Epigenetic alternation associated with metastasis in gastrointestinal cancer

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591926
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Mie University
• Principal Investigator: YASUDA Hiromi 三重大学, 医学部附属病院, 助教 (60586767)
• Co-Investigator(Kenkyū-buntansha): TOIYAMA Yuji 三重大学, 医学部附属病院, 助教 (00422824) ; INOUE Yasuhiro 三重大学, 医学部附属病院, 講師 (20324535) ; KUSUNOKI Masato 三重大学, 医学部附属病院, 教授 (50192026)
• Project Period (FY): 2011 – 2013
• Keywords: microRNA / エピジェネティック / 消化器癌

Research Abstract

Distant metastasis tissues showed higher expression of miR-200c and miR-141 than did primary GICs, which was significantly associated with hypomethylation of the promoter region of these miRNAs. Transfection of miR-200c precursors resulted in enhanced cell proliferation but reduced invasion and migration behaviours in cancer cell lines, and caused reduced expression of putative gene targets, and resulted in epithelial-mesenchymal transition. In addition, high serum miR-200c demonstrated a significant positive correlation with lymph node metastasis, distant metastasis, and prognosis. More importantly, serum miR-200c was an independent predictor for lymph node metastasis and tumor recurrence and emerged as an independent prognostic marker.
In conclusion, miR-200c, epigenetically regulated, plays an important role in mediating EMT and metastatic behaviour in GIC. Serum miR-200c has strong potential to serve as a noninvasive biomarker for GIC prognosis and predicting metastasis.

Research Products

• [Journal Article] MicroRNAを用いた非侵襲的大腸癌診断の現状と展望 (2014)
  • Author(s): 問山裕二、奥川喜永、田中光司,井上靖浩,毛利靖彦,楠正人
  • Journal Title: 日本消化器病学会雑誌 Volume: 111(3) Pages: 482-494
• [Journal Article] Serum miR-200c is a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer (2014)
  • Author(s): Toiyama Y, Hur K, Tanaka K, Inoue Y, Kusunoki M, Boland CR, Goel A.
  • Journal Title: Ann Surg Volume: 259(4) Pages: 735-743
• [Journal Article] Increased expression of Slug and Vimentin as novel predictive biomarkers for lymph node metastasis and poor prognosis in colorectal cancer (2013)
  • Author(s): Toiyama Y, Yasuda H, Saigusa S, Tanaka K, Inoue Y, Goel A, Kusunoki M.
  • Journal Title: Carcinogenesis Volume: 34(11) Pages: 2548-2557
• [Journal Article] MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis (2013)
  • Author(s): Hur K, Toiyama Y, Takahashi M, Balaguer F, Nagasaka T, Koike J, Hemmi H, Koi M, Boland CR, Goel A.
  • Journal Title: Gut Volume: 62(9) Pages: 1315-1326
• [Presentation] 血清転移巣由来と考えられる血清microRNAsの大腸癌バイオマーカーとしての意義 (2013)
  • Author(s): 問山裕二, 井上靖浩, 川村幹雄, 川本文, 奥川喜永, 三枝晋, 廣純一郎, 田中光司, 毛利靖彦, 楠正人
  • Organizer: 日本大腸肛門病学会
  • Place of Presentation: 京王プラザ(東京都新宿区)
  • Year and Date: 20131115-1116
• [Presentation] Serum microRNA-200c and -203 as novel prognostic and metastasis predictive biomarkers in patients with colorectal cancer (2013)
  • Author(s): 問山裕二, 井上靖浩, 沖上正人, 川村幹雄, 川本文, 奥川喜永, 三枝晋, 廣純一郎, 田中光司, 毛利靖彦, Boland CR, Goel Ajay, 楠正人
  • Organizer: 日本癌学会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 20131003-1005