Zhou Kejun, Xie Guoxiang, Wang Jun, Zhao Aihua, Liu Jiajian, Su Mingming, Ni Yan, Zhou Ying, Pan Weihua, Che Yanran, Zhang Ting, Xiao Yongtao, Wang Yang, Wen Jie, Jia Wei, Cai Wei
†Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University (SJTU), 1665 Kongjiang Road, Shanghai 200092, China.
‡Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, 1665 Kongjiang Road, Shanghai 200092, China.
J Proteome Res. 2015 Jun 5;14(6):2569-74. doi: 10.1021/acs.jproteome.5b00125. Epub 2015 Apr 27.
Biliary atresia (BA) is a rare neonatal cholestatic disorder caused by obstruction of extra- and intra-hepatic bile ducts. If untreated, progressive liver cirrhosis will lead to death within 2 years. Early diagnosis and operation improve the outcome significantly. Infants with neonatal hepatitis syndrome (NHS) present similar symptoms, confounding the early diagnosis of BA. The lack of noninvasive diagnostic methods to differentiate BA from NHS greatly delays the surgery of BA infants, thus deteriorating the outcome. Here we performed a metabolomics study in plasma of BA, NHS, and healthy infants using gas chromatography-time-of-flight mass spectrometry. Scores plots of orthogonal partial least-squares discriminant analysis clearly separated BA from NHS and healthy infants. Eighteen metabolites were found to be differentially expressed between BA and NHS, among which seven (l-glutamic acid, l-ornithine, l-isoleucine, l-lysine, l-valine, l-tryptophan, and l-serine) were amino acids. The altered amino acids were quantitatively verified using ultraperformance liquid chromatography-tandem mass spectrometry. Ingenuity pathway analysis revealed the network of "Cellular Function and Maintenance, Hepatic System Development and Function, Neurological Disease" was altered most significantly. This study suggests that plasma metabolic profiling has great potential in differentiating BA from NHS, and amino acid metabolism is significantly different between the two diseases.
胆道闭锁（BA）是一种罕见的新生儿胆汁淤积性疾病，由肝内外胆管阻塞引起。若不治疗，进行性肝硬化将导致患儿在2年内死亡。早期诊断和手术可显著改善预后。新生儿肝炎综合征（NHS）患儿表现出相似症状，这使得BA的早期诊断变得困难。缺乏区分BA与NHS的非侵入性诊断方法极大地延迟了BA患儿的手术，从而使预后恶化。在此，我们使用气相色谱-飞行时间质谱对BA、NHS和健康婴儿的血浆进行了代谢组学研究。正交偏最小二乘判别分析的得分图清晰地将BA与NHS及健康婴儿区分开来。发现18种代谢物在BA和NHS之间存在差异表达，其中7种（L-谷氨酸、L-鸟氨酸、L-异亮氨酸、L-赖氨酸、L-缬氨酸、L-色氨酸和L-丝氨酸）为氨基酸。使用超高效液相色谱-串联质谱对这些变化的氨基酸进行了定量验证。 Ingenuity通路分析显示，“细胞功能与维持、肝脏系统发育与功能、神经疾病”网络的改变最为显著。本研究表明，血浆代谢谱在区分BA与NHS方面具有巨大潜力，且两种疾病之间氨基酸代谢存在显著差异。
