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Molecular signature-based classification of circulating tumor cells and its clinical application for refinement of multidisciplinary treatment of pancreatic cancer.

Research Project

Project/Area Number 19K09209
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionYamagata University

Principal Investigator

Motoi Fuyuhiko  山形大学, 医学部, 教授 (30343057)

Co-Investigator(Kenkyū-buntansha) 古川 徹  東北大学, 医学系研究科, 教授 (30282122)
畠 達夫  東北大学, 医学系研究科, 大学院非常勤講師 (30806237)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords膵癌 / 血中循環腫瘍細胞 / 循環腫瘍細胞 / プレシジョン医療 / 集学的治療
Outline of Research at the Start

切除を企図した膵癌の集学的治療にリキッドバイオプシーに基づいたプレシジョン医療を導入することが重要である。本研究は、マルチカラー解析と陽性細胞を繰り返しソートする純化技術を用いて血中循環腫瘍細胞(CTC)を高精度に単離することで、これまでの報告にはない、発現マーカーに基づくCTCのサブタイプ分類とそれぞれの変異、発現、パスウェイなどの特徴、いわゆる分子署名を明らかにすることを目的とし、更に分子署名から創出されたバイオマーカーの有用性を微小転移診断、治療効果予測、病勢モニタリングなどの点から明らかにし、将来的なプレシジョン医療の具現化への橋渡しを目指す。

Outline of Final Research Achievements

In pancreatic cancer, tumor-derived DNA (ctDNA) is more easily detected in the peritoneal washing fluid than in the peripheral blood, and CY ctDNA-positive cases have a significantly poorer prognosis than negative cases, suggesting that CY ctDNA is a useful biomarker reflecting minimal residual disease. Exosomes were isolated from CY and analyzed for exosomal protein markers. miRNA was also extracted and its expression was examined using digital PCR, and miR-21 was found to be more highly expressed in the CY-positive group. Exosome fractions contain consentrated tumor-derived nucleic acids (DNA&RNA) and should be evaluated for useful samples.

Academic Significance and Societal Importance of the Research Achievements

既知の腫瘍マーカーが全ての膵癌症例のおいてその病勢を正確に反映しているとは限らないため、微小転移診断、治療効果予測、病勢モニタリングなどの用途に応じた、より高精度なバイオマーカーの同定・開発が求められる。本研究では、通常診療で侵襲なく得られる腹腔洗浄液により、得られたサンプルがバイオマーカーとして介入法決断・予後予測に有用である可能性を示唆した。難治癌の代表である膵癌診断・治療技術の進歩に寄与できた。

Report

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

    (14 results)

All 2022 2021 2020

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (6 results)

  • [Journal Article] Impact of Tumor-Derived DNA Testing in Peritoneal Lavage of Pancreatic Cancer Patients with and Without Occult Intra-Abdominal Metastases.2022

    • Author(s)
      Chiba K, Hata T, Mizuma M, Masuda K, Aoki S, Takadate T, Kawaguchi K, Nakagawa K, Morikawa T, Motoi F, Furukawa T, Unno M.
    • Journal Title

      Ann Surg Oncol.

      Volume: 29 Issue: 4 Pages: 2685-2697

    • DOI

      10.1245/s10434-021-10997-w

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA-593-3p Expression in Peritoneal Lavage Fluid as a Prognostic Marker for Pancreatic Cancer Patients Undergoing Staging Laparoscopy.2021

    • Author(s)
      Hata T, Mizuma M, Masuda K, Chiba K, Ishida M, Ohtsuka H, Nakagawa K, Morikawa T, Kamei T, Unno M.
    • Journal Title

      Ann Surg Oncol.

      Volume: 28 Issue: 4 Pages: 2235-2245

    • DOI

      10.1245/s10434-020-09440-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Circulating tumor DNA as a predictive marker for occult metastases in pancreatic cancer patients with radiographically non-metastatic disease.2021

    • Author(s)
      Hata T, Mizuma M, Iseki M, Takadate T, Ishida M, Nakagawa K, Hayashi H, Morikawa T, Motoi F, Unno M.
    • Journal Title

      J Hepatobiliary Pancreat Sci.

      Volume: 28 Issue: 8 Pages: 648-658

    • DOI

      10.1002/jhbp.993

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Germline DNA damage repair gene mutations in pancreatic cancer patients with personal/family histories of pancreas/breast/ovarian/prostate cancer in a Japanese population.2021

    • Author(s)
      Hata T, Mizuma M, Motoi F, Ishida M, Ohtsuka H, Nakagawa K, Morikawa T, Furukawa T, Unno M.
    • Journal Title

      Ann Gastroenterol Surg.

