定了这两条通路中 13 种代谢物的血清水平，发现它们在 PCH 中明显改变。牛磺酸、谷氨酰胺和谷氨酸对 PCH 的诊断具有相当大的价值（AUROC＞0.80）。逻辑回归分析表明，贝丁酸、牛磺酸、谷氨酰胺和苯丙氨酸这四个变量的组合具有较高的诊断价值（AUROC=0.949）和预测准确性（89.1%），用于区分 PCH 和 NC，灵敏度和特异性分别为 93.9%和 95.2%。进一步的双盲样本预测表明，该模型对 80 个未知样本的准确率为 83.8%。我们的研究结果表明，PCH 患儿血清氨基酸和胆碱代谢物水平发生了明显变化。贝丁酸、牛磺酸、谷氨酰胺和苯丙氨酸这四种代谢物的组合可作为 PCH 诊断的潜在血清生物标志物，有助于早期 PCH 筛查。
