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A novel serum carbohydrate marker on mucin 5AC†
Values for diagnostic and prognostic indicators for cholangiocarcinoma
Article first published online: 1 FEB 2011
Copyright © 2011 American Cancer Society
Volume 117, Issue 15, pages 3393–3403, 1 August 2011
How to Cite
Silsirivanit, A., Araki, N., Wongkham, C., Pairojkul, C., Narimatsu, Y., Kuwahara, K., Narimatsu, H., Wongkham, S. and Sakaguchi, N. (2011), A novel serum carbohydrate marker on mucin 5AC. Cancer, 117: 3393–3403. doi: 10.1002/cncr.25912
N. Sakaguchi is a member of the Global Centers of Excellence Program of Acquired Immunodeficiency Syndrome Research in Japan.
- Issue published online: 20 JUL 2011
- Article first published online: 1 FEB 2011
- Manuscript Revised: 7 DEC 2010
- Manuscript Accepted: 7 DEC 2010
- Manuscript Received: 23 OCT 2010
- tumor marker;
- enzyme-linked immunosorbent assay;
- carbohydrate marker;
- mucin, mucin 5AC
The incidence of cholangiocarcinoma (CCA) is increasing globally. Currently, there is no powerful marker for the diagnosis of CCA, which has led to late diagnosis and poor patient outcome. This study was designed to establish a new monoclonal antibody (MoAb) for detecting a serum marker associated with CCA.
Pooled CCA tissue extracts were immunized to germinal center associated nuclear protein (GANP)-transgenic mice. The antibody-producing hybridomas were prepared and initially screened by using an indirect enzyme-linked immunosorbent assay (ELISA). A positive clone that reacted strongly with CCA serum or tumor tissue extract and failed to react with normal human serum and liver extract was selected.
An S121 immunoglobulin M MoAb that recognized a novel glycan epitope was obtained. Immunohistochemistry of CCA tissues revealed that the MoAb reacted strongly with hyperplastic/dysplastic and neoplastic bile ducts but not with normal bile ducts. In addition, experiments demonstrated that mucin 5AC (MUC5AC) is a core glycoprotein for the S121 epitope. A sandwich ELISA using soybean agglutinin and an S121 MoAb was developed for detecting S121 reactive antigen in patient sera. The level of serum S121 from patients with CCA was reduced significantly after tumor removal, indicating the tumor origin of this antigen. The test was able to distinguish patients with CCA from healthy individuals, active Opisthorchisviverrini-infected individuals and patients with various gastrointestinal cancers, hepatoma, and benign hepatobiliary diseases with 87.63% sensitivity, 89.58% specificity, an 80.95% positive predictive value, and a 93.47% negative predictive value. Moreover, high serum S121 levels were related to a poor patient outcome.
The sugar antigen recognized by S121 MoAb is a new serum marker for the diagnosis and prognosis of CCA. Cancer 2011. © 2011 American Cancer Society.