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Identifications of pancreatic cancer specific neo-antigens with the autoantibodiomics and verifications of diagnostic utilities of its autoantibody screening to neo-antigens

Research Project

Project/Area Number 19K07928
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionOsaka Medical and Pharmaceutical University

Principal Investigator

NAKANISHI TOYOFUMI  大阪医科薬科大学, 研究支援センター, 准教授 (10247843)

Co-Investigator(Kenkyū-buntansha) 高折 恭一  京都大学, 医学研究科, 准教授 (10329485)
増井 俊彦  京都大学, 医学研究科, 准教授 (20452352)
五十嵐 一雄  近畿大学, 医学部, 非常勤講師 (80098467)
松村 洋子 (田伏洋子)  大阪医科薬科大学, 医学部, 講師 (80388256)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords膵臓癌診断マーカー / 特異抗原 / 自己抗体 / 自己抗体スクリーニング / 検査診断技術 / ネオ抗原 / スクリーニング / 膵臓癌得意抗原 / トリオースリン酸イソメラーぜ / ELISA法 / 膵臓癌特異抗原 / 変異トリオースリン酸イソメラーゼ / ネオ抗原ペプチド / 検査診断法
Outline of Research at the Start

膵臓癌は、悪性新生物による死亡数の第4位を占め、発見時には既に浸潤・転移を伴う進行癌で極めて予後不良である。高折(分担者)は、Hruban教授と共にPancreatic intraepithelial neoplasia(PanIN)分類による膵臓癌早期発見・診断を目指し、臨床経験や学術的研究を重ねて来ている。そこで、PanIN病変から膵臓癌へ移行する分子機構の解明と精度の高い分子マーカーを見出すことが出来れば、膵臓癌の早期診断・根治療法の確立への道が開けてくる。今回、同手法を用いた膵臓癌特異トリオースリン酸イソメラーゼ由来ネオ抗原ペプチドの同定と対応自己抗体スクリーニング法を確立し、その検査診断学的有用性を検証する。

Outline of Final Research Achievements

A human pancreatic cancer cultured cell soluble fraction was used as a pancreatic cancer-specific antigen, a pancreatic disease patient serum was used as a primary antibody, a specific band was found by electrophoresis / western blot / ECL detection, and the 34th Val was further structurally analyzed. Was identified as a TPI mutated to IIe. This mutation is located in the vicinity of the melanoma-specific neoantigen, suggesting the possibility of a new pancreatic cancer-specific antigen. Next, the ELISA method was established and screening was carried out. The sera of healthy subjects had a detection sensitivity or less, and the quantitative values of pancreatic cancer were consistent with the PanIN classification, and it was considered that they could be applied to the differential test for pancreatic diseases.

Academic Significance and Societal Importance of the Research Achievements

膵臓癌は、悪性新生物による死亡数の第4位を占め、発券時には既に浸潤・転移を伴う進行癌で極めて予後不良である。其処で、感度・特異度の高い分子マーカーを見出せれば、早期診断・根治療法の道が開ける。今回のTPIネオ抗原によるELISA法によるスクリーニングは鑑別診断への応用可能な検査技術の確立への大きな第一歩となるであろう。

Report

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

    (5 results)

All 2021 2020

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (2 results)

  • [Journal Article] Application of MALDI-TOF MS analysis for rapid discrimination of free immunoglobulin light chains, kappa and lambda isotypes in patients with monoclonal immunoglobulin gammopathy.2021

    • Author(s)
      Asano S, Masutani R, Ueda K, Igarashi K, Nirasawa T, Kubota M, Tabushi-Matsumura Y, Osaka N, Nakanishi T*
    • Journal Title

      Medical Mass Spectrometry

      Volume: 5(1) Pages: 47-54

    • NAID

      130008062720

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of SARS-CoV-2 RNA quantification by RT-LAMP compared to RT-qPCR2021

    • Author(s)
      Minami Kenta、Masutani Ryota、Suzuki Youichi、Kubota Meri、Osaka Naofumi、Nakanishi Toyofumi、Nakano Takashi、Ukimura Akira
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 27 Issue: 7 Pages: 1068-1071

    • DOI

      10.1016/j.jiac.2021.05.004

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of nine proteins in whole lung extract derived from bleomycin-induced interstitial pneumonia model mouse by two-dimensional electrophoresis/in-gel digestion/ MALDI-TOF MSMS analysis.2021

    • Author(s)
      Ishida T, Kotani T, Tabushi-Matsumura Y, Nakanishi T, Takeuchi T.
    • Journal Title

      Medical Mass Spectrometry

      Volume: 5(1) Pages: 1-9

    • NAID

      130008062716

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] MALDI-TOFMS法による尿中単クローン性免疫グロブリンκ/λ鎖の迅速検出法の確立2020

    • Author(s)
      麻野秀一、中西豊文、五十嵐一雄
    • Organizer
      第45回日本医用マススペクトル学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] MALDI-TOFMS法による尿中単クローン性免疫グロブリン軽鎖のスクリーニング法の確立2020

    • Author(s)
      麻野秀一、中西豊文
    • Organizer
      第67回日本臨床検査医学会学術集会
    • Related Report
      2020 Research-status Report

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

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