Development of novel screening method using exosomal miRNAs in CRC.

• Project/Area Number: 16K15612
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Mie University
• Principal Investigator: Kusunoki Masato 三重大学, 医学系研究科, 教授 (50192026)
• Co-Investigator(Kenkyū-buntansha): 問山 裕二 三重大学, 医学部付属病院, 講師 (00422824) ; 田中 光司 三重大学, 医学系研究科, 客員准教授 (10345986) ; 井上 靖浩 三重大学, 医学系研究科, 客員准教授 (20324535)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 大腸癌 / エキソソーム / microRNA / 包埋遺伝子情報 / バイオマーカー / エクソソーム / トランスレーショナルリサーチ

Outline of Final Research Achievements

In this study, we focused on exosome-expressed protein, including Glypican-1, to develop novel screening method using exosomal miRNAs in CRC patients. During the series of this project, we successfully find several novel findings. As first, we directly compared between exosomal and serum-derived miRNAs in adenoma patients, and showed that diagnostic potential of serum-derived miRNAs are superior to exosomal miRNAs in these patients. Second, we performed comprehensive protein profiling using exosomal protein from CRC cells and normal cells, and identified canditate proteins to specifically expressed in CRC tissues. Finally, we demonstrated that serum miR-1290 could be used as a diagnostic and prognotic biomarker in CRC patients.

Research Products

• [Journal Article] MiR-139-5p as a novel serum biomarker for recurrence and metastasis in colorectal cancer. (2017)
  • Author(s): Miyoshi J, Toden S, Yoshida K, Toiyama Y, Alberts SR, Kusunoki M, Sinicrope FA, Goel A.
  • Journal Title: Sci Rep. Volume: - Issue: 1 Pages: 43393-43393
  • DOI: 10.1038/srep43393
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] CCAT1 and CCAT2 long noncoding RNAs, located within the 8q.24.21 ‘gene desert’, serve as important prognostic biomarkers in colorectal cancer (2017)
  • Author(s): Ozawa T, Matsuyama T, Toiyama Y, Takahashi N, Ishikawa T, Uetake H, Yamada Y, Kusunoki M, Calin G, Goel A.
  • Journal Title: Annals of Oncology. Volume: 28 Issue: 8 Pages: 1882-1888
  • DOI: 10.1093/annonc/mdx248
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Panel of Methylated MicroRNA Biomarkers for Identifying High-Risk Patients With Ulcerative Colitis-Associated Colorectal Cancer. (2017)
  • Author(s): Toiyama Y, Okugawa Y, Tanaka K, Araki T, Uchida K, Hishida A, Uchino M, Ikeuchi H, Hirota S, Kusunoki M, Boland CR, Goel A.
  • Journal Title: Gastroenterology. Volume: 153 Issue: 6 Pages: 1634-1646
  • DOI: 10.1053/j.gastro.2017.08.037
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] FOXD3 Regulates CSC Marker, DCLK1-S, and Invasive Potential: Prognostic Implications in Colon Cancer. (2017)
  • Author(s): Sarkar S, O'Connell MR, Okugawa Y, Lee BS, Toiyama Y, Kusunoki M, Daboval RD, Goel A, Singh P.
  • Journal Title: Mol Cancer Res. Volume: 15 Pages: 1678-1691
  • Peer Reviewed
• [Journal Article] Diagnostic Potential of Cell-Free and Exosomal MicroRNAs in the Identification of Patients with High-Risk Colorectal Adenomas. (2016)
  • Author(s): Uratani R, Toiyama Y, Kitajima T, Kawamura M, Hiro J, Kobayashi M, Tanaka K, Inoue Y, Mohri Y, Mori T, Kato T, Goel A, Kusunoki M.
  • Journal Title: PLoS One. Volume: 11(10) Issue: 10 Pages: e0160722-e0160722
  • DOI: 10.1371/journal.pone.0160722
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer (2016)
  • Author(s): Imaoka H, Toiyama Y, Fujikawa H, Hiro J, Saigusa S, Tanaka K, Inoue Y, Mohri Y, Mori T, Kato T, Toden S, Goel A, Kusunoki M.
  • Journal Title: Ann Oncol. Volume: 27(10） Issue: 10 Pages: 1879-1886
  • DOI: 10.1093/annonc/mdw279
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 大腸腺腫患者における非侵襲的診断マーカーとしての血清およびエクソソームmicro RNA の比較検討. (2017)
  • Author(s): 北嶋貴仁、問山裕二、志村匡信、今岡裕基、沖上正人、安田裕美、奥川喜永、大北喜基、吉山繁幸、廣純一郎、三枝晋、井上幹大、小林美奈子、大井正貴、荒木俊光、田中光司、 井上靖浩、内田恵一、毛利靖彦、楠 正人
  • Organizer: 第87回大腸癌研究会
• [Presentation] ：miRNAsメチル化マーカーパネルを用いた潰瘍性大腸炎患者の癌化リスク診断 (2017)
  • Author(s): 問山裕二、奥川 喜永、荒木 俊光、小林 美奈子、大北 喜基、田中 光司、井上 靖浩、内田 恵一、毛利 靖彦、楠 正人
  • Organizer: 第72回日本消化器外科学会総会
• [Presentation] 消化管悪性腫瘍におけるBDNF/TrkB axisの腹膜播種進展における機序解明と，治療標的としての可能性. (2017)
  • Author(s): 奥川喜永、問山裕二、楠 正人
  • Organizer: 第15回日本消化器外科学会大会
• [Presentation] The clinical significance of epigenetic microRNA-137 silencing in patients with ulcerative colitis. (2017)
  • Author(s): Toiyama Y, Okugawa Y , Hur K ,Tanaka K, Araki T, Uchida K , Uchino M , Ikeuchi H , Hirota S , Kusunoki M ,Boland CR, Goel A
  • Organizer: AACR Annual Meeting , Washington,D.C., USA, April 4,2017
  • Int'l Joint Research
• [Presentation] Preoperative evaluation of heat shock protein 47 expression to identify patients with colorectal cancer with lymph node metastasis and poor prognosis. (2017)
  • Author(s): Mori K, Toiyama Y, Okugawa Y, Ichikawa T, Nagano Y, Oki S, Imaoka H, Okigami M, Fujikawa H, Hiro J, Saigusa S, Kobayashi M, Inoue Y, Mohri Y, Kusunoki M
  • Organizer: 2017 Gastrointestinal Cancers Symposium San Francisco, California, USA, Jan 21, 2017
  • Int'l Joint Research
• [Presentation] Diagnostic potential of serum and exosomal microRNAs for patients with pre-malignant lesions of colorectal cancer:Detection of adenoma. (2016)
  • Author(s): Uratani R,Toiyama Y,Kitajima T,Fujikawa H,Hiro J,Kobayashi M,Tanaka K,Inoue Y,Mohri Y,Mori T,Kato T,Goel A,Kusunoki M
  • Organizer: AACR2016
  • Place of Presentation: New Orleans(USA)
  • Year and Date: 2016-04-18
  • Int'l Joint Research
• [Presentation] Circulating microRNA-1290 as a novel diagnostic biomarker in human colorectal cancer (2016)
  • Author(s): Toiyama Y,Imaoka H,Fujikawa H,Hiro J,Saigusa S,Tanaka K,Inoue Y,Mohri Y,Mori K,Kato T,Goel A,Kusunoki M
  • Organizer: AACR2016
  • Place of Presentation: New Orleans(USA)
  • Year and Date: 2016-04-18
  • Int'l Joint Research