Identification of molecules involved in the carcinogenesis of serrated lesions of the colon and their clinical application.

• Project/Area Number: 19K17437
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kumamoto University
• Principal Investigator: Shono Takashi 熊本大学, 大学院生命科学研究部(医), 特定研究員 (40632667)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2021: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: SSA/P / マイクロRNA / 発がんマーカー / Serrated pathway / microRNA / SSAP / miRNA / マルチオミクス / マルチオミクス解析 / 大腸鋸歯状病変

Outline of Research at the Start

本研究では内視鏡的に切除された鋸歯状病変(Sessile Serrated Adenoma/Polyp: SSAP)を対象に、プロテオーム解析とトランスクリプトーム解析とを統合的に解析し、SSAP由来の発癌機構の解明を目的とする。
具体的には、右側結腸におけるSSAP、SSAP由来癌、正常粘膜をそれぞれ個別に回収し、網羅的解析を行い、発癌に関与する分子群を絞りこむ。また先行研究で得られたmiRNAの発現解析結果を統合し、SSAPが癌へ進展する分子基盤となる責任分子とそれを制御するmiRNAを同定する。最終的には、生体試料を用いてSSAPの早期診断法や治療戦略を構築する。

Outline of Final Research Achievements

Based on miRNA analysis of endoscopically resected tissue from colorectal cancer arising from sessile serrated adenoma/polyp (SSAP) in the proximal colon, we identified six pathways, including the TGF-beta signaling pathway, as common pathways associated with the cancerous region.
In addition, endoscopically resected tissue samples of polyp-like adenoma and Laterally spreading tumor (LST) of the colon were separated into normal and tumor portions, then their miRNA and mRNA expression analysis identified three types of miRNAs whose expression varied between the two portions. Experiments using cultured cells derived from colorectal cancer suggested that one of the identified miRNAs was associated with the growth and progression of colon cancer cells.

Academic Significance and Societal Importance of the Research Achievements

大腸癌の原因のほとんどは腺腫が原因と考えられてきたが、近年、鋸歯状病変(SSAP)も大腸癌の前駆病変であることが明らかになってきた。しかし、その分子基盤は不明であった。本研究にて同定したmiRNAはSSAPが癌へと進展するserrated pathwayの分子生物学的解明の一翼を担う可能性があり、さらにSSAPより発生する増殖の早い大腸癌に対して、新しい診断方法や治療戦略の臨床応用を展開するための基盤となり得る。

