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Anal Chem. 2015 Jul 21;87(14):7274-81. doi: 10.1021/acs.analchem.5b01329. Epub 2015 Jul 7.

Lectin Microarray-Based Sero-Biomarker Verification Targeting Aberrant O-Linked Glycosylation on Mucin 1.

Author information

1
†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.
2
‡Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421 Japan.
3
§Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan.
4
∥Department of Human Pathology, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa 920-8641 Japan.
5
⊥Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 Japan.
6
#National Hospital Organization Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka 540-0006, Japan.
7
¶Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan.
8
●Ubon Cancer Center of Thailand, 405 Khung a-wuth Road, Ubon Ratchathani 34000, Thailand.
9
▲National Cancer Institute of Thailand, 268/1 Rama VI, Ratchathewi, Bangkok 10400, Thailand.
10
∇Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-Cho, Nagahama, Shiga 526-0829 Japan.
11
⬟Field of Basic Sports Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8574, Japan.

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.

PMID:
26091356
DOI:
10.1021/acs.analchem.5b01329
[Indexed for MEDLINE]

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