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Analysis of amyloid-associated proteins by imaging mass spectrometry using FFPE tissue

Research Project

Project/Area Number 19K16561
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49020:Human pathology-related
Research InstitutionSapporo Medical University

Principal Investigator

Aoyama Tomoyuki  札幌医科大学, 医学部, 研究員 (50737781)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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アミロイド / プロテオミクス / FFPE / アミロイドーシス / IMS / イメージング質量分析
Outline of Research at the Start

本研究では、イメージング質量分析(IMS)技術を基盤とした、アミロイドーシスで異常蓄積する原因蛋白質の同定法、アミロイドーシス病型診断法の確立を目指す。そのために、アミロイドーシスのホルマリン固定パラフィン包埋(formalin fixed paraffin embedded; FFPE)組織を用い、LC-MS/MSによる比較プロテオミクスとIMSを行ない、アミロイドーシスの病型ごとに、得られたペプチドのマススペクトルをデータベース化する。最終的に、IMSデータのパターン分類のみによるアミロイドーシス病型診断システムを構築する。

Outline of Final Research Achievements

We aimed to identify amyloidosis-causing proteins by imaging mass spectrometry (IMS) using FFPE tissue. First, a comparative proteomic analysis was performed in hearts, in amyloidosis cases, and in target cases. A total of 2324 proteins were identified. Multivariate analysis using 678 proteins, which were significantly increased in amyloidosis cases, showed that amyloidosis and control cases were clearly divided into groups. Furthermore, Tissue Microarray slides were prepared for 12 proteins uniquely expressed in amyloidosis cases, and IMS targeting specific MS spectra identified promising peaks.

Academic Significance and Societal Importance of the Research Achievements

本研究は、近年増加傾向にあり、新規治療薬が登場しているアミロイドーシス患者の早期診断、適切な治療法選択に大いに寄与し、有望かつ有効な治療戦略創出のための重要な知見となりうる。本研究により得られる知見の蓄積と発信は、IMSによる in situ proteome analysis とでも言うべき、全く新しい次元の病態理解、診断技術開発への嚆矢となる。また、研究を進める中で、原因物質不明のアミロイドーシス症例をプロテオーム解析することで、最近になり報告された全身性APOA4アミロイドーシスであることが判明し、論文として報告している。アミロイドーシスにおけるプロテオーム解析の有用性が示唆された。

Report

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

    (19 results)

All 2022 2021 2020 2019

All Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 8 results) Presentation (7 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] A systemic apolipoprotein A-IV-associated amyloidosis confirmed by proteome analysis2021

    • Author(s)
      Murakami Taro、Takasawa Akira、Moriki Asako、Igaki Yusuke、Ikeda Hiroshi、Murase Kazuyuki、Takada Kohichi、Magara Kazufumi、Aoyama Tomoyuki、Ono Yusuke、Kyuno Daisuke、Takasawa Kumi、Murata Masaki、Osanai Makoto
    • Journal Title

      Virchows Archiv

      Volume: - Issue: 5 Pages: 1041-1046

    • DOI

      10.1007/s00428-021-03073-x

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulatory roles of claudin-1 in cell adhesion and microvilli formation2021

    • Author(s)
      Takasawa Kumi、Takasawa Akira、Akimoto Taishi、Magara Kazufumi、Aoyama Tomoyuki、Kitajima Hiroshi、Murakami Taro、Ono Yusuke、Kyuno Daisuke、Suzuki Hiromu、Osanai Makoto
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 565 Pages: 36-42

    • DOI

      10.1016/j.bbrc.2021.05.070

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Claudin-18.2 as a therapeutic target in cancers: cumulative findings from basic research and clinical trials2021

    • Author(s)
      Kyuno Daisuke、Takasawa Akira、Takasawa Kumi、Ono Yusuke、Aoyama Tomoyuki、Magara Kazufumi、Nakamori Yuna、Takemasa Ichiro、Osanai Makoto
    • Journal Title

      Tissue Barriers

      Volume: 10 Issue: 1 Pages: 1967080-1967080

    • DOI

      10.1080/21688370.2021.1967080

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of tight junctions in the epithelial-to-mesenchymal transition of cancer cells2021

    • Author(s)
      Kyuno Daisuke、Takasawa Akira、Kikuchi Shin、Takemasa Ichiro、Osanai Makoto、Kojima Takashi
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Biomembranes

      Volume: 1863 Issue: 3 Pages: 183503-183503

    • DOI

      10.1016/j.bbamem.2020.183503

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aberrant expression of junctional adhesion molecule-A contributes to the malignancy of cervical adenocarcinoma by interaction with poliovirus receptor/CD155.2021

    • Author(s)
      Murakami T, Takasawa A, Takasawa K, Akimoto T, Aoyama T, Magara K, Saito Y, Ota M, Kyuno D, Yamamoto S, Hasegawa T, Saito T, Osanai M.
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 2 Pages: 906-917

    • DOI

      10.1111/cas.14734

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aldolase A promotes epithelial-mesenchymal transition to increase malignant potentials of cervical adenocarcinoma.2020

    • Author(s)
      Saito Y, Takasawa A, Takasawa K, Aoyama T, Akimoto T, Ota M, Magara K, Murata M, Hirohashi H, Hasegawa T, Sawada N, Saito T, Osanai M.
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 8 Pages: 3071-3081

    • DOI

      10.1111/cas.14524

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular Aberrations Associated with Seizure Control in Diffuse Astrocytic and Oligodendroglial Tumors2020

