CA-S27: A novel Lewis a associated carbohydrate epitope is diagnostic and prognostic for cholangiocarcinoma
CA-S27: A novel Lewis a associated carbohydrate epitope is diagnostic and prognostic for cholangiocarcinoma
复制标题
DOI：
10.1111/cas.12222
复制
发表时间：
2013-10-01
期刊：
影响因子：
5.7
通讯作者：
Wongkham, Sopit
中科院分区：
文献类型：
--
作者：
Silsirivanit, Atit;Araki, Norie;Wongkham, Sopit
早期和特异性诊断是胆管癌（CCA）治疗的关键。本研究以混合的CCA组织提取物为免疫原，建立碳水化合物抗原- s27 （CA-S27）单克隆抗体（mAb）。CA-S27-mAb识别的表位是MUC5AC粘蛋白的一个新的Lewis-a （Le(a)）相关修饰。成功建立了大豆凝集素/CA-S27- mab夹心ELISA检测血清中CA-S27的方法。CA-S27在CCA患者血清中检测到高水平的CA-S27，可将CCA患者与胃肠道肿瘤、肝癌、肝胆良性疾病及健康人进行区分，敏感性高（87.5%），阴性预测值高（90.4%）。肿瘤切除后血清CA-S27水平显著降低，提示CA-S27为肿瘤来源。无论血清MUC5AC水平如何，高血清CA-S27患者的生存期明显短于低血清CA-S27患者。focusyltransferase-III （FUT3）被证明是CA-S27表达的调节因子。用siRNA-FUT3抑制CA-S27表达或用CA-S27 mAb中和CA-S27可显著降低体外CCA细胞的生长、粘附、侵袭和迁移能力。总之，我们证明了血清CA-S27，一种新的碳水化合物抗原，有潜力作为CCA患者的诊断和预后指标。CA-S27参与促进CCA细胞的生长、粘附、迁移和侵袭。
Early and specific diagnosis is critical for treatment of cholangiocarcinoma (CCA). In this study, a carbohydrate antigen-S27 (CA-S27) monoclonal antibody (mAb) was established using pooled CCA tissue-extract as immunogen. The epitope recognized by CA-S27-mAb was a new Lewis-a (Le(a)) associated modification of MUC5AC mucin. A Soybean agglutinin/CA-S27-mAb sandwich ELISA to determine CA-S27 in serum was successfully developed. High level of CA-S27 was detected in serum of CCA patients and could differentiate CCA patients from those of gastro-intestinal cancers, hepatomas, benign hepatobiliary diseases and healthy subjects with high sensitivity (87.5%) and high negative predictive value (90.4%). The level of serum CA-S27 was dramatically reduced after tumor removal, indicating tumor origin of CA-S27. Patients with high serum CA-S27 had significantly shorter survivals than those with low serum CA-S27 regardless of serum MUC5AC levels. Fucosyltransferase-III (FUT3) was shown to be a regulator of CA-S27 expression. Suppression of CA-S27 expression with siRNA-FUT3 or neutralization with CA-S27 mAb significantly reduced growth, adhesion, invasion and migration potentials of CCA cells in vitro. In summary, we demonstrate that serum CA-S27, a novel carbohydrate antigen, has potential as diagnostic and prognostic markers for CCA patients. CA-S27 involves in promoting cell growth, adhesion, migration and invasion of CCA cells.