Circulating KL-6/MUC1 mucin carrying sialyl Lewisa oligosaccharide is an independent prognostic factor in patients with lung adenocarcinoma

MUCI 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 MUCI 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' 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 clarity 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. (c) 2007 Wiley-Liss, Inc.