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2022 Fiscal Year Annual Research Report

Early diagnosis of pancreatic cancer based on diversity of field defect and molecular genetic approach

Research Project

Project/Area Number 20H03655
Research InstitutionAsahikawa Medical College

Principal Investigator

水上 裕輔  旭川医科大学, 医学部, 教授 (30400089)

Co-Investigator(Kenkyū-buntansha) 小野 裕介  医療法人徳洲会札幌東徳洲会病院医学研究所, ゲノム診断研究部, 部門長 (40742648)
唐崎 秀則  医療法人徳洲会札幌東徳洲会病院医学研究所, がん生物研究部, 客員研究員 (50374806)
谷上 賢瑞  東京大学, アイソトープ総合センター, 特任准教授 (90648627)
Project Period (FY) 2020-04-01 – 2023-03-31
Keywords膵癌 / 多領域シーケンス / IPMN / 早期診断
Outline of Annual Research Achievements

IPMN関連膵癌患者を対象に、切除材料生材料より腫瘍細胞分画を分離し、RNA-seq解析に加えナノポアによるロングリードシーケンシングを行った。各検体において、病理診断用の固定材料を用い、H-E及びCLDN18免疫染色をもとに、切除対象となった主病変(指標病変)並びに上皮内腫瘍から浸潤癌への移行部、多発病変など組織学的な多様性を確認できる多領域分画(関心領域)を設定し、それぞれについてターゲットシーケンシングによる変異プロファイリングを行った。その結果をもとに低異型度から高異型度病変への進展過程で見られる遺伝子異常の蓄積パターンからクローン類縁性の評価と、病変空間内での進化の時間軸の再構築を試みた。また、同一の腫瘍関心領域について、先進ゲノム支援の協力を得て空間トランスクリプトーム解析を行い、遺伝子変異の分布との対比を進めている。現時点でデータ解析中であり、得られた結果をもって2023年度内の論文報告を予定している。

Research Progress Status

令和4年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和4年度が最終年度であるため、記入しない。

  • Research Products

    (24 results)

All 2023 2022

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 1 results) Presentation (11 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Molecular comparison of concurrent components of high-grade dysplasia, adenocarcinoma, and sarcomatoid carcinoma in a case of sarcomatoid carcinoma of the gallbladder2023

    • Author(s)
      Hirose Katsuya、Omori Yuko、Ono Yusuke、Mizukami Yusuke、Kaneko Yoshiki、Maruyama Tsunehiko、Ohtani Haruo、Furukawa Toru
    • Journal Title

      Virchows Archiv

      Volume: 99 Pages: 99

    • DOI

      10.1007/s00428-023-03524-7

    • Peer Reviewed
  • [Journal Article] GATA6 and CK5 Stratify the Survival of Patients With Pancreatic Cancer Undergoing Neoadjuvant Chemotherapy2023

    • Author(s)
      Kokumai Takashi、Omori Yuko、Ishida Masaharu、Ohtsuka Hideo、Mizuma Masamichi、Nakagawa Kei、Maeda Chiho、Ono Yusuke、Mizukami Yusuke、Miura Shin、Kume Kiyoshi、Masamune Atsushi、Morikawa Takanori、Unno Michiaki、Furukawa Toru
    • Journal Title

      Modern Pathology

      Volume: 36 Pages: 100102~100102

    • DOI

      10.1016/j.modpat.2023.100102

    • Peer Reviewed
  • [Journal Article] Multiplex Digital PCR Assay to Detect Multiple KRAS and GNAS Mutations Associated with Pancreatic Carcinogenesis from Minimal Specimen Amounts2023

    • Author(s)
      Maeda Chiho、Ono Yusuke、Hayashi Akihiro、Takahashi Kenji、Taniue Kenzui、Kakisaka Rika、Mori Miyuki、Ishii Takahiro、Sato Hiroki、Okada Tetsuhiro、Kawabata Hidemasa、Goto Takuma、Tamamura Nobue、Omori Yuko、Takahashi Kuniyuki、Katanuma Akio、Karasaki Hidenori、Liss Andrew Scott、Mizukami Yusuke
    • Journal Title

