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Pathological diagnosis based on integration of morphological images and multi-layer omics data by artificial intelligence

Research Project

Project/Area Number 21H02705
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionKeio University

Principal Investigator

Kanai Yae  慶應義塾大学, 医学部(信濃町), 教授 (00260315)

Co-Investigator(Kenkyū-buntansha) 榊原 康文  慶應義塾大学, 理工学部(矢上), 教授 (10287427)
新井 恵吏  慶應義塾大学, 医学部(信濃町), 准教授 (40446547)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2023: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Keywords病理診断 / 人工知能 / オミックス解析 / 病理画像 / CpGアイランドメチル化形質
Outline of Research at the Start

本研究は、人工知能 (AI)の支援を受けて病理形態像とゲノム等オミックス情報を融合させ、がんの治療奏効性・有害事象・予後を予測する深層学習モデルを構築することを目的とする。予測時のAIの着眼点を可視化し、形態学的診断基準に翻訳して、病理医が顕微鏡で見るだけでモデルと同等の治療奏効性・有害事象・予後予測を可能にすることを目指す。悪性度が高い腎淡明細胞がんのCpGアイランドメチル化形質 (CIMP)の予測モデルを構築する過程で、病理画像とオミックスデータを統合する至適研究手法を確立し、「病理医とAIの創造的協働による、オミックス情報を統合した新しい病理診断の創出 (病理診断学の革新)」を図る。

Outline of Final Research Achievements

The aim of this study was to build a deep learning model to predict cancer treatment response and prognosis by fusing pathological morphology images and omics information with the assistance of artificial intelligence (AI). Using micrographs and virtual slide data of renal cell carcinoma surgical specimens, a convolutional neural network model of CpG island methylation trait (CIMP)-positive renal cell carcinoma with poor prognosis was constructed. Furthermore, gradient-weighted class activation mapping was used to visualise which regions of the pathological image are focused on when discriminating CIMP-positive and CIMP-negative. Additional multilayer omics information is currently being acquired to improve the prognostic power of the model.

Academic Significance and Societal Importance of the Research Achievements

病理診断は従来から、がん等の臨床症例の最終診断を担ってきたが、がんゲノム医療が社会実装された今日にあっては、従来通り形態像のみに基づく組織型分類にとどまるべきではない。病理診断学は、オミックス情報を取り込んで、ブレイクスルーを果たすべきである。可視化したCIMP判定時のAIの着眼点を形態学的診断基準に翻訳することにより、病理医が顕微鏡で見るだけでモデルと同等の治療奏効性予測・予後予測を実施できれば、「病理医とAIの創造的協働による、オミックス情報を統合した新しい病理診断の創出」の端緒となると期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (41 results)

All 2024 2023 2022 2021 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 13 results) Presentation (21 results) (of which Int'l Joint Research: 3 results,  Invited: 7 results) Remarks (7 results)

  • [Journal Article] Molecular pathological approach to cancer epigenomics and its clinical application2024

    • Author(s)
      Kanai Yae
    • Journal Title

      Pathology International

      Volume: 74 Issue: 4 Pages: 167-186

    • DOI

      10.1111/pin.13418

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA methylation alterations of ADCY5, MICAL2, and PLEKHG2 during the developmental stage of cryptogenic hepatocellular carcinoma2023

    • Author(s)
      Makiuchi Satomi、Tian Ying、Fujimoto Mao、Kuramoto Junko、Tsuda Noboru、Ojima Hidenori、Gotoh Masahiro、Hiraoka Nobuyoshi、Yoshida Teruhiko、Kanai Yae、Arai Eri
    • Journal Title

      Hepatology Research

      Volume: 54 Issue: 3 Pages: 284-299

    • DOI

      10.1111/hepr.13984

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic profile of Japanese supercentenarians: a cross-sectional study.2023

    • Author(s)
      Komaki S, Nagata M, Arai E et al (19人中3番目)
    • Journal Title

      Lancet Healthy Longev

      Volume: 4 Issue: 2 Pages: e83-e90

    • DOI

      10.1016/s2666-7568(23)00002-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantification of DNA methylation for carcinogenic risk estimation in patients with non-alcoholic steatohepatitis.2022

    • Author(s)
      Kuramoto J, Arai E, Fujimoto M et al (19人中2番目)
    • Journal Title

