Atit Silsirivanit1, Atsushi Matsuda2, Atsushi Kuno3, Chikayuki Tsuruno4, Yuta Uenoyama4, Wunchana Seubwai5, Kiyohiko Angata3, Karuntarat Teeravirote6, Chaisiri Wongkham6, Norie Araki7, Youichi Takahama4, Sopit Wongkham6, Hisashi Narimatsu8. 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.
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.
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.