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Elucidation of heterogeneity in pancreatic neuroendocrine tumors using AI and single-cell analysis

Research Project

Project/Area Number 22K08079
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKyushu University

Principal Investigator

Fujimori Nao  九州大学, 大学病院, 講師 (60808137)

Co-Investigator(Kenkyū-buntansha) 竹野 歩  九州大学, 大学病院, 助教 (10812456)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2024: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords膵神経内分泌腫瘍 / 不均一性 / AI / 再発予測モデル / 多施設共同研究 / 人工知能 / Artificial Intelligence / シングルセル解析
Outline of Research at the Start

PanNENは根治術後の再発率が高く、経過も多様性に富む非常に不均一な悪性腫瘍である。また、AIの医療応用は目覚ましいが、PanNEN領域の臨床応用は限定されている。我々はPanNENの病態解明を目標として、九州・四国の西日本広域を対象に国内最大規模のデータベースを構築する多施設共同研究を立ち上げた。本データベースを利用して、AIを用いたPanNEN術後再発予測モデルを構築し、再発や治療応答性といった時間的・薬理学的な腫瘍の不均一性を解析する。PanNEN術後組織を用いたシングルセル解析を併用することで、細胞レベルの不均一性を解析し、PanNEN増悪・進展に関わる因子を明らかにする。

Outline of Final Research Achievements

The aim of this study is to elucidate the heterogeneity of pancreatic neuroendocrine neoplasms (PanNENs). We established a multicenter database of 573 patients with PanNENs, who underwent resection at 22 Japanese centers, mainly in the Kyushu region (Q-P NET registry). The recurrence rate after curative resection of PanNENs increased with higher tumor grade, from NET G1 to G2, G3, and NEC. We extracted 371 patients with localized non-functioning PanNETs (G1/G2). Fifty-two patients experienced recurrence (14.0%) during the follow-up period. We also constructed a machine learning-based prediction model to analyze the important features to determine recurrence. The random survival forest (RSF) model showed better predictive performance than the Cox proportional hazards regression model in terms of the Harrell’s C-index (0.841 vs. 0.820). Similarly, in the analysis of time-dependent area under the receiver operator curve, the RSF model was superior to the Cox model at all time points.

Academic Significance and Societal Importance of the Research Achievements

PanNENはサイズが小さく長期間変化しない症例から、全身転移をきたして急速に悪化する症例まで、非常に不均一な悪性腫瘍である。本研究により術後再発例の臨床的特徴を明らかとし、AIによるPanNEN術後再発予測モデルを構築したことは、PanNEN治療方針を決定する際の一助となる。PanNENは膵癌より若年発症が多いことから、その本態を解明することは社会的意義も大きいと言える。今後シングルセル解析を継続することで、不均一性を解明する必要がある。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (8 results)

All 2025 2024 2023 2022

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Usefulness of Semiautomated 3D Volumetric Assessment of Liver Tumor Burden for Patients With Unresectable Pancreatic Neuroendocrine Tumor2025

    • Author(s)
      Fujimori Nao、Fujita Nobuhiro、Murakami Masatoshi、Ohno Akihisa、Matsumoto Kazuhide、Teramatsu Katsuhito、Ueda Keijiro、Wada Noriaki、Takao Seiichiro、Okamoto Daisuke、Ishigami Kousei、Ito Tetsuhide、Ogawa Yoshihiro
    • Journal Title

      Pancreas

      Volume: 54 Issue: 2 Pages: e122-e129

    • DOI

      10.1097/mpa.0000000000002413

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy and safety of streptozocin-based chemotherapy for gastroenteropancreatic neuroendocrine tumors in Japanese clinical practice2024

    • Author(s)
      Murakami Masatoshi、Fujimori Nao、Takamatsu Yu、Ito Tetsuhide、Matsumoto Kazuhide、Kakehashi Shotaro、Ohno Akihisa、Teramatsu Katsuhito、Ueda Keijiro、Ishigami Kousei、Ogawa Yoshihiro
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 54 Issue: 6 Pages: 647-657

    • DOI

      10.1093/jjco/hyae026

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two cases of pancreatic neuroendocrine tumors with ectopic ACTH syndrome during their disease course2024

    • Author(s)
      Murakami Masatoshi、Hirahata Keisuke、Fujimori Nao、Yamamoto Takeo、Oda Yoshinao、Kozono Shingo、Ueda Keijiro、Ito Testuhide、Nakamura Masafumi、Ogawa Yoshihiro
    • Journal Title

      Clinical Journal of Gastroenterology

      Volume: 17 Issue: 2 Pages: 363-370

    • DOI

      10.1007/s12328-023-01908-5

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AIを用いた膵神経内分泌腫瘍治癒切除後再発予測モデルの構築と分析2024

    • Author(s)
      藤森 尚、村上 正俊、蓑田 洋介、植田 圭二郎、伊藤 鉄英、小川 佳宏
    • Journal Title

      胆と膵

      Volume: 45 Pages: 85-93

    • Related Report
      2023 Research-status Report
  • [Journal Article] Machine learning-based model for prediction and feature analysis of recurrence in pancreatic neuroendocrine tumors G1/G22023

    • Author(s)
      Murakami Masatoshi、Fujimori Nao、Nakata Kohei、et al
    • Journal Title

      Journal of Gastroenterology

      Volume: 58 Issue: 6 Pages: 586-597

    • DOI

      10.1007/s00535-023-01987-8

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 機械学習を用いた膵神経内分泌腫瘍治癒切除後の再発予測因子の解析2023

    • Author(s)
      村上 正俊、藤森 尚、中村雅史、橋元慎、西原一善、階子俊平、小澤栄介、岡本和久、石田祐介、岡野圭一、髙木亮、 小川佳宏
    • Organizer
      第54回日本膵臓学会大会
    • Related Report
      2023 Research-status Report
  • [Presentation] Predictive factors of recurrence after curative resection in patients with PanNET; A multicenter retrospective study2022

    • Author(s)
      Nao Fujimori, Masatoshi Murakami, Takamasa Oono, Masafumi Nakamura, Shinichi Hashimoto, Kazuyoshi Nishihara, Shunpei Hashigo, Eisuke Ozawa, Kazuhisa Okamoto, Yusuke Ishida, Keiichi Okano, Ryo Takaki
    • Organizer
      IAP & JPS 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膵神経内分泌腫瘍治癒切除後の 再発予測因子の検討 ;多施設後方視的研究2022

    • Author(s)
      村上正俊、藤森尚、大野隆真 、中村雅史、橋元慎一、西原一善、階子俊平、小澤栄介、岡本和久、石田祐介、岡野圭一、高木亮、小川佳宏
    • Organizer
      第119回日本消化器病学会九州支部例会
    • Related Report
      2022 Research-status Report

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Published: 2022-04-19   Modified: 2026-01-16  

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