Searching for miRNA as a biomarker in blood colorectal cancer in blood to evaluate sensitivities against chemotherapies for colorectal cancer

2018 Fiscal Year Annual Research Report

• Project/Area Number: 15K10035
• Research Institution: Juntendo University
• Principal Investigator: 高橋 玄 順天堂大学, 医学部, 准教授 (40445549)
• Co-Investigator(Kenkyū-buntansha): 小見山 博光 順天堂大学, 医学部, 非常勤講師 (30348982) ; 加藤 俊介 順天堂大学, 医学(系)研究科(研究院), 教授 (40312657) ; 茂櫛 薫 順天堂大学, 医学(系)研究科(研究院), 非常勤講師 (60569292)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: CAGE解析 / microRNA / 抗がん剤感受性 / 治療効果判定 / 腫瘍メーカー / 大腸癌

Outline of Annual Research Achievements

本研究の目的は，大腸がんの新たな血中マーカーとしてのmicroRNA を特定することであり，臨床応用を目標とする．長らく抗がん剤治療が適さないとされてきた大腸がんであったが，近年，抗腫瘍効果の高い分子標的薬の開発により飛躍的に治療選択肢が増えた．
しかし既存のCEAや　CA19-9，p53抗体などの大腸がんマーカーでも採血のみでがんを診断することは難しく，早期診断は困難である．様々な抗がん剤を含む幅広い選択肢から最適な治療選択を行うための指標となる高い診断力を持ったマーカーの新規開発が急務となっている．報告者らは大腸癌の血中腫瘍マーカー候補としてのmicroRNAの抽出・特定を目的として，同一患者の治療適応前後のマイクロアレイ解析を行い，比較解析を行った．報告者らのグループにて既に保存してあった大腸がん患者の検体を用いることでこの比較解析が可能となった．さらに報告者らはstageごとに症例を選抜したうえでRNAを抽出し，microRNAの解析を行い，大腸癌診断マーカー候補となるmicroRNAを特定した．これらのマーカー候補遺伝子の発現の変動に着目して患者の経過を追跡し，目下，各種治療効果との対照を進めている．本研究結果から，血中microRNAの新たな診断マーカー，治療効果判定因子としての臨床応用可能性が明らかになってきている．この成果は　大腸癌の早期発見や　診断の簡便化、信頼性向上の観点から有意義であるとともに、日本の知的財産の活用という側面でも貴重である。

Research Products

• [Journal Article] Histological characteristics of eosinophilic myenteric ganglionitis: an under-recognised cause of chronic intestinal pseudo-obstruction. (2019)
  • Author(s): Akazawa Y, Hayashi T, Saito T, Niwa K, Kamiyama H, Sasahara N, Sakamoto K, Nagahara A, Yao T.
  • Journal Title: Virchows Archiv Volume: 474(3) Pages: 395-400
  • DOI: 10.1007/s00428-018-02513-5
  • Peer Reviewed
• [Journal Article] Noninvasive local correction of loop ileostomy prolapse using a stapling device for a patient in the terminal phase of malignancy. (2019)
  • Author(s): Kojima Y, Sakamoto K, Kawai M, Mizukoshi K.
  • Journal Title: Journal of Surgical Case Reports Volume: 2019(3) Pages: -
  • DOI: 10.1093/jscr/rjz050
  • Peer Reviewed / Open Access
• [Journal Article] The Association between Absence of Abdominal Pain and Mortality in Lower Intestinal Perforation in Patients with Autoimmune Rheumatic Diseases. (2019)
  • Author(s): Endo Y, Abe Y, Kawano S, Ando T, Sakamoto K, Tamura N.
  • Journal Title: BioMed Research International Volume: 2019:5381453 Pages: -
  • DOI: 10.1155/2019/5381453
  • Peer Reviewed / Open Access
• [Journal Article] DNA methylation genome-wide analysis in remnant and primary gastric cancers. (2019)
  • Author(s): Sugimoto K, Ito T, Hulbert A, Chen C, Orita H, Maeda M, Moro H, Fukagawa T, Ushijima T, Katai H, Wada R, Sato K, Sakamoto K, Yu W, Considine M, Cope L, Brock MV.
