Establishment of tailor-made medicine for colorectal cancer arouse in serrated pathway

• Project/Area Number: 17K09476
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hiroshima University
• Principal Investigator: Shinji Tanaka 広島大学, 病院(医), 教授 (00260670)
• Co-Investigator(Kenkyū-buntansha): 卜部 祐司 広島大学, 病院(医), 助教 (10648033)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 鋸歯状腺癌 / serrated pathway / KRAS / BRAF / 早期大腸鋸歯状腺癌 / CDX2 / MSI / target-capture sequence / 早期鋸歯状腺癌 / colorectal cancer / pathogenesis / malignant potential / treatment

Outline of Final Research Achievements

The aim of this study was to clarify the characteristics for endoscopic, pathological, and molecular biological findings, and genomic alteration, associated with the poor prognosis pathway in serrated carcinogenesis. We examined the features in initial carcinogenesis development by early-stage serrated carcinomas (SACs). The results of this study found that Epithelial serration in the cancerous area indicated aggressive behavior in early-stage SACs, and Early-stage SACs were classified into three molecularly distinct subtypes with different clinicopathological and genetic characteristics.

Academic Significance and Societal Importance of the Research Achievements

Serrated pathwayは大腸癌の主な発癌経路の一つであり、予後不良な発癌経路として知られている。一方で、鋸歯状構造を有する腫瘍である鋸歯状腺腫からの大腸癌は全てserrated pathwayの様式をとって発癌するとは限らない。本研究の結果、鋸歯状腺癌は遺伝学的・病理学的に多様な発生機序を持つ疾患が混在していると考えられるため，鋸歯状腺癌の診断基準の細分化が必要となる可能性が示唆された。また，鋸歯状構造を伴う早期鋸歯状腺癌については悪性度が高いと考えられ、大腸内視鏡の治療選択の方針を選択する一つの指標となり得る可能性があると考えられた。

Research Products

• [Journal Article] Early-stage serrated adenocarcinomas are divided into several molecularly distinct subtypes. (2019)
  • Author(s): Hirano D, Urabe Y, Tanaka S, Nakamura K, Ninomiya Y, Yuge R, Hayashi R, Oka S, Kitadai Y, Shimamoto F, Arihiro K, Chayama K.
  • Journal Title: PLoS One Volume: 14 Issue: 2 Pages: e0211477-e0211477
  • DOI: 10.1371/journal.pone.0211477
• [Journal Article] Clinicopathologic and endoscopic features of early-stage colorectal serrated adenocarcinoma. (2017)
  • Author(s): Hirano D, Oka S, Tanaka S, Sumimoto K, Ninomiya Y, Tamaru Y, Shigita K, Hayashi N, Urabe Y, Kitadai Y, Shimamoto F, Arihiro K, Chayama K.
  • Journal Title: BMC Gastroenterol Volume: 17 Issue: 1 Pages: 158-158
  • DOI: 10.1186/s12876-017-0702-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Examination for genetic and clinicopathological findings for early-stage serrated adenocarcinoma using CCS classification (2018)
  • Author(s): Yuji Urabe, Shinji Tanaka, Daiki Hirano, Koki Nakamura, Yuki Ninomiya, Ryohei Hayashi, Shiro Oka, Yasuhiko Kitadai, Fumio Shimamoto, Koji Arihiro, Kazuaki Chayama
  • Organizer: The 77th Annual Meeting of the Japanese Cancer Associa
• [Presentation] 大腸早期鋸歯状腺癌における 遺伝学的分類を用いた悪性度評価の有用性 (2018)
  • Author(s): 卜部祐司、平野大樹、岡 志郎、田中信治、茶山一彰
  • Organizer: 第109回 消化器病学会 中国地方会
• [Presentation] 早期大腸鋸歯状腺癌にたいする分子生物学的検討 (2018)
  • Author(s): 卜部祐司、田中信治、茶山一影
  • Organizer: 第97回日本消化器内視鏡学会総会
• [Presentation] Malignant potential of early-stage serrated adenocarcinoma based on genetic analysis (2018)
  • Author(s): Yuji Urabe, Shinji Tanaka, Daiki Hirano, Koki Nakamura, Yuki Ninomiya, Ryo Yuge, Ryohei Hayashi, Shiro Oka, Yasuhiko Kitadai, Fumio Shimamoto, Koji Arihiro, Kazuaki Chayama
  • Organizer: UEGW2018
  • Int'l Joint Research
• [Presentation] 早期大腸鋸歯状腺癌の臨床病理学的および内視鏡的特徴. (2017)
  • Author(s): 平野大樹, 田中信治, 茶山一彰.
  • Organizer: 第103回日本消化器病学会総会
• [Presentation] 臨床病理・分子生物学検討からみた早期大腸鋸歯状腺癌の特徴. (2017)
  • Author(s): 平野大樹, 卜部祐司, 岡 志郎, 田中信治, 茶山一彰, 有廣光司.
  • Organizer: 第72回日本大腸肛門病学会学術集会