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Establishment of early diagnosis and treatment effect prediction method for pancreatobiliary neoplasm

Research Project

Project/Area Number 18K07019
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionKagoshima University

Principal Investigator

Higashi Michiyo  鹿児島大学, 医歯学域鹿児島大学病院, 准教授 (60315405)

Co-Investigator(Kenkyū-buntansha) 横山 勢也  鹿児島大学, 医歯学域医学系, 助教 (20569941)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords病理学 / 膵胆道腫瘍 / ムチン抗原 / 予後因子 / 機械学習 / MUC1 / MUC4 / MUC / methylation / prognosis / 膵胆道系腫瘍 / 病理 / 膵胆管系腫瘍 / 早期診断 / 治療効果判定 / ムチン
Outline of Final Research Achievements

We had reported that expression profiles of mucins (MUC1, MUC2 and MUC4) are closely associated with biological behavior of human pancreatobiliary neoplasms. We evaluated the methylation status of MUC1, MUC2, and MUC4 promoter regions in pancreatic tissue samples from patients with various pancreatic lesions using methylation-specific electrophoresis. Then, integrating these results and clinicopathological features, we used support vector machine-, neural network-, and multinomial-based methods to develop a prognostic classifier.Significant differences were identified between the positive- and negative-prediction classifiers of patients in 5-year overall survival in the cross-validation test. Multivariate analysis revealed that these prognostic classifiers were independent prognostic factors analyzed by not only neoplastic tissues but also non-neoplastic tissues.

Academic Significance and Societal Importance of the Research Achievements

膵切除検体を用いて各種ムチンの免疫染色結果とDNAメチル化の解析結果が相関していることを示した。またそれらが予後と密接に相関していることを示した。特に腫瘍部のみならず非腫瘍部の組織を用いた解析でも、予後予測因子となり得ることを示した。これは、腫瘍が直接得られない場合でも、非腫瘍部の組織が得られれば予後予測が可能になる可能性を示している。低侵襲の検査や処置ですむ可能性があり、患者負担の軽減のみならず、医療者の負担や医療資源のコスト減にも繋がる可能性がある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (15 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (5 results) (of which Invited: 1 results) Book (1 results)

  • [Int'l Joint Research] University of Nebraska Medical Center/Eppley Institute(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Ulm University(ドイツ)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] A deep learning model to detect pancreatic ductal adenocarcinoma on endoscopic ultrasound-guided fine-needle biopsy2021

    • Author(s)
      Yoshiki Naito, Masayuki Tsuneki , Noriyoshi Fukushima , Yutaka Koga , Michiyo Higashi , 他23名
    • Journal Title

      Sci Rep

      Volume: 19 Issue: 1 Pages: 8454-8454

    • DOI

      10.1038/s41598-021-87748-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Predicted Prognosis of Pancreatic Cancer Patients by Machine Learning.2020

    • Author(s)
      Seiya Yokoyama, Taiji Hamada, Michiyo Higashi, Kei Matsuo, Kousei Maemura, Hiroshi Kurahara, Michiko Horinouchi, Tsubasa Hiraki, Tomoyuki Sugimoto, Toshiaki Akahane, Suguru Yonezawa, Marko Kornmann, Surinder K Batra, Michael A Hollingsworth, Akihide Tanimoto
    • Journal Title

      Clinical cancer research

      Volume: - Issue: 10 Pages: 2411-2421

    • DOI

      10.1158/1078-0432.ccr-19-1247

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lung recurrence and its therapeutic strategy in patients with pancreatic cancer2020

    • Author(s)
      Kurahara Hiroshi、Maemura Kosei、Mataki Yuko、Tanoue Kiyonori、Iino Satoshi、Kawasaki Yota、Idichi Tetsuya、Arigami Takaaki、Mori Shinichiro、Shinden Yoshiaki、Higashi Michiyo、Ueno Shinichi、Shinchi Hiroyuki、Natsugoe Shoji
    • Journal Title

      Pancreatology

      Volume: 20 Issue: 1 Pages: 89-94

    • DOI

      10.1016/j.pan.2019.11.015

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comprehensive validation of liquid-based cytology specimens for next-generation sequencing in cancer genome analysis.2019

    • Author(s)
      Akahane T, Yamaguchi T, Kato Y, Yokoyama S, Hamada T, Nishida Y, Higashi M, Nishihara H, Suzuki S, Ueno S, Tanimoto A.
    • Journal Title

      PloS one.

