Departments of Gastroenterology and Hepatology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
Eur J Gastroenterol Hepatol. 2010 Sep;22(9):1066-73. doi: 10.1097/MEG.0b013e328337d602.
Invasive liver biopsy is the current method for the assessment of liver fibrosis. In search of noninvasive alternatives, galectin-3-binding protein (G3BP) was introduced as a candidate-marker of hepatitis C-related fibrosis based on serum proteomics. We investigated the role of G3BP as a single-marker of significant fibrosis and cirrhosis by serology and histology and studied the effect of glycosylation on antibody-affinity in hepatitis C and alcoholic cirrhosis.
Sera and available biopsies of hepatitis C patients with various fibrosis-grades and patients with alcoholic cirrhosis were used for G3BP-measurements by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. Glycosylation-effect was analyzed by western blot. Data was analyzed in accordance to fibrosis.
G3BP-levels (mean+/-standard deviation) were increased during cirrhosis (22.7+/-10.1 microg/ml) compared to mild (11.3+/-6.4 microg/ml) and moderate fibrosis (13.4+/-8.3 microg/ml) (P<0.001; P=0.004, respectively). Receiver operator characteristic curves showed areas under the curve of 0.68, 0.75 and 0.81 for detection of significant fibrosis, severe fibrosis, and cirrhosis, respectively. Similar findings in hepatic G3BP expression were obtained, in which cirrhosis was associated with diffuse, parenchymal expression (P=0.002). The observed difference between hepatitis C and alcoholic cirrhosis (13.5+/-9.0 microg/ml) (P=0.009) could not be explained by glycosylation.
Our recent findings confirm our initial proteome results on serological and histological level as well as the role of G3BP as a marker of hepatitis C-related fibrosis, especially cirrhosis. Implication of this protein in future multi-marker study should be considered.
肝组织活检是目前评估肝纤维化的方法。为了寻找非侵入性替代方法,基于血清蛋白质组学,半乳糖凝集素-3 结合蛋白(G3BP)被引入作为丙型肝炎相关纤维化的候选标志物。我们通过血清学和组织学研究了 G3BP 作为显著纤维化和肝硬化单一标志物的作用,并研究了糖基化对丙型肝炎和酒精性肝硬化中抗体亲和力的影响。
使用丙型肝炎患者不同纤维化程度的血清和可获得的肝组织活检标本,通过酶联免疫吸附试验和免疫组织化学法分别检测 G3BP 的含量。通过 Western blot 分析糖基化的影响。根据纤维化程度对数据进行分析。
与轻度纤维化(11.3±6.4μg/ml)和中度纤维化(13.4±8.3μg/ml)相比,肝硬化(22.7±10.1μg/ml)时 G3BP 水平(平均值±标准差)升高(P<0.001;P=0.004)。受试者工作特征曲线显示,检测显著纤维化、严重纤维化和肝硬化的曲线下面积分别为 0.68、0.75 和 0.81。在肝 G3BP 表达中也得到了类似的发现,其中肝硬化与弥漫性、实质表达相关(P=0.002)。丙型肝炎和酒精性肝硬化之间(13.5±9.0μg/ml)的观察差异(P=0.009)不能用糖基化来解释。
我们最近的发现证实了我们在血清学和组织学水平上的初步蛋白质组学结果,以及 G3BP 作为丙型肝炎相关纤维化标志物,特别是肝硬化的作用。应考虑该蛋白在未来的多标志物研究中的应用。