Elucidation of developmental mechanism for multiple colorectal cancers by analysis of novel colorectal cancer related genes and intestinal flora

• Project/Area Number: 17K15956
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: Aoki Hironori 札幌医科大学, 医学部, 研究員 (40749496)
• Research Collaborator: SUZUKI Hiromu ; YAMAMOTO Eiichiro ; YAMANO Hiro-o ; SUGAI Tamotsu
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 多発大腸がん / 腸内細菌叢 / 大腸癌

Outline of Final Research Achievements

We performed whole-exon sequencing and whole-transcriptome analysis of the tumor area of multiple colorectal cancer cases and background normal mucous membranes for endoscopically collected colorectal tumors.
Gene A was identified as a mutation common to the cancerous part of multiple colorectal cancer cases and background normal colorectal mucosa from whole exon sequence analysis. When the single nucleotide polymorphism of the identified gene A was examined using a pyrosequencer, it was found to show extremely high correlation with superficial tumors and multiple colorectal cancers. In addition, it was found from whole transcriptome analysis that 272 genes whose expression was different in normal colon mucosa were extracted depending on the genotype of gene A, and gene ontology analysis showed high correlation with immune system and immune response.

Academic Significance and Societal Importance of the Research Achievements

表面型大腸腫瘍は一般的なadenoma-carcinomaシークエンスとは異なる分子進化を辿る可能性が指摘されているが、その詳細は明らかではない。SNPデータベースから、表面型腫瘍および多発大腸がんと相関する遺伝子Aの遺伝子型はアジア人に特有であり、欧米人には稀とされている。本研究の成果は日本人の多発表面型ポリポーシスの分子基盤解明に影響を及ぼすと考えられ、我が国のがん医療にフィードバックしうると考える。

Research Products

• [Journal Article] Subtypes of the Type II Pit Pattern Reflect Distinct Molecular Subclasses in the Serrated Neoplastic Pathway. (2018)
  • Author(s): Aoki H, Yamamoto E, Yamano HO, Sugai T, Kimura T, Tanaka Y, Matsushita HO, Yoshikawa K, Takagi R, Harada E, Nakaoka M, Yoshida Y, Harada T, Sudo G, Eizuka M, Yorozu A, Kitajima H, Niinuma T, Kai M, Nojima M, Suzuki H, Nakase H.
  • Journal Title: Dig Dis Sci. Volume: 15 Issue: 7 Pages: 1920-1928
  • DOI: 10.1007/s10620-018-5016-5
  • Peer Reviewed / Open Access
• [Journal Article] Surface microstructures are associated with mutational intratumoral heterogeneity in colorectal tumors (2018)
  • Author(s): Harada T、Yamamoto E、Yamano HO、Aoki H、Matsushita HO、Yoshikawa K、Takagi R、Harada E、Tanaka Y、Yoshida Y、Eizuka M、Yorozu A、Sudo G、Kitajima H、Niinuma T、Kai M、Sasaki Y、Tokino Takashi、Sugai T、Nakase H、Suzuki H
  • Journal Title: Journal of Gastroenterology Volume: 53 Issue: 12 Pages: 1241-1252
  • DOI: 10.1007/s00535-018-1481-z
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer. (2017)
  • Author(s): Aoki H, Yamamoto E, Takasawa A, Niinuma T, Yamano HO, Harada T, Matsushita HO, Yoshikawa K, Takagi R, Harada E, Tanaka Y, Yoshida Y, Aoyama T, Eizuka M, Yorozu A, Kitajima H, Kai M, Sawada N, Sugai T, Nakase H, Suzuki H.
  • Journal Title: Oncotarget. Volume: 9 Issue: 4 Pages: 4707-4721
  • DOI: 10.18632/oncotarget.23523
  • Peer Reviewed / Open Access
• [Presentation] SMOC1のエピジェネティックなサイレンシングは大腸鋸歯状腺腫の発育進展に関与する (2018)
  • Author(s): 青木敬則, 山本英一郎, 高澤啓, 新沼猛, 山野泰穂, 萬顕, 北嶋洋志, 甲斐正広, 澤田典均, 仲瀬裕志, 菅井有, 鈴木拓
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] Endoscopic and molecular characteristics during the development of traditional serrated adenoma (2018)
  • Author(s): Hironori Aoki, Eiichiro Yamamoto, Hiro-o Yamano, Hiro-o Matsushita, Kenjiro Yoshikawa, Eiji Harada, Yoshihito Tanaka, Taku Harada, Tamotsu Sugai and Hiromu Suzuki
  • Organizer: 26th UEG Week
  • Int'l Joint Research
• [Presentation] SMOC1のエピジェネティックなサイレンシングは大腸鋸歯状腺腫の発育進展に関連する (2017)
  • Author(s): 青木敬則, 山本英一郎, 高澤啓, 新沼猛, 山野泰穂, 原田拓, 萬顕, 北嶋洋志, 甲斐正広, 澤田典均, 仲瀬裕志, 菅井有, 鈴木拓
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] Epigenetic silencing of SMOC1 is associated with development of colorectal traditional serrated adenomas (2017)
  • Author(s): Hironori Aoki, Eiichiro Yamamoto, Akira Takasawa, Takeshi Niinuma, Hiro-o Yamano, Hiro-o Matsushita, Taku Harada, Tamotsu Sugai, Hiroshi Nakase and Hiromu Suzuki
  • Organizer: 25th UEG Week
  • Int'l Joint Research
• [Presentation] Endoscopic and molecular characteristics in colorectal serrated lesions represent subclasses of the serrated neoplasia pathway (2017)
  • Author(s): Hironori Aoki, Eiichiro Yamamoto, Hiro-o Yamano, Hiro-o Matsushita, Kenjiro Yoshikawa, Ryo Takagi, Eiji Harada, Yoshihito Tanaka, Taku Harada, Tamotsu Sugai, Hiroshi Nakase and Hiromu Suzuki
  • Organizer: 25th UEG Week
  • Int'l Joint Research