      Clin Epigenetics

      Volume: 14 Issue: 1 Pages: 168-168

    • DOI

      10.1186/s13148-022-01379-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA methylation status of the SPHK1 and LTB genes underlies the clinicopathological diversity of non-alcoholic steatohepatitis-related hepatocellular carcinomas.2022

    • Author(s)
      Tsuda N, Tian Y, Arai E et al (11人中11番目)
    • Journal Title

      J Cancer Res Clin Oncol

      Volume: - Issue: 8 Pages: 1-16

    • DOI

      10.1007/s00432-022-04445-9

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostication of early-onset endometrioid endometrial cancer based on genome-wide DNA methylation profiles.2022

    • Author(s)
      Hirano T, Arai E, Fujimoto M et al (11人中2番目)
    • Journal Title

      J Gynecol Oncol

      Volume: 33 Issue: 6

    • DOI

      10.3802/jgo.2022.33.e74

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The oligodendroglial histological features are not independently predictive of patient prognosis in lower-grade gliomas2022

    • Author(s)
      Pareira Eriel Sandika、Shibuya Makoto、Ohara Kentaro、Nakagawa Yu、Kanazawa Tokunori、Kamamoto Dai、Kato Yasutaka、Arai Eri、Aimono Eriko、Yoshida Kazunari、Nishihara Hiroshi、Kanai Yae、Sasaki Hikaru
    • Journal Title

      Brain Tumor Pathology

      Volume: - Issue: 2 Pages: 79-87

    • DOI

      10.1007/s10014-022-00426-5

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinicopathological impacts of DNA methylation alterations on pancreatic ductal adenocarcinoma: prediction of early recurrence based on genome-wide DNA methylation profiling.2021

    • Author(s)
      Endo Y, Fujimoto M, Ito N, Takahashi Y, Kitago M, Gotoh M, Hiraoka N, Yoshida T, Kitagawa Y, Kanai Y, Arai E.
    • Journal Title

      J Cancer Res Clin Oncol

      Volume: 147 Issue: 5 Pages: 1341-1354

    • DOI

      10.1007/s00432-021-03541-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multi-omic profiling of peritoneal metastases in gastric cancer identifies molecular subtypes and therapeutic vulnerabilities2021

    • Author(s)
      Tanaka Yosuke、Chiwaki Fumiko、Kojima Shinya、Kawazu Masahito、Komatsu Masayuki、Ueno Toshihide、Inoue Satoshi、Sekine Shigeki、Matsusaki Keisuke、Matsushita Hiromichi、Boku Narikazu、Kanai Yae、Yatabe Yasushi、Sasaki Hiroki、Mano Hiroyuki
    • Journal Title

      Nature Cancer

      Volume: 2 Issue: 9 Pages: 962-977

    • DOI

      10.1038/s43018-021-00240-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular classification of gastric cancer predicts survival in patients undergoing radical gastrectomy based on project HOPE2021

    • Author(s)
      Furukawa Kenichiro、Hatakeyama Keiichi、Terashima Masanori、Nagashima Takeshi、Urakami Kenichi、Ohshima Keiichi、Notsu Akifumi、Sugino Takashi、Yagi Taisuke、Fujiya Keiichi、Kamiya Satoshi、Hikage Makoto、Tanizawa Yutaka、Bando Etsuro、Kanai Yae、Akiyama Yasuto、Yamaguchi Ken
    • Journal Title

      Gastric Cancer

      Volume: 25 Issue: 1 Pages: 138-148

    • DOI

      10.1007/s10120-021-01242-0

    • NAID

      40022799797

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Demarcated redness associated with increased vascular density/size: a useful marker of flat-type dysplasia in patients with ulcerative colitis2021

    • Author(s)
      Ikebata Akiyoshi、Shimoda Masayuki、Okabayashi Koji、Uraoka Toshio、Maehata Tadateru、Sugimoto Shinya、Mutaguchi Makoto、Naganuma Makoto、Kameyama Kaori、Yahagi Naohisa、Kanai Takanori、Kitagawa Yuko、Kanai Yae、Iwao Yasushi
    • Journal Title

      Endoscopy International Open

      Volume: 09 Issue: 04 Pages: E552-E561

    • DOI

      10.1055/a-1352-2709

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD163‐positive cancer cells are a predictor of a worse clinical course in lung adenocarcinoma2021

