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Exploring molecular biological mechanisms involved in SATB2 expression in IBD-related neoplasms

Research Project

Project/Area Number 20K16170
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Iwaya Mai  信州大学, 学術研究院医学系(医学部附属病院), 講師 (70850361)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Keywords炎症性腸疾患 / 大腸癌 / SATB2 / 炎症性発癌 / Claudin 18.2 / 小腸癌 / 炎症性腸疾患関連腫瘍 / Claudin 18 / 潰瘍性大腸炎 / クローン病 / 腸炎関連癌 / 腺癌
Outline of Research at the Start

近年増加傾向である潰瘍性大腸炎やクローン病などの炎症性腸疾患を背景とする腸炎関連癌の発癌メカニズムについての検討を行う。
腸炎関連癌の発症は、繰り返される粘膜障害に伴う遺伝子変異と密接に関連していると考えられている。またIBDを含む多くの炎症性疾患における発癌には、メチル化異常が関与していることが知られている。腸炎関連癌では大腸マーカーであるSATB2の発現低下が知られており、SATB2発現低下はリンパ節転移と関連があるが、SATB2発現低下のメカニズムは未だ明らかとなっていない。
本研究ではSATB2の陰転化のメカニズムについて、メチル化異常を含めた分子生物学的解析、臨床病理学的検討を行う。

Outline of Final Research Achievements

To clarify the correlation between morphological and molecular biological findings in inflammatory bowel disease-associated carcinomas (CACs), immunohistochemical analysis, RNA sequencing, and DNA methylation analysis were performed. We found SATB2-negative CAC and SATB2-positive CAC have approximately 600 differentially expressed genes, and analyzed methylation patterns in the promoter region of the SATB2 gene. CAC tends to show gastric phenotype and we found that CAC significantly expresses Claudin 18.2. The findings suggest that CACs might be a candidate for zolbetuximab, an anti-Claudin 18.2 monoclonal antibody therapy

Academic Significance and Societal Importance of the Research Achievements

腸炎関連大腸癌(CAC)において、SATB2の陰転化が予後と相関する可能性が示されているが、SATB2陽性例と陰性例で、複数の遺伝子において有意に発現量が異なる事を明らかとし、CACにおいてSATB2が特異なバイオマーカーであることを検証した。今後、SATB2陰転化機序を明らかとすることで、CACの病態についてより迫れる可能性が高まった。また、CACでは散発性大腸癌と比して有意にClaudin18.2を発現している事を明らかとし、抗Claudin18.2抗体であるzolbetuximabがCACにおける治療選択肢となり得る可能性を示唆した。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (14 results)

All 2024 2023 2022 2021 2020

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 4 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Case report: Successful treatment with canakinumab of a patient with active ileitis associated with familial Mediterranean fever2024

    • Author(s)
      Dai Kishida, Ryosuke Hara, Takanori Ichikawa, Mai Iwaya, Yasuhiro Shimojima, Yoshiki Sekijima
    • Journal Title

      International Journal of Rheumatic Diseases

      Volume: 27 Issue: 1

    • DOI

      10.1111/1756-185x.15006

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Artificial intelligence for evaluating the risk of gastric cancer: reliable detection and scoring of intestinal metaplasia with deep learning algorithms2023

    • Author(s)
      Iwaya Mai、Hayashi Yuichiro、Sakai Yasuhiro、Yoshizawa Akihiko、Iwaya Yugo、Uehara Takeshi、Kitagawa Masanobu、Fukayama Masashi、Mori Kensaku、Ota Hiroyoshi
    • Journal Title

      Gastrointestinal Endoscopy

      Volume: 98 Issue: 6 Pages: 925-933

    • DOI

      10.1016/j.gie.2023.06.056

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased GS‐II lectin binding and SATB2 downregulation are biological features for sessile serrated lesions and microvesicular hyperplastic polyps2023

    • Author(s)
      Hisanori Matoba, Mai Iwaya, Yoshiko Sato, Noriyasu Kobayashi, Haruka Takemura, Yusuke Kouno, Ayumi Karasawa, Jun Nakayama
    • Journal Title