      Volume: 5 Issue: 6 Pages: 853-864

    • DOI

      10.1002/ags3.12482

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum Anti-p53 Antibody Can Serve as a Predictive Marker for Histological Grade of Intraductal Papillary Mucinous Neoplasms of the Pancreas.2020

    • Author(s)
      Hata T, Mizuma M, Motoi F, Iseki M, Omori Y, Hayashi H, Nakagawa K, Morikawa T, Kamei T, Naitoh T, Furukawa T, Unno M.
    • Journal Title

      Pancreas.

      Volume: 49 Issue: 6 Pages: 768-773

    • DOI

      10.1097/mpa.0000000000001570

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic impact of intraoperative peritoneal cytology after neoadjuvant therapy for potentially resectable pancreatic cancer.2020

    • Author(s)
      Aoki S, Mizuma M, Hayashi H, Yoshimachi S, Hata T, Miura T, Takadate T, Maeda S, Ariake K, Kawaguchi K, Masuda K, Ishida M, Ohtsuka H, Nakagawa K, Morikawa T, Motoi F, Unno M.
    • Journal Title

      Pancreatology.

      Volume: 20 Issue: 8 Pages: 1711-1717

    • DOI

      10.1016/j.pan.2020.08.022

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic value of FDG-PET radiomics with machine learning in pancreatic cancer.2020

    • Author(s)
      Toyama Y, Hotta M, Motoi F, Takanami K, Minamimoto R, Takase K.
    • Journal Title

      Surg Today.

      Volume: 10 Issue: 1 Pages: 17024-17024

    • DOI

      10.1038/s41598-020-73237-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] GNAS mutation detection in circulating cell-free DNA is a specific predictor for intraductal papillary mucinous neoplasms of the pancreas, especially for intestinal subtype.2020

    • Author(s)
      Hata T, Mizuma M, Motoi F, Omori Y, Ishida M, Nakagawa K, Hayashi H, Morikawa T, Kamei T, Furukawa T, Unno M.
    • Journal Title

      Sci Rep.

      Volume: 10 Issue: 1 Pages: 17761-17761

    • DOI

      10.1038/s41598-020-74868-2

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] BRCA関連腫瘍の既往歴と家族歴に着目した生殖細胞系列変異陽性膵癌の特徴2021

    • Author(s)
      畠 達夫, 水間正道, 元井冬彦, 石田晶玄, 大塚英郎, 中川 圭, 森川孝則, 古川 徹, 海野倫明
    • Organizer
      第52回日本膵臓学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 膵病変の鑑別診断における膵液中のKRAS遺伝子変異の検出と連続膵液細胞診の併用の有用性2021

    • Author(s)
      畠達夫, 水間正道, 大沼忍, 江川新一, 海野倫明
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] MicroRNA-593-3p expression in peritoneal lavage fluid as a prognostic marker for pancreatic cancer patients undergoing staging laparoscopy2021

    • Author(s)
      Tatsuo Hata, Masamichi Mizuma, Kunihiro Masuda, Kazuharu Chiba, Masaharu Ishida, Hideo Ohtsuka, Kei Nakagawa, Hiroki Hayashi, Takanori Morikawa, Michiaki Unno
    • Organizer
      第33回日本肝胆膵外科学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 初診時切除不能膵癌に対する非手術療法奏効後切除の前向き観察研究:Prep042021

    • Author(s)
      元井冬彦, 中森正二, 松本逸平, 里井壯平, 平野聡, 川畑康成, 庄雅之, 本田五郎, 木村康利, 岸和田昌之, 青笹季文, 岡野圭一, 北川裕久, 村上義昭, 海野倫明
    • Organizer
      第51回日本膵臓学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 膵癌に対する集学的治療2020

    • Author(s)
      元井冬彦
    • Organizer
      第82回日本臨床外科学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 切除不能膵癌に対するConversion Surgeryの適応指標2020

    • Author(s)
      元井冬彦, 大塚英郎, 水間正道, 中川圭, 林洋毅, 森川孝則,亀井尚, 内藤剛, 海野倫明.
    • Organizer
      第75回日本消化器外科学会総会
    • Related Report
      2020 Research-status Report

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

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