PMID- 23809433 OWN - NLM STAT- MEDLINE DCOM- 20131126 LR - 20211021 IS - 1349-7006 (Electronic) IS - 1347-9032 (Print) IS - 1347-9032 (Linking) VI - 104 IP - 10 DP - 2013 Oct TI - CA-S27: a novel Lewis a associated carbohydrate epitope is diagnostic and prognostic for cholangiocarcinoma. PG - 1278-84 LID - 10.1111/cas.12222 [doi] AB - 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. CI - (c) 2013 Japanese Cancer Association. FAU - Silsirivanit, Atit AU - Silsirivanit A AD - Department of Biochemistry, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Araki, Norie AU - Araki N FAU - Wongkham, Chaisiri AU - Wongkham C FAU - Vaeteewoottacharn, Kulthida AU - Vaeteewoottacharn K FAU - Pairojkul, Chawalit AU - Pairojkul C FAU - Kuwahara, Kazuhiko AU - Kuwahara K FAU - Narimatsu, Yoshiki AU - Narimatsu Y FAU - Sawaki, Hiromichi AU - Sawaki H FAU - Narimatsu, Hisashi AU - Narimatsu H FAU - Okada, Seiji AU - Okada S FAU - Sakaguchi, Nobuo AU - Sakaguchi N FAU - Wongkham, Sopit AU - Wongkham S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130806 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Neoplasm) RN - 0 (Antigens, Neoplasm) RN - 0 (Epitopes) RN - 0 (Lewis Blood Group Antigens) RN - 0 (Lewis a oligosaccharide) RN - 0 (MUC5AC protein, human) RN - 0 (Mucin 5AC) RN - 0 (Neoplasm Proteins) RN - 0 (Oligosaccharides) RN - EC 2.4.1.- (Fucosyltransferases) RN - EC 2.4.1.65 (3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase) SB - IM MH - Aged MH - Amino Acid Sequence MH - Antibodies, Monoclonal/immunology MH - Antibodies, Neoplasm/immunology MH - Antigens, Neoplasm/blood/*immunology MH - Bile Duct Neoplasms/chemistry/*diagnosis/immunology MH - Bile Ducts, Intrahepatic/chemistry/*immunology MH - Cell Adhesion/physiology MH - Cholangiocarcinoma/chemistry/*diagnosis/immunology MH - Diagnosis, Differential MH - Digestive System Neoplasms/diagnosis MH - Epithelial Cells/chemistry/immunology MH - Epitopes/blood/*immunology MH - Female MH - Fucosyltransferases/antagonists & inhibitors/physiology MH - Humans MH - Lewis Blood Group Antigens MH - Liver Diseases/diagnosis MH - Male MH - Middle Aged MH - Molecular Sequence Data MH - Mucin 5AC/blood/chemistry/*immunology MH - Neoplasm Invasiveness MH - Neoplasm Proteins/antagonists & inhibitors/physiology MH - Oligosaccharides/*immunology MH - Predictive Value of Tests MH - RNA Interference MH - Sensitivity and Specificity MH - Survival Analysis MH - Tumor Cells, Cultured/metabolism/pathology PMC - PMC7656540 EDAT- 2013/07/03 06:00 MHDA- 2013/12/16 06:00 PMCR- 2013/10/01 CRDT- 2013/07/02 06:00 PHST- 2013/04/03 00:00 [received] PHST- 2013/06/17 00:00 [revised] PHST- 2013/06/18 00:00 [accepted] PHST- 2013/07/02 06:00 [entrez] PHST- 2013/07/03 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] PHST- 2013/10/01 00:00 [pmc-release] AID - CAS12222 [pii] AID - 10.1111/cas.12222 [doi] PST - ppublish SO - Cancer Sci. 2013 Oct;104(10):1278-84. doi: 10.1111/cas.12222. Epub 2013 Aug 6.