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Development of new pancreatic cancer marker by using Lectin Microarray

Research Project

Project/Area Number 19K18132
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionKeio University

Principal Investigator

Nakano Yutaka  慶應義塾大学, 医学部(信濃町), 助教 (70770832)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords膵癌 / レクチン / バイオマーカー / エクソソーム / マイクロアレイ / 糖鎖 / リキッドバイオプシー / レクチンアレイ / 糖鎖解析
Outline of Research at the Start

本研究では膵癌患者の血液を用いて、血液中を安定して循環しているエクソソーム表面上の癌化の過程で変化する糖鎖構造を識別するレクチンを、レクチンマイクロアレイを用いた比較糖鎖プロファイリングによって同定する。そのレクチンと結合する糖鎖からグリコプロテオミクス解析にて膵癌に特異的に発現している糖蛋白質を同定し、レクチンと抗体による疾患特異的血中エクソソームを同時検出することで、早期診断や治療効果判定を可能とするバイオマーカーを開発する。

Outline of Final Research Achievements

We analyzed the dierential glycomic profiling of extracellular vesicles (EVs) derived from serum using lectin microarray. The glyco-candidates of PC-specific EVs were quantified using a high-sensitive exosome-counting system, ExoCounter. An absolute quantification system for altered glycan-containing EVs elevated in PC serum was established. EVs recognized by O-glycan-binding lectins ABA or ACA were identified as candidate markers by lectin microarray. Quantitative analyses using ExoCounter revealed that the ABA- or ACA-positive EVs were significantly increased in the culture of PC cell lines or in the serum of PC patients including carbohydrate antigen 19-9 negative patients with high area under curve values. Histological examination confirmed that the tumors stained with ABA/ACA. These specific EVs with O-glycans recognized by ABA/ACA are elevated in PC sera and can act as potential biomarkers in a liquid biopsy for PC patients screening.

Academic Significance and Societal Importance of the Research Achievements

これまで膵癌由来エクソソーム表面の糖鎖解析やレクチンを用いたエクソソーム数の測定については報告がなく、本研究が初めての報告である。さらに本研究方法は他疾患に応用可能であるため、癌研究領域のみならず様々な分野でのバイオマーカー探索にインパクトを与えたと考える。そして今回確立したエクソソーム数計測系はわずか12.5μLの検体から合計3時間半で解析可能である点で実用的である。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (2 results)

All 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] O-Glycan-Altered Extracellular Vesicles: A Specific Serum Marker Elevated in Pancreatic Cancer2020

    • Author(s)
      Yokose, T., et al., Koshiba, S., et al., Kitagawa, Y.(合計32名、本研究者は26番目)
    • Journal Title

      Cancers

      Volume: 12 Issue: 9 Pages: 2469-2469

    • DOI

      10.3390/cancers12092469

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Patent(Industrial Property Rights)] 膵臓がん検出方法及び膵臓がん検出キット2020

    • Inventor(s)
      糸長誠小野雅之横瀬崇寛松田厚志加部泰明松田祐子平井美和北郷実
    • Industrial Property Rights Holder
      糸長誠小野雅之横瀬崇寛松田厚志加部泰明松田祐子平井美和北郷実
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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