      The Journal of Molecular Diagnostics

      Volume: 99 Pages: 99

    • DOI

      10.1016/j.jmoldx.2023.02.007

    • Peer Reviewed
  • [Journal Article] Serine/Threonine Kinase 11 Plays a Canonical Role in Malignant Progression of KRAS-Mutant and GNAS-Wild-Type Intraductal Papillary Mucinous Neoplasms of the Pancreas2023

    • Author(s)
      Omori Yuko、Ono Yusuke、Morikawa Takanori、Motoi Fuyuhiko、Higuchi Ryota、Yamamoto Masakazu、Hayakawa Yuko、Karasaki Hidenori、Mizukami Yusuke、Unno Michiaki、Furukawa Toru
    • Journal Title

      Annals of Surgery

      Volume: 277 Pages: e384~e395

    • DOI

      10.1097/SLA.0000000000004842

    • Peer Reviewed
  • [Journal Article] Mutant GNAS limits tumor aggressiveness in established pancreatic cancer via antagonizing the KRAS-pathway2022

    • Author(s)
      H. Kawabata, Y. Ono, N. Tamamura, K. Oyama, J. Ueda, H. Sato, et al.
    • Journal Title

      Journal of Gastroenterology

      Volume: 57 Pages: 208~220

    • DOI

      10.1007/s00535-021-01846-4

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Predictors of Long-Term Survival in Pancreatic Ductal Adenocarcinoma after Pancreatectomy: TP53 and SMAD4 Mutation Scoring in Combination with CA19-92022

    • Author(s)
      M. Ono, Y. Ono, T. Nakamura, T. Tsuchikawa, T. Kuraya, S. Kuwabara, et al.
    • Journal Title

      Annals of Surgical Oncology

      Volume: 29 Pages: 5007~5019

    • DOI

      10.1245/s10434-022-11630-0

    • Peer Reviewed
  • [Journal Article] Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study2022

    • Author(s)
      K. Takada, T. Kubo, J. Kikuchi, M. Yoshida, A. Murota, Y. Arihara, et al.
    • Journal Title

      Frontiers in Oncology

      Volume: 12 Pages: 99

    • DOI

      10.3389/fonc.2022.988527

    • Peer Reviewed
  • [Journal Article] Artificial intelligence?assisted detection of colorectal polyps in Lynch syndrome2022

    • Author(s)
      Tanabe Hiroki、Moriichi Kentaro、Mizukami Yusuke、Fujiya Mikihiro、Okumura Toshikatsu
    • Journal Title

      Gastrointestinal Endoscopy

      Volume: 95 Pages: 1276~1277

    • DOI

      10.1016/j.gie.2022.02.009

    • Peer Reviewed
  • [Journal Article] RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival2022

    • Author(s)
      Taniue Kenzui、Tanu Tanzina、Shimoura Yuki、Mitsutomi Shuhei、Han Han、Kakisaka Rika、Ono Yusuke、Tamamura Nobue、Takahashi Kenji、Wada Youichiro、Mizukami Yusuke、Akimitsu Nobuyoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Pages: 496~496

    • DOI

      10.3390/ijms23010496

    • Peer Reviewed / Open Access
  • [Journal Article] ゲノム解析により膵管内乳頭粘液性腫瘍併存癌の初期像と診断し得た1例.2022

    • Author(s)
      佐藤允洋、唐崎秀則、 富永素矢、 坂本 淳、 木村圭介、 太田智之、 田中伸哉、 水上裕輔.
    • Journal Title

      日本消化器病学会雑誌

      Volume: 119 Pages: 368-376

    • Peer Reviewed
  • [Journal Article] ゲノム解析による膵癌の早期診断.2022

    • Author(s)
      佐藤裕基、高橋賢治、水上裕輔.
    • Journal Title

      膵臓

      Volume: 37 Pages: 29-39

    • Peer Reviewed
  • [Journal Article] IPMN の悪性度評価とliquid biopsy.2022

    • Author(s)
      高橋賢治、大森優子、小野裕介、古川 徹、水上裕輔.
    • Journal Title

      胆と膵

      Volume: 43 Pages: 99

  • [Presentation] Phenotyping and the Combinatorial System by the Number of Accumulated Gene Alterations of Intraductal Papillary Mucinous Neoplasms Stratifies the Risk of Invasion and Outcome: New Insight for Management Strategy.2023