      Volume: 14 Issue: 6 Pages: 0217724-0217724

    • DOI

      10.1371/journal.pone.0217724

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular volume fraction determined by equilibrium contrast-enhanced multidetector computed tomography as a prognostic factor in unresectable pancreatic adenocarcinoma treated with chemotherapy2019

    • Author(s)
      Fukukura, Y. Kumagae, Y. Higashi, R. Hakamada, H. Takumi, K. Maemura, K. Higashi, M. Kamimura, K. Nakajo, M. Yoshiura, T.
    • Journal Title

      Eur Radiol

      Volume: 29 Issue: 1 Pages: 353-361

    • DOI

      10.1007/s00330-018-5570-4

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CT and MRI features of undifferentiated carcinomas with osteoclast-like giant cells of the pancreas: a case series2019

    • Author(s)
      Fukukura, Y. Kumagae, Y. Hirahara, M. Hakamada, H. Nagano, H. Nakajo, M. Kamimura, K. Nakajo, M. Higashi, M. Yoshiura, T.
    • Journal Title

      Abdominal radiology

      Volume: 44 Issue: 4 Pages: 1246-1255

    • DOI

      10.1007/s00261-019-01958-9

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PCP4/PEP19 upregulates aromatase gene expression via CYP19A1 promoter I.1 in human breast cancer SK-BR-3 cells2018

    • Author(s)
      Honjo Kie、Hamada Taiji、Yoshimura Takuya、Yokoyama Seiya、Yamada Sohsuke、Tan Yan-Qin、Leung Lai K.、Nakamura Norifumi、Ohi Yasuyo、Higashi Michiyo、Tanimoto Akihide
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 51 Pages: 29619-29633

    • DOI

      10.18632/oncotarget.25651

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] DNAメチル化解析結果を用いた計算機科学による膵癌予後予測2021

    • Author(s)
      横山勢也、東美智代、谷本昭英
    • Organizer
      日本癌学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 胆道・膵臓腫瘍の遺伝子異常と病理診断 胆道・膵腫瘍の早期診断とバイオマーカー2020

    • Author(s)
      東 美智代, 横山 勢也, 平木 翼, 北薗 育美, 霧島 茉莉, 田中 貴子, 濱田 一正, 堀之内 道子, 米澤 傑, 谷本 昭英
    • Organizer
      日本病理学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Predicted Prognosis of Pancreatic Cancer Patients by Machine Learning.2019

    • Author(s)
      横山勢也 東 美智代, 谷本 昭英
    • Organizer
      日本癌学会
    • Related Report
      2019 Research-status Report
  • [Presentation] PDAC摘出術後におけるムチン遺伝子のメチル化解析を用いた予後予測法の構築2018

    • Author(s)
      横山 勢也, 東 美智代, 谷本 昭英
    • Organizer
      日本癌学会
    • Related Report
      2018 Research-status Report
  • [Presentation] MUC1およびMUC4遺伝子のメチル化解析による膵癌摘出術後の予後評価2018

    • Author(s)
      横山 勢也, 東 美智代, 谷本 昭英
    • Organizer
      日本病理学会
    • Related Report
      2018 Research-status Report
  • [Book] 胆と膵 IPMN大全 IPMNの歴史的変遷 IPMNにおけるMUC発現とその評価の歴史2020

    • Author(s)
      東美智代、横山勢也、米澤傑、谷本昭英
    • Total Pages
      58
    • Publisher
      医学図書出版
    • ISBN
      9784865173956
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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