Multi-serum glycobiomarkers improves the diagnosis and prognostic prediction of cholangiocarcinoma

Atit Silsirivanit; Atsushi Matsuda; Atsushi Kuno; Chikayuki Tsuruno; Yuta Uenoyama; Wunchana Seubwai; Kiyohiko Angata; Karuntarat Teeravirote; Chaisiri Wongkham; Norie Araki; Youichi Takahama; Sopit Wongkham; Hisashi Narimatsu

doi:10.1016/j.cca.2020.07.017

Multi-serum glycobiomarkers improves the diagnosis and prognostic prediction of cholangiocarcinoma

Clin Chim Acta. 2020 Nov:510:142-149. doi: 10.1016/j.cca.2020.07.017. Epub 2020 Jul 11.

Authors

Affiliations

¹ Department of Biochemistry, and Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: atitsil@kku.ac.th.
² Department of Biochemistry, School of Medicine, Keio University, Tokyo 160-8582, Japan.
³ Molecular and Cellular Glycoproteomics Research Group, Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Ibaraki 305-8565, Japan.
⁴ Sysmex Corporation, Kobe 651-2271, Japan.
⁵ Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand; Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
⁶ Department of Biochemistry, and Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand.
⁷ Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
⁸ Molecular and Cellular Glycoproteomics Research Group, Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Ibaraki 305-8565, Japan. Electronic address: h.narimatsu@aist.go.jp.

PMID: 32659223
DOI: 10.1016/j.cca.2020.07.017

Abstract

Background: Aberrant glycosylation has been reported to play important roles in progression of cholangiocarcinoma (CCA) and hence the aberrant expressed glycans are beneficial markers for diagnosis and prognostic prediction of CCA.

Methods: Five CCA-associated glycobiomarkers-carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen-S27 (CA-S27), CCA-associated carbohydrate antigen (CCA-CA), WFA-positive MUC1 (WFA⁺-MUC1), and WFA-positive M2BP (WFA⁺-M2BP), in the sera from CCA patients (N = 138) were determined in comparison with non-CCA control subjects (N = 246).

Results: Receiver operating characteristic analysis suggested the significance of each glycobiomarker in discriminating CCA from non-CCA with area under curve of 0.580-0.777. High levels of CA19-9, CCA-CA, CA-S27, or WFA⁺-MUC1 were associated with poor prognosis and poor survival of CCA patients. Combination of these glycobiomarkers and graded as a GlycoBiomarker (GB)-score could increase the power of the tests in diagnosis than an individual marker with 81% of sensitivity, specificity and accuracy.

Conclusions: According to the GB-score, these glycobiomarkers not only increased diagnostic power but also discriminated survival of patients indicating the diagnostic and prognostic values of GB-score.

Keywords: Bile duct; Cancer; Carbohydrate; Glycan; Lectin; Liver; Marker; Serum.

MeSH terms

Bile Duct Neoplasms* / diagnosis
Bile Ducts, Intrahepatic
Biomarkers, Tumor
CA-19-9 Antigen
Cholangiocarcinoma* / diagnosis
Humans
Prognosis

Substances

Biomarkers, Tumor
CA-19-9 Antigen