Open AccessCA ‐S27: A novel Lewis a associated carbohydrate epitope is diagnostic and prognostic for cholangiocarcinoma
Author(s) -
Silsirivanit Atit,
Araki Norie,
Wongkham Chaisiri,
Vaeteewoottacharn Kulthida,
Pairojkul Chawalit,
Kuwahara Kazuhiko,
Narimatsu Yoshiki,
Sawaki Hiromichi,
Narimatsu Hisashi,
Okada Seiji,
Sakaguchi Nobuo,
Wongkham Sopit
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12222
Subject(s) - epitope , biology , monoclonal antibody , antigen , immunogen , biochemistry , chemistry , immunology , antibody
Early and specific diagnosis is critical for treatment of cholangiocarcinoma ( CCA ). In this study, a carbohydrate antigen‐S27 ( CA ‐ S 27) monoclonal antibody (m A b) was established using pooled CCA tissue‐extract as immunogen. The epitope recognized by CA ‐ S 27‐m A b was a new L ewis‐a ( L e a ) associated modification of MUC 5 AC mucin. A S oybean agglutinin/ CA ‐S27‐m A b sandwich ELISA to determine CA ‐ S 27 in serum was successfully developed. High level of CA ‐ S 27 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 ‐ S 27 was dramatically reduced after tumor removal, indicating tumor origin of CA ‐ S 27. Patients with high serum CA ‐ S 27 had significantly shorter survivals than those with low serum CA ‐ S 27 regardless of serum MUC 5AC levels. Fucosyltransferase‐III ( FUT 3) was shown to be a regulator of CA ‐ S 27 expression. Suppression of CA ‐ S 27 expression with si RNA ‐ FUT 3 or neutralization with CA ‐ S 27 m A b significantly reduced growth, adhesion, invasion and migration potentials of CCA cells in vitro . In summary, we demonstrate that serum CA ‐ S 27, a novel carbohydrate antigen, has potential as diagnostic and prognostic markers for CCA patients. CA ‐ S 27 involves in promoting cell growth, adhesion, migration and invasion of CCA cells.