Serum proteomic profiling in patients with drug-induced liver injury.
Serum proteomic profiling in patients with drug-induced liver injury.
复制标题
药物性肝损伤患者的血清蛋白质组学分析
DOI：
10.1111/j.1365-2036.2011.04982.x
复制
发表时间：
2012-03
影响因子：
7.6
通讯作者：
US Drug-Induced Liver Injury Network (DILIN) Research Group
中科院分区：
文献类型：
--
作者：
Bell LN;Vuppalanchi R;Watkins PB;Bonkovsky HL;Serrano J;Fontana RJ;Wang M;Rochon J;Chalasani N;US Drug-Induced Liver Injury Network (DILIN) Research Group
特异质药物性肝损伤（DILI）是一种难以预测、诊断和治疗的复杂疾病。描述DILI患者和对照组的总体血清蛋白质组。一种无标记的、基于质谱的定量蛋白质组学方法被用于探索来自74名DILI患者（在DILI发作的14天内收集）和40名对照的血清样品中的蛋白质表达。在21例DILI患者的亚组中进行了纵向分析，并提供了6个月的随访血清样本。基于肝损伤的模式、严重程度和因果关系评估的DILI患者的比较揭示了组间许多差异表达的优先级1蛋白。延胡索酰乙酰乙酸酶的表达与丙氨酸氨基转移酶的表达相关（ALT; r = 0.237; P = 0.047），天冬氨酸转氨酶（AST; r = 0.389; P = 0.001）和碱性磷酸酶（r =-0.240; P = 0.043），当比较肝细胞损伤与胆汁淤积性损伤或混合性损伤时，这是唯一具有显著差异表达的蛋白质。在纵向分析中，从DILI发作到6个月随访，53种优先级1蛋白的表达发生显著变化，几乎所有蛋白都恢复到与对照受试者相当的表达水平。当比较DILI组和对照组时，鉴定出92种具有显著差异表达的血清优先级1蛋白。模式分析揭示了作为炎症、免疫系统激活和几种肝毒性特异性途径的组分的蛋白质。载脂蛋白E表达对区分DILI患者和对照组具有最大的功效（89%正确分类; AUROC = 0.97）。该蛋白质组学分析鉴定了差异表达的蛋白质，这些蛋白质是先前与特异质药物诱导的肝损伤的发病机制有关的途径的组分。
Idiosyncratic drug-induced liver injury (DILI) is a complex disorder that is difficult to predict, diagnose and treat. To describe the global serum proteome of patients with DILI and controls. A label-free, mass spectrometry-based quantitative proteomic approach was used to explore protein expression in serum samples from 74 DILI patients (collected within 14 days of DILI onset) and 40 controls. A longitudinal analysis was conducted in a subset of 21 DILI patients with available 6-month follow-up serum samples. Comparison of DILI patients based on pattern, severity and causality assessment of liver injury revealed many differentially expressed priority 1 proteins among groups. Expression of fumarylacetoacetase was correlated with alanine aminotransferase (ALT; r = 0.237; P = 0.047), aspartate aminotransferase (AST; r = 0.389; P = 0.001) and alkaline phosphatase (r = −0.240; P = 0.043), and this was the only protein with significant differential expression when comparing patients with hepatocellular vs. cholestatic or mixed injury. In the longitudinal analysis, expression of 53 priority 1 proteins changed significantly from onset of DILI to 6-month follow-up, and nearly all proteins returned to expression levels comparable to control subjects. Ninety-two serum priority 1 proteins with significant differential expression were identified when comparing the DILI and control groups. Pattern analysis revealed proteins that are components of inflammation, immune system activation and several hepatotoxicity-specific pathways. Apolipoprotein E expression had the greatest power to differentiate DILI patients from controls (89% correct classification; AUROC = 0.97). This proteomic analysis identified differentially expressed proteins that are components of pathways previously implicated in the pathogenesis of idiosyncratic drug-induced liver injury.
登录
查看更多内容
影响因子：
4.4
作者：
Craig, Andrew;Sidaway, James;Nicholson, Jeremy
通讯作者：
Nicholson, Jeremy
DOI：
10.1152/ajpgi.00547.2007
发表时间：
2009-03-01
影响因子：
4.5
作者：
Ferre, Natalia;Martinez-Clemente, Marcos;Claria, Joan
通讯作者：
Claria, Joan
影响因子：
4.4
作者：
Higgs, Richard E.;Knierman, Michael D.;Hale, John E.
通讯作者：
Hale, John E.
影响因子：
9.3
作者：
Amacher, DE;Adler, R;Townsend, RR
通讯作者：
Townsend, RR
影响因子：
5.8
作者：
Craig, R;Beavis, RC
通讯作者：
Beavis, RC