Inata Junya, Hattori Noboru, Yokoyama Akihito, Ohshimo Shinichiro, Doi Mihoko, Ishikawa Nobuhisa, Hamada Hironobu, Kohno Nobuoki
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Int J Cancer. 2007 Jun 15;120(12):2643-9. doi: 10.1002/ijc.22613.
MUC1 mucin is frequently observed in adenocarcinomas, and its association with metastasis has been postulated through the interaction between sialyl Lewis oligosaccharides present on this glycoprotein and selectins. Levels of soluble MUC1 recognized by anti-KL-6 monoclonal antibody were also frequently elevated in the sera of lung adenocarcinoma patients. The aim of this study was to demonstrate the presence of KL-6/MUC1 carrying sialyl Lewis(a) oligosaccharide, designated as SLAK, and subsequently evaluate the clinical significance of circulating SLAK in patients with lung adenocarcinoma. We developed a sandwich ELISA system using anti-sialyl Lewis(a) and anti-KL-6 antibodies to detect SLAK, and also measured circulating SLAK levels in 97 healthy controls and 103 patients with lung adenocarcinoma. Circulating SLAK levels were measured in the sera taken before treatment and then were evaluated to clarify whether such levels were related to the clinical outcomes. Levels of circulating SLAK were significantly higher in lung adenocarcinoma patients than in healthy subjects, and a higher serum SLAK level was correlated with the presence of distant metastasis. The overall survival rate for patients with high serum SLAK levels was significantly poorer than that of patients with low serum SLAK levels. The survival analysis restricted to the patients with distant metastasis also showed the same trend. In a multivariate survival analysis in lung adenocarcinoma patients, a high serum SLAK level was indicated as an independent prognostic factor. In conclusion, the circulating SLAK level at diagnosis is useful for predicting a poor prognosis in patients with lung adenocarcinoma.
MUC1粘蛋白在腺癌中经常被观察到，并且通过该糖蛋白上存在的唾液酸化路易斯寡糖与选择素之间的相互作用，推测其与转移有关。抗KL-6单克隆抗体识别的可溶性MUC1水平在肺腺癌患者血清中也经常升高。本研究的目的是证明携带唾液酸化路易斯(a)寡糖的KL-6/MUC1（命名为SLAK）的存在，随后评估循环SLAK在肺腺癌患者中的临床意义。我们开发了一种使用抗唾液酸化路易斯(a)和抗KL-6抗体的夹心ELISA系统来检测SLAK，并测量了97名健康对照者和103名肺腺癌患者的循环SLAK水平。在治疗前采集的血清中测量循环SLAK水平，然后评估这些水平是否与临床结果相关。肺腺癌患者的循环SLAK水平显著高于健康受试者，血清SLAK水平较高与远处转移的存在相关。血清SLAK水平高的患者的总生存率显著低于血清SLAK水平低的患者。仅限于远处转移患者的生存分析也显示出相同的趋势。在肺腺癌患者多因素生存分析中，高血清SLAK水平被表明是一个独立的预后因素。总之，诊断时的循环SLAK水平有助于预测肺腺癌患者的不良预后。
