title: Lectin Microarray-Based Sero-Biomarker Verification Targeting Aberrant O-Linked Glycosylation on Mucin 1.
abstract: Glycoform of mucin 1 (MUC1) in cancerous cells changes markedly with cell differentiation, and thus, qualitative detection and verification of the MUC1 glycosylation changes have potential diagnostic value. We have developed an ultrasensitive method to detect the changes in cholangiocarcinoma (CC), which produces MUC1, and applied it in the diagnostics development. The focused glycan analysis using 43-lectin-immobilized microarray could obtain the glycan profiles of sialylated MUC1 in 5 μL of sera. The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). Sensitive detection of qualitative alterations of sialylated MUC1 glycosylation is indispensable for the development of our glycodiagnostic test for CC.
authors.affiliation: †Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 2, 1-1-1, Umezono, Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Matsuda
authors.affiliation: †Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 2, 1-1-1, Umezono, Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kuno
authors.affiliation: †Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 2, 1-1-1, Umezono, Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: †Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 2, 1-1-1, Umezono, Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Ikehara
authors.affiliation: ‡Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421 Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Irimura
authors.affiliation: §Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: ∥Department of Human Pathology, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa 920-8641 Japan.
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.affiliation: ⊥Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
authors.affiliation: #National Hospital Organization Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka 540-0006, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Nakamori
authors.affiliation: ¶Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan.
authors.forename: Hayao
authors.initials: H
authors.lastname: Nakanishi
authors.affiliation: ●Ubon Cancer Center of Thailand, 405 Khung a-wuth Road, Ubon Ratchathani 34000, Thailand.
authors.forename: Chutiwan
authors.initials: C
authors.lastname: Viwatthanasittiphong
authors.affiliation: ▲National Cancer Institute of Thailand, 268/1 Rama VI, Ratchathewi, Bangkok 10400, Thailand.
authors.forename: Petcharin
authors.initials: P
authors.lastname: Srivatanakul
authors.affiliation: ∇Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-Cho, Nagahama, Shiga 526-0829 Japan.
authors.forename: Masanao
authors.initials: M
authors.lastname: Miwa
authors.affiliation: ⬟Field of Basic Sports Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8574, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Shoda
authors.affiliation: †Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 2, 1-1-1, Umezono, Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
mesh_terms: D018281:Cholangiocarcinoma / Q000737:chemistry*; D006031:Glycosylation; D006801:Humans; D037102:Lectins / Q000737:chemistry*; D018396:Mucin-1 / Q000097:blood* / Q000378:metabolism; D040081:Protein Array Analysis
chemical_list: D037102:Lectins; C060192:MUC1 protein, human; D018396:Mucin-1