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Investigation of free-glycan-based tumor markers and development of their quantification method

Research Project

Project/Area Number 22K15700
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionGifu University

Principal Investigator

Hanzawa Ken  岐阜大学, 糖鎖生命コア研究所, 研究員 (00808347)

Project Period (FY) 2022-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords糖鎖 / 遊離糖鎖 / がん / 尿 / 高速液体クロマトグラフィー / 質量分析 / 腫瘍マーカー / LC/MS / HPLC
Outline of Research at the Start

糖鎖関連腫瘍マーカーは臨床検査で広く用いられているが、それらは糖タンパク質・糖脂質として存在する。申請者らは遊離糖鎖に着目した腫瘍マーカー開発を試みており、これまでに主要な尿中遊離糖鎖解析により、がん患者において増加傾向を示す糖鎖を報告している。本研究では、尿中遊離糖鎖に関して、その伸長・分枝・修飾に着目し、微量であるがより複雑な分子の探索を行い、より特異性の高い腫瘍マーカー候補の発見を目指す。見つかったマーカー候補糖鎖は、臨床応用に向けて液体クロマトグラフィー-質量分析(LC/MS/MS)により、複数種類を迅速に定量できるように条件を検討し、多検体分析によるバリデーションを目指し進めていく。

Outline of Final Research Achievements

Urinary free-glycans of cancer patients were investigated focusing on the fractions of large molecular size, which have not been analyzed before. Glycan structures were analyzed based on detailed chromatographic fractionation and enzymatic and chemical treatments. Comparison of glycan levels between samples was performed by selective reaction monitoring of liquid chromatography/mass spectrometry (LC/MS/MS). As a result, it was found that multiply branched free-N-glycans showed an increasing trend in some cancer patients. In addition, conditions to improve the sensitivity and stability of LC/MS/MS for the multiplex measurement of glycans were investigated.

Academic Significance and Societal Importance of the Research Achievements

糖タンパク質の糖鎖は腫瘍マーカーとして利用され、研究も盛んに行われているが、遊離糖鎖に着目した研究はあまり行われていない。本研究では、遊離糖鎖と疾患との関連、およびその測定技術に関する新たな知見を提供する。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (4 results)

All 2022

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Increased levels of acidic free-N-glycans, including multi-antennary and fucosylated structures, in the urine of cancer patients2022

    • Author(s)
      Hanzawa Ken、Tanaka-Okamoto Miki、Murakami Hiroko、Suzuki Noriko、Mukai Mikio、Takahashi Hidenori、Omori Takeshi、Ikezawa Kenji、Ohkawa Kazuyoshi、Ohue Masayuki、Natsuka Shunji、Miyamoto Yasuhide
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 4 Pages: e0266927-e0266927

    • DOI

      10.1371/journal.pone.0266927

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 尿中遊離糖鎖の検出と疾患マーカーとしての可能性2022

    • Author(s)
      半澤健、岡本三紀、村上博子、中嶋和紀、宮本泰豪
    • Organizer
      第47回日本医用マススペクトル学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] 尿中酸性遊離糖鎖とそのがん患者における変化の解析2022

    • Author(s)
      半澤健、岡本三紀、村上博子、宮本泰豪
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Sialylated free-glycans in urine and their alterations in cancer2022

    • Author(s)
      Ken Hanzawa, Miki Tanaka-Okamoto, Hiroko Murakami, Yasuhide Miyamoto
    • Organizer
      Sialoglyco2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2022-04-19   Modified: 2025-01-30  

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