Villaseñor Alma, Kinross James M, Li Jia V, Penney Nicholas, Barton Richard H, Nicholson Jeremy K, Darzi Ara, Barbas Coral, Holmes Elaine
Section of Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London , Sir Alexander Fleming Building, Exhibition Road, South Kensington, London SW7 2AZ, United Kingdom.
J Proteome Res. 2014 Dec 5;13(12):5362-75. doi: 10.1021/pr500161w. Epub 2014 Oct 8.
We have investigated the urinary and plasma metabolic phenotype of acute pancreatitis (AP) patients presenting to the emergency room at a single center London teaching hospital with acute abdominal pain using (1)H NMR spectroscopy and multivariate modeling. Patients were allocated to either the AP (n = 15) or non-AP patients group (all other causes of abdominal pain, n = 21) on the basis of the national guidelines. Patients were assessed for three clinical outcomes: (1) diagnosis of AP, (2) etiology of AP caused by alcohol consumption and cholelithiasis, and (3) AP severity based on the Glasgow score. Samples from AP patients were characterized by high levels of urinary ketone bodies, glucose, plasma choline and lipid, and relatively low levels of urinary hippurate, creatine and plasma-branched chain amino acids. AP could be reliably identified with a high degree of sensitivity and specificity (OPLS-DA model R(2) = 0.76 and Q(2)Y = 0.59) using panel of discriminatory biomarkers consisting of guanine, hippurate and creatine (urine), and valine, alanine and lipoproteins (plasma). Metabolic phenotyping was also able to distinguish between cholelithiasis and colonic inflammation among the heterogeneous non-AP group. This work has demonstrated that combinatorial biomarkers have a strong diagnostic and prognostic potential in AP with relevance to clinical decision making in the emergency unit.
我们利用氢核磁共振波谱法和多变量建模,对伦敦一家单中心教学医院急诊室中因急性腹痛就诊的急性胰腺炎(AP)患者的尿液和血浆代谢表型进行了研究。根据国家指南,将患者分为AP组(n = 15)或非AP患者组(所有其他腹痛原因,n = 21)。对患者评估了三项临床结果:(1)AP的诊断,(2)由饮酒和胆石症引起的AP病因,以及(3)基于格拉斯哥评分的AP严重程度。AP患者的样本特征为尿酮体、葡萄糖、血浆胆碱和脂质水平较高,而尿马尿酸盐、肌酸和血浆支链氨基酸水平相对较低。使用由鸟嘌呤、马尿酸盐和肌酸(尿液)以及缬氨酸、丙氨酸和脂蛋白(血浆)组成的一组鉴别生物标志物,能够以高度的敏感性和特异性可靠地识别AP(OPLS-DA模型R(2) = 0.76,Q(2)Y = 0.59)。代谢表型分析还能够在异质性非AP组中区分胆石症和结肠炎症。这项工作表明,组合生物标志物在AP中具有强大的诊断和预后潜力,与急诊科的临床决策相关。