    • Author(s)
      Suzuki H, Mikuni N, Sugita S, Aoyama T, Yokoyama R, Suzuki Y, Enatsu R, Akiyama Y, Mikami T, Wanibuchi M, Hasegawa T.
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 60 Issue: 3 Pages: 147-155

    • DOI

      10.2176/nmc.oa.2019-0218

    • NAID

      130007808837

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Detection of VHL deletion by fluorescence in situ hybridization in extraneuraxial hemangioblastoma of soft tissue2020

    • Author(s)
      Segawa Keiko、Sugita Shintaro、Aoyama Tomoyuki、Minami Seiichi、Nagashima Kazuo、 Tsuda Masumi、Tanaka Shinya、Hasegawa Tadashi
    • Journal Title

      Pathology international

      Volume: - Issue: 7 Pages: 473-475

    • DOI

      10.1111/pin.12935

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunoreactivity patterns of tight junction proteins are useful for differential diagnosis of human salivary gland tumors.2019

    • Author(s)
      Aoyama T, Takasawa A, Murata M, Osanai M, Takano K, Hasagawa T, Sawada N.
    • Journal Title

      Med Mol Morphol.

      Volume: 52 Issue: 1 Pages: 23-35

    • DOI

      10.1007/s00795-018-0199-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Imprint cytology of biphenotypic sinonasal sarcoma of the paranasal sinus: A case report2019

    • Author(s)
      Sugita Shintaro、Kubo Terufumi、Aoyama Tomoyuki、Moriya Jun、Okuni Tsuyoshi、Wanibuchi Masahiko、Yamashita Ken、Onodera Maki、Tsujiwaki Mitsuhiro、Segawa Keiko、Sugawara Taro、Hasegawa Tadashi
    • Journal Title

      Diagnostic Cytopathology

      Volume: 47 Issue: 5 Pages: 507-511

    • DOI

      10.1002/dc.24142

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of Coiled-Coil Domain-Containing Protein 180 and Leucine-Rich Repeat-Containing Protein 4 as Potential Immunohistochemical Markers for Liposarcoma Based on Proteomic Analysis Using Formalin-Fixed, Paraffin-Embedded Tissue.2019

    • Author(s)
      Aoyama T, Takasawa A, Takasawa K, Ono Y, Emori M, Murata M, Hayasaka T, Fujitani N, Osanai M, Yamashita T, Hasegawa T, Sawada N.
    • Journal Title

      Am J Pathol.

      Volume: in press Issue: 5 Pages: 1015-1028

    • DOI

      10.1016/j.ajpath.2019.01.013

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Elevated expression of G protein-coupled receptor 30 (GPR30) is associated with poor prognosis in patients with uterine cervical adenocarcinoma2019

    • Author(s)
      Ino Yoshihiko、Akimoto Taishi、Takasawa Akira、Takasawa Kumi、Aoyama Tomoyuki、Ueda Asako、Ota Misaki、Magara Kazufumi、Tagami Yohei、Murata Masaki、Hasegawa Tadashi、Saito Tsuyoshi、 Sawada Norimasa and Osanai Makoto
    • Journal Title

      Histology and histopathology

      Volume: -

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 乳がんにおいて JAM-A の異常高発現が悪性化に関与する2022

    • Author(s)
      真柄和史、高澤啓、高澤久美、青山智志、小野祐輔、及能大輔、小山内誠
    • Organizer
      第111回日本病理学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 悪性神経鞘腫のFFPE組織標本を用いた新規バイオマーカー探索の試み2021

    • Author(s)
      車野晃大、高澤啓、伊藤祐依、桐澤くらら、青山智志、小野祐輔、高澤久美、及能大輔、小山内誠
    • Organizer
      第67回日本病理学会秋期特別総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 乳癌における ALDOA の発現とその病理学的意義2021

    • Author(s)
      桐澤くらら、高澤啓、伊藤祐依、車野晃大、小野祐輔、青山智志、高澤久美、小山内誠
    • Organizer
      第67回日本病理学会秋期特別総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 子宮頸部腺癌における claudin-6 発現とその意義2021

    • Author(s)
      伊藤祐依、高澤啓、桐澤くらら、車野晃大、青山智志、小野祐輔、小山内誠
    • Organizer
      第67回日本病理学会秋期特別総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Aberrant high expression of ALDOA contributes to the malignant transformation of uterine cervical adenocarcinoma2021

    • Author(s)
      Akira takasawa, Yuki saito, Kumi Takasawa, Taishi Akimoto, Kazufumi Magara, Tomoyuki Aoyama, Yusuke Ono, Daisuke Kyuno, Yoshihiko Hirohashi, Tsuyoshi Saito, Makoto Osanai
    • Organizer
      The 39 Sapporo International Cancer Symposium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Roles of claudin-1 in cell adhesion and microvilli formation of cervical adenocarcinoma cells2021

    • Author(s)
      Kumi Takasawa, Akira takasawa, Taishi Akimoto, Kazufumi Magara, Tomoyuki Aoyama, Yusuke Ono, Daisuke kyuno, Makoto Osanai
    • Organizer
      The 39 Sapporo International Cancer Symposium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] FFPE 組織を用いたプロテオミクスによる脂肪肉腫診断マーカーの探索2019

    • Author(s)
      青山 智志、高澤 啓、小野 祐輔、長谷川 匡、小山内 誠
    • Organizer
      第 44 回 日本医用マススペクトル学会年会
    • Related Report
      2019 Research-status Report

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

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