Clinical burden of RNA methylation as a diagnostic and predictive marker for colitis-associated cancer.

• Project/Area Number: 18K08591
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Mie University
• Principal Investigator: Inoue Yasuhiro 三重大学, 医学系研究科, 客員准教授 (20324535)
• Co-Investigator(Kenkyū-buntansha): 問山 裕二 三重大学, 医学系研究科, 教授 (00422824) ; 奥川 喜永 三重大学, 医学部附属病院, 講師 (30555545) ; 藤川 裕之 三重大学, 医学部附属病院, 助教 (40616091) ; 荒木 俊光 三重大学, 医学系研究科, リサーチアソシエイト (70343217) ; 楠 正人 三重大学, 医学系研究科, 寄附講座大学教員 (50192026)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 潰瘍性大腸炎 / 大腸癌 / メチル化 / RNAメチル化 / 大腸がん / 潰瘍性大腸炎関連癌 / バイオマーカー

Outline of Final Research Achievements

In this study, we conducted comprehensive methylation analysis using surgical specimens from sporadic colorectal cancer or ulcerative colitis-associated CRC, and successfully identified cancer-specific hypermethylated CpG site. Furthermore, we validated this CpG site using pyrosequencing, and showed that quantification of methylation levels using non-neoplastic rectal mucosa could identify high-risk UC patients for CRC.

Academic Significance and Societal Importance of the Research Achievements

今回、潰瘍性大腸炎における様々な部位の大腸粘膜におけるメチル化の程度を明らかにし、さらに内視鏡検査にて簡便に評価可能かつ肛門鏡で生検可能な直腸粘膜を用い、そのメチル化のField effect/cancerizationを用いた大腸全体の癌化の状況を判別する概念を確立することはこれまでにない新しいアプローチとなる。

Research Products

• [Journal Article] Preoperative heat shock protein 47 levels identify colorectal cancer patients with lymph node metastasis and poor prognosis (2020)
  • Author(s): Mori Koichiro、Toiyama Yuji、Okugawa Yoshinaga、Ichikawa Takashi、Nagano Yuka、Oki Satoshi、Shimura Tadanobu、Fujikawa Hiroyuki、Hiro Junichiro、Kobayash Minako、Araki Toshimitsu、Inoue Yasuhiro、Mohri Yasuhiko、Kusunoki Masato
  • Journal Title: Oncology Letters Volume: 20 Issue: 6 Pages: 333-333
  • DOI: 10.3892/ol.2020.12196
  • Peer Reviewed
• [Journal Article] Phase I study of preoperative chemoradiotherapy with sequential oxaliplatin and irinotecan with S-1 for locally advanced rectal cancer (2019)
  • Author(s): Fujikawa Hiroyuki、Toiyama Yuji、Inoue Yasuhiro、Omura Yusuke、Ide Shozo、Kitajima Takahito、Yasuda Hiromi、Okugawa Yoshinaga、Okita Yoshiki、Yoshiyama Shigeyuki、Hiro Junichiro、Kobayashi Minako、Ohi Masaki、Araki Toshimitsu、Kusunoki Masato
  • Journal Title: Oncology Letters Volume: 17(4) Pages: 3930-3936
  • DOI: 10.3892/ol.2019.10028
  • Peer Reviewed
• [Journal Article] Genetic influence of cytokine polymorphisms on the clinical outcome of Japanese gastrointestinal cancer patients in palliative care (2019)
  • Author(s): Hishida Asahi、Okugawa Yoshinaga、Morimoto Yuhki、Shirai Yumiko、Okamoto Kyoko、Momokita Sachiko、Ogawa Aki、Tanaka Koji、Nishikawa Ryutaro、Toiyama Yuji、Inoue Yasuhiro、Sakurai Hiroyuki、Urata Hisashi、Tanaka Motoyoshi、McMillan Donald、Miki Chikao
  • Journal Title: Oncology Letters Volume: 17(1) Pages: 623-629
  • DOI: 10.3892/ol.2018.9614
• [Journal Article] Clinical significance and biological role of L1 cell adhesion molecule in gastric cancer (2019)
  • Author(s): Ichikawa Takashi、Okugawa Yoshinaga、Toiyama Yuji、Tanaka Koji、Yin Chengzeng、Kitajima Takahito、Kondo Satoru、Shimura Tadanobu、Ohi Masaki、Araki Toshimitsu、Kusunoki Masato
  • Journal Title: British Journal of Cancer Volume: 121 Issue: 12 Pages: 1058-1068
  • DOI: 10.1038/s41416-019-0646-8
  • Peer Reviewed / Open Access
• [Journal Article] Activation of AZIN1 RNA editing is a novel mechanism that promotes invasive potential of cancer-associated fibroblasts in colorectal cancer (2019)
  • Author(s): Takeda S, Shigeyasu K, Okugawa Y, Yoshida K, Mori Y, Yano S, Noma K, Umeda Y, Kondo Y, Kishimoto H, Teraishi F, Nagasaka T, Tazawa H, Kagawa S, Fujiwara T, Goel A.
  • Journal Title: Cancer Lett Volume: 444 Pages: 127-135
  • DOI: 10.1016/j.canlet.2018.12.009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 網羅的メチル化解析から抽出したOPLAHメチル化異常の潰瘍性大腸炎における臨床的意義 (2019)
  • Author(s): 問山裕二、山本 晃、奥川喜永、楠 蔵人、楠 由希奈、大村悠介、市川 崇、井出正造、志村匡信、北嶋貴仁、藤川裕之、安田裕美、大北喜基、横江 毅、廣 純一郎、大井正貴、荒木俊光、内田恵一、楠 正人
  • Organizer: 第74回日本大腸肛門病学会学術集会、東京
• [Presentation] 網羅的DNAメチル化解析から抽出した潰瘍性大腸炎合併大腸癌診断マーカー (2019)
  • Author(s): 問山裕二、山本 晃、奥川喜永、楠 蔵人、大村悠介、藤川裕之、大北喜基、廣 純一郎、大井正貴、内田恵一、楠 正人
  • Organizer: 第74回日本消化器外科学会総会、東京