Seta N, Gayno S, Jezequel-Cuer M, Toueg M L, Erlinger S, Durand G
Laboratoire de Biochimie A, Hôpital Xavier Bichat, Paris, France.
J Hepatol. 1997 Feb;26(2):265-71. doi: 10.1016/s0168-8278(97)80040-2.
alpha-Fetoprotein is a useful diagnostic marker in hepatocellular carcinoma, during which its serum level increases and its glycan structure is hyperfucosylated. Normally-expressed glycoproteins (alpha 1-antitrypsin and transferrin) are also hyperfucosylated in hepatocellular carcinoma. alpha-fetoprotein serum levels are also increased in conditions associated with hepatic regeneration, such as acute hepatitis. We conducted a longitudinal study of the alpha 1-6 fucosylation pattern of serum alpha-fetoprotein in ten patients with acute hepatitis and compared it to that of transferrin and alpha 1-antitrypsin.
Protein levels were measured by using immunochemical assays. Crossed affinoimmunoelectrophoresis in the presence of Lens culinaris agglutinin was performed for each protein, and the fucosylation index, corresponding to the agglutinin reactive fraction, was determined. The results were compared to those in 25 healthy donors and five newborns.
alpha-Fetoprotein was hyperfucosylated and remained stable throughout the course of the disease. In contrast, serum transferrin and alpha 1-antitrypsin gradually became hyperfucosylated during the course of acute hepatitis. The transferrin and alpha 1-antitrypsin fucosylation indexes correlated with each other, but not with the alpha-fetoprotein fucosylation index. No correlation was found between alpha-fetoprotein, alpha 1-antitrypsin and transferrin fucosylation indexes and the corresponding glycoprotein serum levels.
Hyperfucosylation of alpha-fetoprotein is not specific to hepatocellular carcinoma. Increased alpha 1-6 fucosylation should not be considered solely as a tumour marker, but might also reflect cell proliferation. The study of alpha 1-6 hyperfucosylation process of normally-expressed glycoproteins awaits further investigation, to test its usefulness as a new marker of liver regeneration during the follow-up of acute hepatitis.
甲胎蛋白是肝细胞癌的一种有用诊断标志物,在此期间其血清水平升高且其聚糖结构高度岩藻糖基化。正常表达的糖蛋白(α1-抗胰蛋白酶和转铁蛋白)在肝细胞癌中也会高度岩藻糖基化。在与肝再生相关的情况下,如急性肝炎,甲胎蛋白血清水平也会升高。我们对10例急性肝炎患者血清甲胎蛋白的α1-6岩藻糖基化模式进行了纵向研究,并将其与转铁蛋白和α1-抗胰蛋白酶的模式进行比较。
使用免疫化学分析法测量蛋白质水平。对每种蛋白质进行在菜豆凝集素存在下的交叉亲和免疫电泳,并测定与凝集素反应部分相对应的岩藻糖基化指数。将结果与25名健康供体和5名新生儿的结果进行比较。
甲胎蛋白高度岩藻糖基化且在疾病过程中保持稳定。相比之下,血清转铁蛋白和α1-抗胰蛋白酶在急性肝炎过程中逐渐变得高度岩藻糖基化。转铁蛋白和α1-抗胰蛋白酶岩藻糖基化指数相互相关,但与甲胎蛋白岩藻糖基化指数不相关。未发现甲胎蛋白、α1-抗胰蛋白酶和转铁蛋白岩藻糖基化指数与相应糖蛋白血清水平之间存在相关性。
甲胎蛋白的高度岩藻糖基化并非肝细胞癌所特有。α1-6岩藻糖基化增加不应仅被视为肿瘤标志物,还可能反映细胞增殖。对正常表达糖蛋白的α1-6高度岩藻糖基化过程的研究有待进一步调查,以测试其作为急性肝炎随访期间肝再生新标志物的有用性。