Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and cancer patients: implications for a biomarker of hepatocellular carcinoma.
Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and cancer patients: implications for a biomarker of hepatocellular carcinoma.
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DOI：
10.1371/journal.pone.0012419
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发表时间：
2010-08-25
期刊：
影响因子：
3.7
通讯作者：
Mehta A
中科院分区：
文献类型：
--
作者：
Comunale MA;Rodemich-Betesh L;Hafner J;Wang M;Norton P;Di Bisceglie AM;Block T;Mehta A
我们先前报道了随着肝癌的发展，蛋白质连接的岩藻糖基化水平增加，并鉴定了许多含有改变的聚糖结构的蛋白质。一种这样的蛋白质是α-1-抗胰蛋白酶（A1 AT）。为了推进这些研究，我们对A1 AT的五种主要亚型进行了N-连接聚糖分析，并完成了对健康对照、丙型肝炎（HCV）诱导的肝硬化患者和诊断为肝细胞癌（HCC）的HCV感染患者中A1 AT糖基化的全面研究。肝硬化和肝癌患者的含三触角聚糖外臂（α-1，3）岩藻糖基化水平升高。仅在癌症患者的A1 AT上观察到核心（α-1，6）岩藻糖基化增加。我们使用Aleuria Aurantia凝集素（AAL）对400多名肝病患者的核心和外臂岩藻糖基化进行了凝集素荧光团连接免疫吸附试验。AAL反应性A1 AT能够检测HCC，灵敏度为70%，特异性为86%，高于目前HCC标志物甲胎蛋白的检测结果。对假阳性进行了糖基化分析;结果表明，这些患者的外臂岩藻糖基化增加，但核心岩藻糖基化没有增加，表明核心岩藻糖基化具有癌症特异性。该报告详细描述了A1 AT糖基化从肝硬化到癌症的逐步变化，并将A1 AT的核心岩藻糖基化鉴定为HCC特异性修饰。
We previously reported increased levels of protein-linked fucosylation with the development of liver cancer and identified many of the proteins containing the altered glycan structures. One such protein is alpha-1-antitrypsin (A1AT). To advance these studies, we performed N-linked glycan analysis on the five major isoforms of A1AT and completed a comprehensive study of the glycosylation of A1AT found in healthy controls, patients with hepatitis C- (HCV) induced liver cirrhosis, and in patients infected with HCV with a diagnosis of hepatocellular carcinoma (HCC). Patients with liver cirrhosis and liver cancer had increased levels of triantennary glycan-containing outer arm (α-1,3) fucosylation. Increases in core (α-1,6) fucosylation were observed only on A1AT from patients with cancer. We performed a lectin fluorophore-linked immunosorbent assay using Aleuria Aurantia lectin (AAL), specific for core and outer arm fucosylation in over 400 patients with liver disease. AAL-reactive A1AT was able to detect HCC with a sensitivity of 70% and a specificity of 86%, which was greater than that observed with the current marker of HCC, alpha-fetoprotein. Glycosylation analysis of the false positives was performed; results indicated that these patients had increases in outer arm fucosylation but not in core fucosylation, suggesting that core fucosylation is cancer specific. This report details the stepwise change in the glycosylation of A1AT with the progression from liver cirrhosis to cancer and identifies core fucosylation on A1AT as an HCC specific modification.
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影响因子：
4.8
作者：
Nakagawa, Tsutomu;Uozumi, Naofumi;Miyoshi, Eiji
通讯作者：
Miyoshi, Eiji
影响因子：
13.5
作者：
Liu, Xue-En;Desmyter, Liesbeth;Chen, Cuiying
通讯作者：
Chen, Cuiying
DOI：
10.1046/j.1440-1746.1999.01882.x
发表时间：
1999-05-01
影响因子：
4.1
作者：
Naitoh, A;Aoyagi, Y;Asakura, H
通讯作者：
Asakura, H
影响因子：
2.8
作者：
BROOKS, KP;IAMMARINO, RM
通讯作者：
IAMMARINO, RM
影响因子：
105.7
作者：
RUOSLAHTI, E;SALASPURO, M;SEPPALA, M
通讯作者：
SEPPALA, M