    • Author(s)
      Matsubara Eri、Komohara Yoshihiro、Shinchi Yusuke、Mito Remi、Fujiwara Yukio、Ikeda Koei、Shima Toshiyuki、Shimoda Masayuki、Kanai Yae、Sakagami Takuro、Suzuki Makoto
    • Journal Title

      Pathology International

      Volume: 71 Issue: 10 Pages: 666-673

    • DOI

      10.1111/pin.13144

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Japanese Society of Pathology Practical Guidelines on the handling of pathological tissue samples for cancer genomic medicine2021

    • Author(s)
      Hatanaka Yutaka、Kuwata Takeshi、Morii Eiichi、Kanai Yae、Ichikawa Hitoshi、Kubo Takashi、Hatanaka Kanako C.、Sakai Kazuko、Nishio Kazuto、Fujii Satoshi、Okamoto Wataru、Yoshino Takayuki、Ochiai Atsushi、Oda Yoshinao
    • Journal Title

      Pathology International

      Volume: 71 Issue: 11 Pages: 725-740

    • DOI

      10.1111/pin.13170

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 発がんエピゲノム機構にかかる分子病理学研究2023

    • Author(s)
      金井弥栄
    • Organizer
      第112回日本病理学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 日米の非アルコール性脂肪性肝炎由来肝細胞がんにおけるゲノム網羅的DNAメチル化解析2023

    • Author(s)
      藏本純子、新井恵吏、藤本真央、牧内里美、津田昇、安田和基、平岡伸介、吉田輝彦、Evason Kimberley、金井弥栄
    • Organizer
      第112回日本病理学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 肺腺がんの DNAメチル化プロファイルに対する免疫微小環境の影響2023

    • Author(s)
      河原徹、藤本真央、下田将之、淺村尚生、金井弥栄、新井恵吏
    • Organizer
      第112回日本病理学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 高速液体クロマトグラフィーによる DNAメチル化解析に基づく上部尿路がん新規非侵襲的診断法開発2023

    • Author(s)
      藤本真央、新井恵吏、菊島卓也、西山直隆、中村知史、山田有理子、太平博暁、與谷卓也、北村寛、金井弥栄
    • Organizer
      第112回日本病理学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] DNA methylation diagnostics for upper urinary tract urothelial carcinoma using newly developed high-performance liquid chromatography2023

    • Author(s)
      Mao Fujimoto, Eri Arai, Takuya Kikushima, Naotaka Nishiyama, Tomofumi Nakamura, Yuriko Yamada, Hiroaki Taira, Takuya Yotani, Hiroshi Kitamura, Yae Kanaii
    • Organizer
      America Association for Cancer Research Annual Meeting 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 日米の非アルコール性脂肪性肝炎由来肝細胞がんにおけるゲノム網羅的DNAメチル化解析2023

    • Author(s)
      藏本純子、新井恵吏、藤本真央、牧内里美、津田昇、安田和基、平岡伸介、吉田輝彦、Evason Kimberley、金井弥栄
    • Organizer
      第82回日本癌学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 教育講演2: 泌尿器がんにおけるエピゲノム異常の意義と臨床応用2023

    • Author(s)
      金井弥栄
    • Organizer
      第88回日本泌尿器科学会東部総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Quantification of DNA methylation for carcinogenic risk estimation in patients with non-alcoholic steatohepatitis.2022

    • Author(s)
      Junko Kuramoto, Eri Arai, Mao Fujimoto, Ying Tian, Yuriko Yamada, Takuya Yotani, Satomi Makiuchi, Noboru Tsuda, Hidenori Ojima, Moto Fukai, Yosuke Seki, Kazunori Kasama, Nobuaki Funahashi, Haruhide Udagawa, Takao Nammo, Kazuki Yasuda, Akinobu Taketomi, Tatsuya Kanto, Yae Kanai.
    • Organizer
      American Association for Cancer Research Annual Meeting
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DNAメチル化状態を指標とする非アルコール性脂肪性肝炎からの肝発がんリスク予測.2022

    • Author(s)
      藏本純子、新井恵吏、藤本真央、田迎、牧内里美、津田昇、尾島英知、山田有理子、輿谷卓也、高橋順子、深井原、関洋介、笠間和典、舟橋伸昭、宇田川陽秀、南茂隆生、安田和基、武富紹信、考藤達哉、金井弥栄.
    • Organizer
      第111回日本病理学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 非アルコール性脂肪性肝炎由来肝細胞がんの組織学的多様性に関わるDNAメチル化異常.2022

