The serum proteome of nonalcoholic fatty liver disease: A multimodal approach to discovery of biomarkers of nonalcoholic steatohepatitis
The serum proteome of nonalcoholic fatty liver disease: A multimodal approach to discovery of biomarkers of nonalcoholic steatohepatitis
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DOI：
10.1111/jgh.12614
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发表时间：
2014-10-01
影响因子：
4.1
通讯作者：
Dillon, John F.
中科院分区：
文献类型：
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作者：
Miller, Michael H.;Walsh, Shaun V.;Dillon, John F.
背景和目的非酒精性脂肪性肝病(NAFLD)是一种常见的疾病，在发达国家高达25%。它是一种进行性疾病，在某些情况下会导致肝硬变。目前，只有肝脏活检的组织学检查才能对这种情况进行准确的诊断和分期。这种黄金标准测试既不适合也不实用于大规模使用，因为对于像NAFLD这样常见的情况来说是必要的。本研究的目的是用两种不同的鸟枪式蛋白质组学方法描述人NAFLD的蛋白质组，将结果转化为NAFLD的潜在生物标志物。方法用两种不同的鸟枪式蛋白质组学技术(iTRAQ和Label Free)描述NAFLD的蛋白质组。结果对NAFLD蛋白质组进行了550多个蛋白质的鉴定。与正常对照组比较，非酒精性脂肪性肝炎患者外周血中载脂蛋白E、胰岛素样生长因子结合蛋白3、维生素D结合蛋白和淋巴细胞胞浆蛋白1的表达均显著上调/下调，分别为1.67倍、1.642倍、4.587倍和4.356倍。对这些蛋白的部分亚集进行酶联免疫吸附试验证实了蛋白质组学研究的有效性，并提出了可能的NAFLD新的生物标志物。结论血清标志物能够区分NAFLD的疾病分期，并能检测纤维化程度。最终，在对疑似NAFLD患者的调查中，非侵入性血清标志物可能会取代肝脏活检。
Background and AimNonalcoholic fatty liver disease (NAFLD) is a common condition affecting up to 25% of the developed world. It is a progressive disease, leading in some to the development of liver cirrhosis. Currently, accurate diagnosis and staging of this condition is only possible with histological examination of a liver biopsy. This gold standard test is neither suitable nor practical for large-scale use as is necessary for a condition as common as NAFLD. The aim of this study is to describe the proteome of human NAFLD using two distinct shotgun proteomic methods, translating the findings into potential biomarkers of NAFLD.MethodsTwo distinct shotgun proteomic techniques (iTRAQ and label free) were used to describe the proteome of NAFLD. Thereafter, candidate biomarkers were selected for validation by ELISA.ResultsOver 550 protein identifications were made in the description of the NAFLD proteome. Several proteins were found to be significantly up/downregulated in nonalcoholic steatohepatitis compared with control, including apolipoprotein E (fold ratio of 1.67), insulin-like growth factor-binding protein 3 (IGFBP3, fold ratio of 1.642), Vitamin D-binding protein (fold ratio of 4.587), and lymphocyte cytosolic protein1 (LCP1, fold ratio of 4.356). ELISA validation of a subset of these proteins confirms the validity of the proteomic studies and suggests possible new biomarkers of NAFLD.ConclusionSerum markers are able to distinguish between the stages of disease in NAFLD as well as detect the grade of fibrosis. Ultimately, noninvasive serum markers may replace liver biopsy in the investigation of patients with suspected NAFLD.