Wisteria floribunda Agglutinin-Positive Mucin 1 Is a Sensitive Biliary Marker for Human Cholangiocarcinoma

Wisteria floribunda Agglutinin-Positive Mucin 1 Is a Sensitive Biliary Marker for Human Cholangiocarcinoma
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DOI:
10.1002/hep.23654
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发表时间:
2010-07-01
期刊:
影响因子:
13.5
通讯作者:
Narimatsu, Hisashi
Narimatsu, Hisashi
中科院分区:
医学1区
文献类型:
--
作者:
Matsuda, Atsushi;Kuno, Atsushi;Narimatsu, Hisashi

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胆管癌(CC)是一种侵袭性恶性肿瘤,目前还没有有效的标志物用于早期和精确诊断。因此,本研究的目的是鉴定一种高性能的诊断标记物,特别关注糖蛋白的糖改变。在研究过程中,我们发现紫藤凝集素(WFA)是鉴别肝内胆管癌(ICC)病变与正常胆管上皮(BDE)病变的最佳探针(P < 0.0001)。随后的组织化学研究证实了165个组织标本的icc特异性WFA染色。另一方面,通过双染色实验表明,WFA染色与先前建立的my1 . 1e12抗唾液化粘蛋白1 (MUC1)的染色密切相关。此外,通过对CC患者wfa捕获的胆汁样本进行western blotting,可以证实MUC1的糖改变。因此,我们试图构建一种酶联免疫吸附检测系统,以更方便的CC诊断,其中wfa包被板,特异性单克隆抗体MY.1E12,以及CC胆汁标本,包括ICC (n = 30)和良性疾病(n = 38)。因此,CC与良性疾病有明显的区别,其统计学评分(敏感性= 90.0%,特异性= 76.3%,曲线下面积= 0.85)。特别值得一提的是,所获得的灵敏度是迄今为止报告的灵敏度中最高的。结论:我们的方法聚焦于一种特殊糖蛋白的显著糖改变,产生了一种新的CC诊断系统,具有令人满意的临床评分。(肝脏病学52:174 2010;182)
Cholangiocarcinoma (CC) is an aggressive malignant tumor for which useful markers are not presently available for early and precise diagnosis. The aim of this study was therefore to identify a high-performance diagnostic marker with a special focus on glyco-alteration of glycoproteins. In the course of study, we found that Wisteria floribunda agglutinin (WFA) is the best probe to differentiate intrahepatic cholangiocarcinoma (ICC) lesions from normal bile duct epithelia (BDE) (P < 0.0001). The subsequent histochemical study confirmed ICC-specific WFA staining on 165 tissue specimens. On the other hand, the WFA staining was shown to be closely associated with that of MY.1E12 established previously against sialylated mucin 1 (MUC1) by double-staining experiments. Moreover, glyco-alteration of MUC1 could be verified by western blotting of WFA-captured bile samples from patients with CC patients. Thus, we attempted to construct an enzyme-linked immunosorbent assay system for more convenient CC diagnosis, where WFA-coated plates, the specific monoclonal antibody MY.1E12, and the bile specimens from CC including ICC (n = 30) and benign diseases (n = 38) were combined. As a result, CC was clearly distinguished from benign diseases with statistical scores (sensitivity = 90.0%, specificity = 76.3%, and area under the curve = 0.85). As a particular note, the obtained sensitivity is the highest score among those having been so far reported. Conclusion: Our approach focusing significant glyco-alteration of a particular glycoprotein yielded a novel diagnostic system for CC with satisfactory clinical scores. (HEPATOLOGY 2010;52:174-182)