  • Journal Title: Gastric Cancer Volume: 2019 Pages: -
  • DOI: 10.1007/s10120-019-00949-5
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Endoscopic Submucosal Dissection Decreases Additional Colorectal Resection for T1 Colorectal Cancer. (2018)
  • Author(s): Tomiki Y, Kawai M, Kawano S, Ishiyama S, Sugimoto K, Takahashi M, Kojima Y, Murakami T, Ritsuno H, Shibuya T, Sakamoto N, Sakamoto K.
  • Journal Title: Medical Science Monitor Volume: 24 Pages: 6910-6917
  • DOI: 10.12659/MSM.909380
  • Peer Reviewed
• [Journal Article] Rectal neuroendocrine tumours treated using endoscopic submucosal dissection with myectomy - a video vignette. (2018)
  • Author(s): Honjo K, Kure K, Ro H, Mizukoshi K, Kawai M, Ishiyama S, Takahashi M, Tomiki Y, Sakamoto K.
  • Journal Title: Colorectal Disease Volume: 20(11) Pages: 1055-1056
  • DOI: 10.1111/codi.14418
  • Peer Reviewed
• [Journal Article] High-sensitivity detection of micrometastases generated by GFP lentivirus-transduced organoids cultured from a patient-derived colon tumor. (2018)
  • Author(s): Okazawa Y, Mizukoshi K, KoyamaY, Okubo S, Komiyama H, Kojima Y, Goto M, Habu S, Hino O,Sakamoto K, Orimo A.
  • Journal Title: Journal of Visualized Experiments Volume: (136) Pages: e57374
  • DOI: 10.3791/57374
  • Peer Reviewed
• [Journal Article] Survival benefit of lymph node dissection in surgery for colon cancer in elderly patients:multicenter propensity score-matched study in Japan. (2018)
  • Author(s): Takahashi M, Niitsu H, Sakamoto K, Hinoi T, Hattori M, Goto M, Bando H, Hazama S, Maeda K, Okita K, Horie H, Watanabe M; Japan Society of Laparoscopic Colorectal Surgery.
  • Journal Title: Asian Journal of Endoscopic Surgery Volume: 11(4) Pages: 346-354
  • DOI: 10.1111/ases.12474
  • Peer Reviewed
• [Journal Article] Surgical technique and outcomes of transabdominal preperitoneal inguinal hernia repair after radical prostatectomy: dissection between the transversalis fascia and superficial layers of preperitoneal fascia. (2018)
  • Author(s): Ohuchi M, Fukunaga M, Nagakari K, Azuma D, Kohama S, Nomoto J, Sakamoto K.
  • Journal Title: Hernia Volume: 23(1) Pages: 167-174
  • DOI: 10.1007/s10029-018-1800-6
  • Peer Reviewed
• [Journal Article] Impact of Left Colonic Artery Preservation on Anastomotic Leakage in Laparoscopic Sigmoid Resection and Anterior Resection for Sigmoid and Rectosigmoid Colon Cancer. (2018)
  • Author(s): Kato H, Munakata S, Sakamoto K, Sugimoto K, Yamamoto R, Ueda S, Tokuda S, Sakuraba S, Kushida T, Orita H, Sakurada M, Maekawa H, Sato K.
  • Journal Title: Journal of Gastrointestinal Cancer Volume: 2018 Pages: 1-5
  • DOI: 10.1007/s12029-018-0126-z
  • Peer Reviewed
• [Journal Article] DNA Methylation Research - My Experience in Johns Hopkins University. (2018)
  • Author(s): Sugimoto K, Ito T, Orita H, Fujita S, Sakamoto K, Sato K and Brock MV.