      Pathology International

      Volume: 73 Issue: 6 Pages: 1-9

    • DOI

      10.1111/pin.13321

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ARL4C is associated with epithelial-to-mesenchymal transition in colorectal cancer2023

    • Author(s)
      Ryo Kanai, Takeshi Uehara , Takahiro Yoshizawa, Masato Kamakura, Tomoyuki Nakajima, Yasuhiro Kinugawa, Mai Iwaya, Shiho Asaka, Masato Kitazawa, Tadanobu Nagaya, Hiroyoshi Ota
    • Journal Title

      BMC cancer

      Volume: 23 Issue: 1 Pages: 478-478

    • DOI

      10.1186/s12885-023-10958-4

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum positivity of serum anti-tissue transglutaminase immunoglobulin A antibodies in Japanese children with inflammatory bowel disease2023

    • Author(s)
      Kurasawa S, Sado T, Kato S, Iwaya M, Nakayama Y.
    • Journal Title

      Pediatr Int

      Volume: 65(1) Issue: 1

    • DOI

      10.1111/ped.15485

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Number and distribution of eosinophils and lymphocytes in the Japanese pediatric gastrointestinal tract: in search of a definition for "abnormally increased eosinophils"2023

    • Author(s)
      Iwaya M, Kobayashi S, Nakayama Y, Kato S, Kurasawa S, Sado T, Iwaya Y, Uehara T, Ota H.
    • Journal Title

      World Journal of Pediatrics

      Volume: 19 Issue: 3 Pages: 251-260

    • DOI

      10.1007/s12519-022-00646-x

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Colitis-associated colorectal adenocarcinomas frequently express claudin 18 isoform 2: Implications for claudin 18.2 monoclonal antibody therapy2021

    • Author(s)
      Iwaya M, Hayashi H, Nakajima T, Matsuda K, Kinugawa Y, Tobe Y, Tateishi Y, Iwaya Y, Uehara T, Ota H
    • Journal Title

      Histopathology

      Volume: Online ahead of print Issue: 2 Pages: 227-237

    • DOI

      10.1111/his.14358

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Most colitis associated carcinomas lack expression of LGR5: a preliminary study with implications for unique pathways of carcinogenesis compared to sporadic colorectal carcinoma.2021

    • Author(s)
      Iwaya M, Ota H, Nakajima T, Uehara T, Riddell R, Conner J.
    • Journal Title

      BMC Cancer

      Volume: Feb 4;21(1):119 Issue: 1

    • DOI

      10.1186/s12885-021-07835-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 炎症性腸疾患(IBD)関連腫瘍に対する組織学的アプローチについて2024

    • Author(s)
      岩谷舞
    • Organizer
      第112回日本病理学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Clinicopathological analysis of inflammatory bowel disease associated neoplasms and mutual understanding of the histological assessment of the gastrointestinal tract between Japan and Western countries2024

    • Author(s)
      岩谷舞
    • Organizer
      第112回日本病理学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Crohn’s Disease Associated Small Bowel Neoplasms Retain Cadherin 17 Expression with Occasional Co expression of Claudin 18: Implications for Tumor Targeted Immunotherapies2023

    • Author(s)
      Mai Iwaya, Makoto Kodama, Keiko Abe, Kahoko Maeda, Tomoyuki Nakajima, Takeshi Uehara, Hiroyoshi Ota
    • Organizer
      USCAP (United States and Canadian Academy of Pathology) 112th Annual Meeting
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 日本人小児消化管における相対的正常好酸球数について2022

    • Author(s)
      岩谷 舞、小林 翔太、中山 佳子、加藤 沢子、倉沢 伸吾、上原 剛、太田 浩良
    • Organizer
      第111回 病理学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 腸炎関連大腸癌は高頻度にCLDN18.2を発現する:抗CLDN18.2モノクローナル抗体治療の可能性について2022

    • Author(s)
      岩谷舞、林宏行、中嶋智之、松田和之、衣川康弘、戸部陽介、立石陽子、上原剛、太田浩良
    • Organizer
      日本病理学会 総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Loss of SATB2 expression in a subset of IBD associated neoplasm and its clinicopathologial significance2020

    • Author(s)
      Iwaya M, Ota H, Riddell R, Conner J.
    • Organizer
      日本病理学会 総会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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