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

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• 作者：Atsushi Matsuda ; Atsushi Kuno ; Tomomi Nakagawa ; Yuzuru Ikehara ; Tatsuro Irimura ; Masakazu Yamamoto ; Yasuni Nakanuma ; Eiji Miyoshi ; Shoji Nakamori ; Hayao Nakanishi ; Chutiwan Viwatthanasittiphong ; Petcharin Srivatanakul ; Masanao Miwa ; Junichi Shoda ; Hisashi Narimatsu
• 刊名：Analytical Chemistry
• 出版年：2015
• 出版时间：July 21, 2015
• 年：2015
• 卷：87
• 期：14
• 页码：7274-7281
• 全文大小：379K
• ISSN：1520-6882

文摘

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 渭L 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鈥揳ntibody 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.