Research Products

• [Journal Article] Factors Predicting Difficult Biliary Cannulation during Endoscopic Retrograde Cholangiopancreatography for Common Bile Duct Stones (2022)
  • Author(s): Saito Hirokazu、Kadono Yoshihiro、Shono Takashi、Kamikawa Kentaro、Urata Atsushi、Nasu Jiro、Imamura Haruo、Matsushita Ikuo、Kakuma Tatsuyuki、Tada Shuji
  • Journal Title: Clinical Endoscopy Volume: 55 Issue: 2 Pages: 263-269
  • DOI: 10.5946/ce.2021.153
• [Journal Article] Low Detection Rates of Bile Duct Stones During Endoscopic Treatment for Highly Suspected Bile Duct Stones with No Imaging Evidence of Stones (2022)
  • Author(s): Saito Hirokazu、Iwasaki Hajime、Itoshima Hisashi、Kadono Yoshihiro、Shono Takashi、Kamikawa Kentaro、Urata Atsushi、Nasu Jiro、Uehara Masayoshi、Matsushita Ikuo、Kakuma Tatsuyuki、Tada Shuji
  • Journal Title: Digestive Diseases and Sciences Volume: 68 Issue: 5 Pages: 2061-2068
  • DOI: 10.1007/s10620-022-07773-5
• [Journal Article] Endoscopic retrograde cholangiopancreatography for bile duct stones in patients with a performance status score of 3 or 4 (2022)
  • Author(s): Saito Hirokazu、Kadono Yoshihiro、Shono Takashi、Kamikawa Kentaro、Urata Atsushi、Nasu Jiro、Imamura Haruo、Matsushita Ikuo、Kakuma Tatsuyuki、Tada Shuji
  • Journal Title: World Journal of Gastrointestinal Endoscopy Volume: 14 Issue: 4 Pages: 215-225
  • DOI: 10.4253/wjge.v14.i4.215
• [Journal Article] Clinical impact of gastrointestinal endoscopy on the early detection of pharyngeal squamous cell carcinoma: A retrospective cohort study. (2021)
  • Author(s): Miyamoto H, Naoe H, Morinaga J, Sakisaka K, Tayama S, Matsuno K, Gushima R, Tateyama M, Shono T, Imuta M, Miyamaru S, Murakami D, Orita Y and Tanaka Y.
  • Journal Title: World J Gastrointestinal Endoscopy Volume: 13 Issue: 10 Pages: 491-501
  • DOI: 10.4253/wjge.v13.i10.491
  • Peer Reviewed / Open Access
• [Journal Article] Usefulness of an artificial intelligence system for the detection of esophageal squamous cell carcinoma evaluated with videos simulating overlooking situation (2021)
  • Author(s): Waki K、Ishihara R、Kato Y、Shoji A、Inoue T、Matsueda K、Miyake M、Shimamoto Y、Fukuda H、Matsuura N、Ono Y、Yao K、Hashimoto S、Terai S、Ohmori M、Tanaka K、Kato M、Shono T、Miyamoto H、Tanaka Y、Tada T
  • Journal Title: Digestive Endoscopy Volume: 33 Issue: 7 Pages: 1101-1109
  • DOI: 10.1111/den.13934
  • Peer Reviewed
• [Journal Article] Disease-Based Risk Stratification of Postendoscopic Retrograde Cholangiopancreatography Pancreatitis for Common Bile Duct Stones (2021)
  • Author(s): Saito Hirokazu、Sakaguchi Masafumi、Kadono Yoshihiro、Shono Takashi、Kamikawa Kentaro、Urata Atsushi、Nasu Jiro、Imamura Haruo、Matsushita Ikuo、Kakuma Tatsuyuki、Tada Shuji
  • Journal Title: Digestive Diseases and Sciences Volume: - Issue: 1 Pages: 305-314
  • DOI: 10.1007/s10620-021-06825-6
  • Peer Reviewed
• [Journal Article] Dual-layer spectral detector computed tomography versus magnetic resonance cholangiopancreatography for biliary stones (2020)
  • Author(s): Saito Hirokazu、Iwagoi Yuki、Noda Kana、Atsuji Shutaro、Takaoka Hiroko、Kajihara Hiroo、Shono Takashi、Nasu Jiro、Obara Hitoshi、Kakuma Tatsuyuki、Tada Shuji、Morishita Shoji、Matsushita Ikuo、Katahira Kazuhiro
  • Journal Title: European Journal of Gastroenterology & Hepatology Volume: 33 Issue: 1 Pages: 32-39
  • DOI: 10.1097/meg.0000000000001832
  • Peer Reviewed
• [Journal Article] Prognostic and clinical impact of PD-L2 and PD-L1 expression in a cohort of 437 oesophageal cancers (2020)
  • Author(s): Okadome Kazuo、Baba Yoshifumi、Nomoto Daichi、Yagi Taisuke、Kalikawe Rebecca、Harada Kazuto、Hiyoshi Yukiharu、Nagai Yohei、Ishimoto Takatsugu、Iwatsuki Masaaki、Iwagami Shiro、Miyamoto Yuji、Yoshida Naoya、Watanabe Masayuki、Komohara Yoshihiro、Shono Takashi、Sasaki Yutaka、Baba Hideo
  • Journal Title: British Journal of Cancer Volume: - Issue: 10 Pages: 1535-1543
  • DOI: 10.1038/s41416-020-0811-0
  • Peer Reviewed
• [Journal Article] Laparoscopic and Endoscopic Cooperative Surgery for Rectal GI Stromal Tumor (2020)
  • Author(s): Hiyoshi Yukiharu、Yamasaki Akira、Shono Takashi、Miyamoto Yuji、Eto Kojiro、Nagai Yohei、Iwatsuki Masaaki、Iwagami Shiro、Baba Yoshifumi、Yoshida Naoya、Baba Hideo
  • Journal Title: Diseases of the Colon & Rectum Volume: 63 Issue: 1 Pages: 116-116
  • DOI: 10.1097/dcr.0000000000001514
  • Peer Reviewed
• [Journal Article] Detection of hypopharyngeal cancer (Tis, T1 and T2) by ENT physicians vs gastrointestinal endoscopists (2020)
  • Author(s): Kumai Yoshihiko、Shono Takashi、Waki Kotaro、Murakami Daizo、Miyamaru Satoru、Sasaki Yutaka、Orita Yorihisa
  • Journal Title: Auris Nasus Larynx Volume: 47 Issue: 1 Pages: 135-140
  • DOI: 10.1016/j.anl.2019.05.007
  • Peer Reviewed / Open Access
• [Journal Article] Cytotoxin-Associated Gene-A-Seropositivity and Interleukin-1 Polymorphisms Influence Adverse Cardiovascular Events. (2020)
  • Author(s): Tabata N, SuetaD, Arima Y, Okamoto K, Shono T, Hanatani S, Takashio S, Oniki K, Saruwatari J, Sakamoto K, Kaikita K, Sinning JM, Werner K, Nickenig G, Sasaki Y, Fukui T, and Tsujita K.
  • Journal Title: IJC Heart & Vasculature Volume: - Pages: 100498-100498
  • DOI: 10.1016/j.ijcha.2020.100498
  • Peer Reviewed / Open Access
• [Journal Article] Risk stratification of advanced colorectal neoplasia after baseline colonoscopy: Cohort study of 17 Japanese community practices (2019)
  • Author(s): Shono Takashi、Oyama Shinichiro、Oda Yasushi、Yokomine Kazunori、Murakami Yoshitaka、Miyamoto Hideaki、Tanaka Motohiko、Naoe Hideaki、Sasaki Yutaka、the Kumamoto Colon Cancer Study Group
  • Journal Title: Digestive Endoscopy Volume: 32 Issue: 1 Pages: 106-113
  • DOI: 10.1111/den.13516
  • Peer Reviewed / Open Access
• [Journal Article] Continuous Anticoagulation and Cold Snare Polypectomy Versus Heparin Bridging and Hot Snare Polypectomy in Patients on Anticoagulants With Subcentimeter Polyps (2019)
  • Author(s): Takeuchi Yoji, Shono Takashi, Inoue T, Ohda Y, Kobayashi N, Tanuma T, Sato R, Sakamoto T, Harada N, Chino A, Ishikawa H, Nojima M, Uraoka T et al. for the Madowazu Study Group
  • Journal Title: Annals of Internal Medicine Volume: 171 Issue: 4 Pages: 229-229
  • DOI: 10.7326/m19-0026
  • Peer Reviewed / Open Access