通过二维差异凝胶电泳（2-D DIGE）鉴定丙型肝炎病毒（HCV）感染的肝硬化患者血浆中肝细胞癌的候选生物标志物。
Identification of candidate biomarkers for hepatocellular carcinoma in plasma of HCV-infected cirrhotic patients by 2-D DIGE.
作者信息
Ferrín Gustavo, Ranchal Isidora, Llamoza Camilo, Rodríguez-Perálvarez Manuel L, Romero-Ruiz Antonio, Aguilar-Melero Patricia, López-Cillero Pedro, Briceño Javier, Muntané Jordi, Montero-Álvarez José L, De la Mata Manuel
机构信息
Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain; Networked Biomedical Research Center, Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain.
出版信息
Liver Int. 2014 Mar;34(3):438-46. doi: 10.1111/liv.12277. Epub 2013 Aug 15.
BACKGROUND
The current methods available for screening and detecting hepatocellular carcinoma (HCC) have insufficient sensitivity and specificity, and only a low percentage of diagnosis of small tumours is based on these assays. Because HCC is usually asymptomatic at potentially curative stages, identification of biomarkers for the early detection of HCC is essential to improve patient survival.
AIM
The aim of this study was to identify candidate markers for HCC development in the plasma from hepatitis C virus (HCV)-infected cirrhotic patients.
METHODS
We compared protein expression profiles of plasma samples from HCV-infected cirrhotic patients with and without HCC, using two-dimensional fluorescence difference gel electrophoresis (2-D DIGE) coupled with MALDI-TOF/TOF mass spectrometry. The 2-D DIGE results were analysed statistically using Decyder™ software, and verified by western blot and enzyme-linked immunosorbent assay (ELISA).
RESULTS
In the plasma of HCV-infected HCC patients, we observed decreased expression of complement component 9, ficolin-3 (FCN3), serum amyloid P component (SAP), fibrinogen-gamma and immunoglobulin gamma-1 chain, and increased expression of vitronectin (VTN) and galectin-3 binding protein (G3BP) by DIGE analysis. ELISA confirmed DIGE results for VTN and G3BP but not for SAP or FCN3 in a larger patient population.
CONCLUSIONS
The proteins VTN and SAP are candidate biomarkers for HCC development in HCV-infected cirrhotic patients.
背景
目前用于筛查和检测肝细胞癌（HCC）的方法灵敏度和特异性不足，基于这些检测方法诊断出的小肿瘤比例较低。由于HCC在潜在可治愈阶段通常无症状，因此鉴定用于早期检测HCC的生物标志物对于提高患者生存率至关重要。
目的
本研究旨在鉴定丙型肝炎病毒（HCV）感染的肝硬化患者血浆中HCC发生的候选标志物。
方法
我们使用二维荧光差异凝胶电泳（2-D DIGE）结合基质辅助激光解吸电离飞行时间串联质谱（MALDI-TOF/TOF），比较了有和没有HCC的HCV感染肝硬化患者血浆样本的蛋白质表达谱。使用Decyder™软件对2-D DIGE结果进行统计分析，并通过蛋白质印迹和酶联免疫吸附测定（ELISA）进行验证。
结果
通过DIGE分析，我们观察到HCV感染的HCC患者血浆中补体成分9、纤维胶凝蛋白-3（FCN3）、血清淀粉样蛋白P成分（SAP）、纤维蛋白原γ和免疫球蛋白γ-1链的表达降低，而玻连蛋白（VTN）和半乳糖凝集素-3结合蛋白（G3BP）的表达增加。ELISA在更大的患者群体中证实了VTN和G3BP的DIGE结果，但未证实SAP或FCN3的结果。
结论
VTN和SAP蛋白是HCV感染的肝硬化患者HCC发生的候选生物标志物。
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