Graham Stewart F, Turkoglu Onur, Kumar Praveen, Yilmaz Ali, Bjorndahl Trent C, Han BeomSoo, Mandal Rupasri, Wishart David S, Bahado-Singh Ray O
Beaumont Health , 3811 W. 13 Mile Road, Royal Oak, Michigan 48073, United States.
Department of Biological and Computing Sciences, University of Alberta , Edmonton, Alberta T6G 2R3, Canada.
J Proteome Res. 2017 Jul 7;16(7):2587-2596. doi: 10.1021/acs.jproteome.7b00157. Epub 2017 Jun 20.
Currently little is known about the underlying pathophysiology associated with SIDS, and no objective biomarkers exist for the accurate identification of those at greatest risk of dying from SIDS. Using targeted metabolomics, we aim to profile the medulla oblongata of infants who have died from SIDS (n = 16) and directly compare their biochemical profile with age matched controls. Combining data acquired using H NMR and targeted DI-LC-MS/MS, we have identified fatty acid oxidation as a pivotal biochemical pathway perturbed in the brains of those infants who have from SIDS (p = 0.0016). Further we have identified a potential central biomarker with an AUC (95% CI) = 0.933 (0.845-1.000) having high sensitivity (0.933) and specificity (0.875) values for discriminating between control and SIDS brains. This is the first reported study to use targeted metabolomics for the study of PM brain from infants who have died from SIDS. We have identified pathways associated with the disease and central biomarkers for early screening/diagnosis.
目前，关于婴儿猝死综合征（SIDS）潜在的病理生理学知之甚少，且不存在用于准确识别SIDS死亡风险最高人群的客观生物标志物。我们旨在通过靶向代谢组学对死于SIDS的婴儿（n = 16）的延髓进行分析，并将其生化特征与年龄匹配的对照组直接进行比较。结合使用核磁共振氢谱（1H NMR）和靶向数据独立液相色谱-串联质谱（DI-LC-MS/MS）获取的数据，我们发现脂肪酸氧化是死于SIDS的婴儿大脑中受到干扰的关键生化途径（p = 0.0016）。此外，我们还确定了一种潜在的中枢生物标志物，其曲线下面积（AUC，95%置信区间）= 0.933（0.845 - 1.000），在区分对照组和SIDS组大脑方面具有较高的灵敏度（0.933）和特异性（0.875）值。这是首次报道使用靶向代谢组学研究死于SIDS的婴儿脑内延髓的研究。我们已经确定了与该疾病相关的途径和用于早期筛查/诊断的中枢生物标志物。