  • Journal Title: Juntendo Medical Journal Volume: 64(1) Pages: 2-10
  • DOI: 10.14789/jmj.63.264
  • Open Access / Int'l Joint Research
• [Presentation] Laparoscopic Para-Aortic Lymph Node Resection For Colorectal Cancer. (2018)
  • Author(s): Kazuhiro Sakamoto,Toshiaki Hagiwara, Hirokazu Matsuzawa, Shingo Kawano, Shinya Kawai, Koichiro Niwa, Shun Ishiyama, Kiichi Sugimoto, Hirohiko Kamiyama, Makoto Takahashi, Yutaka Kojima, Yuichi Tomiki, Tetsu Fukunaga, Yoshiaki Kajiyama, Seiji Kawasaki
  • Organizer: SAGES & CAGES 16TH WORLD CONGRESS OF ENDOSCOPIC SURGERY, Seattle, WA, USA
  • Int'l Joint Research
• [Presentation] Complete Mesocolic Excision For Transverse Colon In Our Hospital. (2018)
  • Author(s): Shun Ishiyama, Kota Amemiya, Yuki Tsuchiya, Hirokazu Matsuzawa, Shingo Kawano, Masaya Kawai, Koichiro Niwa, Kiichi Sugimoto, Hirohiko Kamiyama, Makoto Takahashi, Hiromitsu Komiyama, Yutaka Kojima, Atsushi Okuzawa, Yuichi Tomiki, Tetsu Fukunaga, Yoshiaki Kajiyama, Seiji Kawasaki, Kazuhiro Sakamoto
  • Organizer: SAGES & CAGES 16TH WORLD CONGRESS OF ENDOSCOPIC SURGERY, Seattle, WA, USA
  • Int'l Joint Research
• [Presentation] A Study On Rectum Cancer Surgery Using Needlescopic Instruments. (2018)
  • Author(s): Toshiaki Hagiwara, Yuki Tsuchiya, Shunsuke Motegi, Ryoichi Tsukamoto, Shingo Ito, Shingo Kawano, Shun Ishiyama, Kiichi Sugimoto, Makoto Takahashi, Yutaka Kojima, Tetsu Fukunaga, Yoshiaki Kajiyama, Seiji Kawasaki, Kazuhiro Sakamoto
  • Organizer: SAGES & CAGES 16TH WORLD CONGRESS OF ENDOSCOPIC SURGERY, Seattle, WA, USA
  • Int'l Joint Research
• [Presentation] Experience Of Using A Spray-Type Anti-Adhesion Barrier In Laparoscopic Surgery For Colorectal Carcinoma. (2018)
  • Author(s): Yutaka Kojima, Kazuhiro Sakamoto, Yuichi Tomiki, Michitoshi Goto, Makoto Takahashi, Hirohiko Kamiyama, Kiichi Sugimoto, Shun Ishiyama, Koichiro Niwa, Masaya Kawai, Ryoichi Tsukamoto, Shunsuke Motegi, Yurika Makino, Toshiaki Hagiwara, Seiji Kawasaki, Yoshiaki Kajiyama, Tetsu Fukunaga
  • Organizer: SAGES & CAGES 16TH WORLD CONGRESS OF ENDOSCOPIC SURGERY, Seattle, WA, USA
  • Int'l Joint Research
• [Presentation] The Feasibility Of Laparoscopic Surgery For Primary Tumor Resection In Patients With Metastatic Colorectal Cancer. (2018)
  • Author(s): Shingo Ito, Kazuhiro Sakamoto, Ryo Ohta, Yuki Tsuchiya, Hirokazu Matsuzawa, Ryoichi Tsukamoto, Shinya Munakata, Masaya Kawai, Koichiro Niwa, Shun Ishiyama, Kiichi Sugimoto, Hirohiko Kamiyama, Makoto Takahashi, Yutaka Kojima, Yuichi Tomiki
  • Organizer: SAGES & CAGES 16TH WORLD CONGRESS OF ENDOSCOPIC SURGERY, Seattle, WA, USA
  • Int'l Joint Research
• [Presentation] Survival Benefit of Lymph Node Dissection in Surgery for Colon Cancer in Elderly Patients: A Multicenter Propensity Score-matched Case-control Study in Japan (2018)
  • Author(s): M. Takahashi, H. Niitsu, K. Sakamoto, T. Hinoi, M. Hattori, M. Goto, H. Horie, M. Watanabe
  • Organizer: ASCRS 2018 Annual Meeting
  • Int'l Joint Research
• [Presentation] Short-term Outcomes of Laparoscopic Mutivisceral Resection for Locally Advanced Colon Cancer (2018)
  • Author(s): K. Sakamoto, S. Kawano, M. Kawai, K. Niwa, S. Ishiyama, K. Sugimoto, H. Kamiyama, M. Takahashi, Y. Kojima, Y. Tomiki
  • Organizer: ASCRS 2018 Annual Meeting
  • Int'l Joint Research
• [Presentation] Laparoscopic natural orifice specimen extraction using needlescopic instruments for colon cancer (2018)
  • Author(s): Kazuhiro Sakamoto, Hirokazu Matsuzawa, Yu Okazawa, Rina Takahashi, Kosuke Mizukoshi, Kiichi Sugimoto, Makoto Takahashi, Yutaka Kojima
  • Organizer: The 29th ISUCRS Biennial Congress
  • Int'l Joint Research
• [Presentation] The Significance of Plasma p14 gene DNA Methylation in Colorectal Cancer (2018)
  • Author(s): Hirokazu Matsuzawa, Kichi Sugimoto, Shun Ishiyama, Hirohiko Kamiyama, Makoto Takahashi, Yutaka Kojima, Yuichi Tomiki and Kazuhiro Sakamoto.
