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Development of an early diagnosis method for esophageal cancer using liquid biopsy based on glycan-lectin reaction

Research Project

Project/Area Number 19K18078
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Ogawa Koichi  筑波大学, 医学医療系, 講師 (20733637)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords食道癌 / レクチン / リキッドバイオプシー / 糖鎖 / 3次元オルガノイド
Outline of Research at the Start

食道扁平上皮癌手術検体より3次元腫瘍オルガノイドを作成し、食道癌に特異的に発現している糖鎖-レクチンの組み合わせをレクチンマイクロアレイにより解析・同定する。選別された複数種のレクチンを用いて食道癌患者および健常者の臨床検体(血液、唾液)中の遊離糖鎖の検出を行い、糖鎖-レクチン反応を標的としたリキッドバイオプシー法による食道癌の早期診断法としての有用性を検証する。また既存マーカーとの感度・特異度の比較を行い、新規バイオマーカーとしての優位性についても検証する。

Outline of Final Research Achievements

We focused on liquid biopsy as an early diagnosis method for esophageal cancer and examined the applicability of glycan-lectin reaction. Using 24 surgical specimens of esophageal squamous cell carcinoma, we comprehensively searched for cancer-specific glycan-lectin combinations and identified UAE1, which binds to α1-2FUC (glycan), as a candidate lectin. Then, we performed lectin blotting with UAE1 lectin using sera from esophageal cancer patients and healthy subjects, and could not detect any specific reaction to esophageal cancer. Although it is highly likely that UAE1 is an esophageal cancer-specific lectin, further studies are needed to validate it as a potential therapeutic biomarker and target.

Academic Significance and Societal Importance of the Research Achievements

食道癌は難治性癌の代表例であり、早期診断・早期治療に勝る治療法はない。癌細胞表面には特徴的な修飾を受けた癌特異的な糖鎖が発現しており、発癌初期から血中や唾液中に糖鎖の構造物が遊離している可能性が高いと考えた。本研究では食道癌に特異的なα1-2FUC(糖鎖)-UAE1(レクチン)を同定することができたが、癌患者の血清中の発現を確認することは出来なかった。検出力を高めるため、またより特異性の高い候補レクチンの探索などさらなる検討を要するが、糖鎖レクチン反応を用いたリキッドバイオプシー臨床応用への足掛かりを得ることができた。

Report

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

    (4 results)

All 2020

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results)

  • [Journal Article] Exploring optimal examination to detect occult anastomotic leakage after rectal resection in patients with diverting stoma.2020

    • Author(s)
      Kitaguchi D, Enomoto T, Ohara Y, Owada Y, Hisakura K, Akashi Y, Takahashi K, Ogawa K, Shimomura O, Oda T.
    • Journal Title

      BMC Surg.

      Volume: 20 Issue: 1 Pages: 53-57

    • DOI

      10.1186/s12893-020-00706-x

    • NAID

      120007127645

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of 2- and 4-week S-1 administration as adjuvant chemotherapy for advanced gastric cancer2020

    • Author(s)
      Ogawa K, Honda M, Akashi Y, Inagawa S, Kaneda A, Hori S, Owada Y, Ohara Y, Hisakura K, Enomoto T, Shimomura O, Takahashi K, Oda T.
    • Journal Title

      Int J Clin Oncol.

      Volume: 25 Issue: 1 Pages: 1807-1813

    • DOI

      10.1186/s13104-020-05022-4

    • NAID

      120007169670

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel Pancreatic Cancer Therapy Targeting Cell Surface Glycans by Liposomes Modified with rBC2LCN Lectin2020

    • Author(s)
      Kimura S, Oda T, Shimomura O, Enomoto T, Hashimoto S, Kuroda Y, Yu Y, Kurimori K, Furuta T, Miyazaki Y, Tateno H.
    • Journal Title

      Eur Surg Res.

      Volume: 61 Issue: 4-5 Pages: 113-122

    • DOI

      10.1159/000513430

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lectin drug conjugate therapy for colorectal cancer2020

    • Author(s)
      Kitaguchi Daichi、Oda Tatsuya、Enomoto Tsuyoshi、Ohara Yusuke、Owada Yohei、Akashi Yoshimasa、Furuta Tomoaki、Yu Yang、Kimura Sota、Kuroda Yukihito、Kurimori Ko、Miyazaki Yoshihiro、Furuya Kinji、Shimomura Osamu、Tateno Hiroaki
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 12 Pages: 4548-4557

    • DOI

      10.1111/cas.14687

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access

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Published: 2019-04-18   Modified: 2022-01-27  

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