    • Author(s)
      津田昇、新井恵吏、藏本純子、田迎、牧内里美、尾島英知、高橋順子、平岡伸介、吉田輝彦、金井 弥栄.
    • Organizer
      第111回日本病理学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 非アルコール性脂肪性肝炎由来肝細胞がんにおけるSPHK1ならびにLTB遺伝子の DNAメチル化異常.2022

    • Author(s)
      津田昇、田迎、藤本真央、藏本純子、牧内里美、尾島英知、後藤政広、平岡伸介、吉田輝彦、金井弥栄、新井恵吏.
    • Organizer
      第81回日日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 導性CRISPR/dCas9を用いたC19MC肝内胆管癌オルガノイドの分化における役割の解明.2022

    • Author(s)
      葉子祥、松崎潤太郎、及川千尋、金井弥栄、齋藤義正.
    • Organizer
      第81回日日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 全血由来DNAにおけるエピゲノム関連解析による淡明細胞型腎細胞がんの検出に有用なDNAメチル化バイオマーカー候補の同定.2022

    • Author(s)
      大桃秀樹、新井恵吏、吉田輝彦、金井弥栄、清水厚志.
    • Organizer
      第81回日日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 諸臓器の多段階発がん過程早期に普遍的なDNAメチル化プロファイル.2022

    • Author(s)
      中山雄二、新井恵吏、藤本真央、津田昇、牧内里美、田迎、藏本純子、金井弥栄.
    • Organizer
      第81回日日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 肺腺がんのDNAメチル化プロファイルに対する免疫微小環境の影響.2022

    • Author(s)
      河原徹、藤本真央、下田将之、淺村尚生、金井弥栄、新井恵吏.
    • Organizer
      第81回日日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 多段階発がん過程におけるエピゲノム解析: 病理形態から個別化医療開発へ2021

    • Author(s)
      金井弥栄
    • Organizer
      第110回日本病理学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 病理検体のゲノム・エピゲノム解析で見えるがんの本態: 個別化医療開発に向けて2021

    • Author(s)
      金井弥栄
    • Organizer
      千里ライフサイエンス新適塾「難病への挑戦」
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 個別化治療・予防を目指した病理組織検体におけるエピゲノム解析2021

    • Author(s)
      金井弥栄
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] がんの病理組織検体における多層オミックス統合解析2021

    • Author(s)
      金井弥栄
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 非アルコール性脂肪性肝炎由来肝細胞がんの多段階発生過程におけるDNAメチル化異常2021

    • Author(s)
      金井弥栄
    • Organizer
      Diabetes Scientific Meeting 2021
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Correlations between genome-wide DNA methylation profiles and genomic driver aberrations during multistage lung adenocarcinogenesis2021

    • Author(s)
      Kenichi Hamada, Ying Tian, Mao Fujimoto, Yoriko Takahashi, Takashi Kohno, Koji Tsuta, Shun-ichi Watanabe, Teruhiko Yoshida,Hisao Asamura, Yae Kanai, Eri Arai
    • Organizer
      American Association for Cancer Research Annual Meeting 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 慶應義塾大学医学部病理学教室 (病因病理学分野)・金井研究室

    • URL

      https://pathology.med.keio.ac.jp

    • Related Report
      2023 Annual Research Report
  • [Remarks] Kanai Lab, Dpt Pathol, Keio Univ Sch Med

    • URL

      https://pathology.med.keio.ac.jp/home-e/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 慶應義塾大学医学部病理学教室 (病因病理学分野)金井研究室

    • URL

      https://pathology.med.keio.ac.jp

    • Related Report
      2022 Annual Research Report
  • [Remarks] Kanai Laboratory, Department of Pathology

    • URL

      https://pathology.med.keio.ac.jp/home-e/

    • Related Report
      2022 Annual Research Report
  • [Remarks] これからは病理学でがんを予防する時代

    • URL

      https://www.med.keio.ac.jp/features/2022/12/8-134392/index.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] Pathology Ushers in a New Era of Cancer Prevention

    • URL

      https://www.med.keio.ac.jp/en/features/2023/4/35-137665/index.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] 慶應義塾大学医学部病理学教室金井研究室

    • URL

      https://pathology.med.keio.ac.jp

    • Related Report
      2021 Annual Research Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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