    • Author(s)
      Yuko Omori, Yusuke Ono, Takashi Kokumai, et al.
    • Organizer
      USACAP 112TH ANNUAL MEETING
    • Int'l Joint Research
  • [Presentation] Tumor-suppressive effect of mutant GNAS through the restriction of tumor aggressiveness in established pancreatic cancer.2022

    • Author(s)
      Hidemasa Kawabata, Yusuke Ono, Nobue Tamamura, et al.
    • Organizer
      DDW2022/AGA2022
    • Int'l Joint Research
  • [Presentation] Three molecular development pathways of remnant pancreatic cancer impact survival after resection.2022

    • Author(s)
      Shuji Suzuki, Yuko Omori, Katsuya Hirose, et al.
    • Organizer
      第26回国際膵臓学会 Symposium 1 Advances in genomics for pancreatic neoplasms
    • Int'l Joint Research
  • [Presentation] The application of EV RNA panel as liquid biopsy for pancreatic ductal adenocarcinoma.2022

    • Author(s)
      Kenji Takahashi, Hiroki Sato, Shugo Fujibayashi, et al.
    • Organizer
      第26回国際膵臓学会 Symposium 5 Molecular profiling of pancreatic cancer and application of liquid biopsy to clinical practice
    • Int'l Joint Research
  • [Presentation] Molecular barcode sequencing using duodenal fluid for profiling genomic alterations in pancreatic neoplasms.2022

    • Author(s)
      Yusuke Ono, Kenji Takahashi, Akihiro Hayashi, et al.
    • Organizer
      第26回国際膵臓学会 Panel Discussion 4 Quest for early diagnosis of pancreatic cancer
    • Int'l Joint Research
  • [Presentation] High-sensitive mutation detection in liquid biopsy with duodenal fluid captures genetic mutations associated with pancreatic carcinogenesis.2022

    • Author(s)
      Yusuke Ono, Chiho Maeda, Kenji Takahashi, al.
    • Organizer
      AACR Special Conference on Pancreatic Cancer (Plenary session)
    • Int'l Joint Research / Invited
  • [Presentation] 病理解剖例における膵前癌病変の遺伝子解析/Gene mutation analysis of precancerous lesions of the pancreas.2022

    • Author(s)
      武藤麻理子、小野裕介、山川けいこ、ほか
    • Organizer
      第111回 日本病理学会総会
  • [Presentation] 十二指腸液由来遊離核酸を用いた膵癌リキッドバイオプシーの有用性.2022

    • Author(s)
      高橋 賢治、林 明宏、水上 裕輔.
    • Organizer
      第108回日本消化器病学会総会.  ワークショップ 16:胆膵疾患の遺伝子解析による病態解明・臨床展開
  • [Presentation] 消化液に存在する膵癌由来の遺伝子変異検出を目指したリキッドバイオプシー.2022

    • Author(s)
      Yusuke Ono, Chiho Maeda, Kenji Takahashi, et al.
    • Organizer
      第81回日本癌学会学術総会
  • [Presentation] GNAS変異はKRAS経路に拮抗することにより、膵癌の悪性度を抑える.2022

    • Author(s)
      Hidemasa Kawabata, Yusuke Ono, Kenji Takahashi, et al.
    • Organizer
      第81回日本癌学会学術総会
  • [Presentation] 細胞外小胞によるmiR-425の細胞間伝達は上皮間葉形質転換を促進し膵癌進展を制御する.2022

    • Author(s)
      小山一也、高橋賢治、 藤林周吾、ほか
    • Organizer
      第30回日本消化器関連学会週間
  • [Book] 膵癌・胆道癌 2023 (上) 膵癌編 ―基礎・臨床の最新研究動向― II.各 論 由来癌と併存癌.2023

    • Author(s)
      河端秀賢、高橋賢治、水上裕輔.
    • Total Pages
      99
    • Publisher
      日本臨牀社

URL: 

Published: 2023-12-25  

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