  • Organizer: The 29th ISUCRS Biennial Congress
  • Int'l Joint Research
• [Presentation] Prognostic Factor For Locally Advanced Rectal Cancer After Surgery Following Chemoradiotherapy: Which Factor Is More Important To Predict The Long-term Outcome? (2018)
  • Author(s): Kosuke Mizukoshi, Hirokazu Matsuzawa, Masaya Kawai, Kiichi Sugimoto, Hiromitsu Komiyama, Yutaka Kojima, Yuichi Tomiki, Kazuhiro Sakamoto.
  • Organizer: The 29th ISUCRS Biennial Congress
  • Int'l Joint Research
• [Presentation] The Combination of TAS-102 and Bevacizumab as the third line chemotherapy for metastatic colorectal cancer (TAS-CC3 Study) (2018)
  • Author(s): H. Kamiyama, Y. Yoshida, H. Yoshida, C. Kosugi, K. Ishibashi, K. Ihara, M. Takahashi, H. Kuramochi, A. Fukazawa, H. Sonoda, K. Yoshimatsu, A. Matsuda, S. Yamaguchi, H. Ishida, S. Hasegawa, T. Yamada, K. Sakamoto, K. Koda
  • Organizer: ESMO 2018 Congress
  • Int'l Joint Research
• [Presentation] 大腸癌における血漿中遊離DNAのCHFR遺伝子メチル化測定の意義(英語) (2018)
  • Author(s): 杉本 起一, 牧野 有里香, 青木 順, 岡澤 裕, 水越 幸輔, 河合 雅也, 宗像 慎也, 石山 隼, 神山 博彦, 高橋 玄, 小島 豊, 冨木 裕一, 福永 哲, 梶山 美明, 坂本 一博
  • Organizer: 第56回日本癌治療学会学術集会
• [Presentation] SLC7A1に対するモノクローナル抗体 大腸癌組織における遺伝子発現評価と,抗体の癌細胞株に対する傷害活性(Monoclonal antibodies against SLC7A1: assessment of gene expression and cytotoxicity in colorectal cancer) (2018)
  • Author(s): 深谷 緑, 小見山 博光, 杉本 起一, 神山 博彦, 益子 高, 坂本 一博
  • Organizer: 第77回日本癌学会学術総会
  • Int'l Joint Research
• [Presentation] 胃がんのゲノム・エピゲノム異常 残胃癌におけるゲノムワイドDNAメチル化解析(Genetic and epigenetic aberrations in gastric cancer DNA Methylation Genome-Wide Analysis in Remnant Gastric Cancer) (2018)
  • Author(s): 杉本 起一, 伊藤 智彰, 折田 創, 佐藤 浩一, 前田 将宏, 茂呂 浩史, 牛島 俊和, 片井 均, 和田 了, 坂本 一博, Brock Malcolm V.
  • Organizer: 第77回日本癌学会学術総会
  • Int'l Joint Research
• [Presentation] 大腸癌における循環血液中p14遺伝子DNAメチル化測定の意義 (2018)
  • Author(s): 杉本 起一, 萩原 俊昭, 神山 博彦, 高橋 玄, 小島 豊, 冨木 裕一, 福永 哲, 梶山 美明, 川崎 誠治, 坂本 一博
  • Organizer: 第73回日本消化器外科学会総会
• [Presentation] 網羅的解析を用いた新規結腸癌診断マーカーの探索 (2018)
  • Author(s): 塚本 亮一, 小見山 博光, 細谷 理樹, 河野 眞吾, 河合 雅也, 高橋 玄, 小島 豊, 冨木 裕一, 坂本 一博
  • Organizer: 第118回日本外科学会定期学術集会
• [Remarks] 順天堂大学大学院 下部消化管外科学
  • URL: https://www.juntendo.ac.jp/graduate/laboratory/labo/kabusyoukakan/