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Clinical significance of RNA editing marker in patients with CRC and UC-CRC

Research Project

Project/Area Number 19K09169
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionMie University

Principal Investigator

Okugawa Yoshinaga  三重大学, 医学部附属病院, 教授 (30555545)

Co-Investigator(Kenkyū-buntansha) 問山 裕二  三重大学, 医学系研究科, 教授 (00422824)
大北 喜基  三重大学, 医学部附属病院, 講師 (20378342)
楠 正人  三重大学, 医学系研究科, 寄附講座大学教員 (50192026)
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)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥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修飾
Outline of Research at the Start

大腸組織, 糞便中, 循環cell free exosomal RNA editing解析を用いた孤大腸癌・潰瘍性大腸炎関連癌早期診断マーカーの確立 次世代シークエンサーを用いてWhole-genomeならびにRNA sequenceを行うことでadenoma-carcinoma sequence, dysplasia-carcinoma sequenceでRNA editingを来すediting site群を候補とする。さらに孤発性大腸癌・大腸腺腫, 潰瘍性大腸炎, 潰瘍性大腸炎関連癌患者, 健常人の糞便、術前血清からRNAを抽出、候補RNA editingマーカーを定量し、大腸癌患者早期診断に有効かを検証する。

Outline of Final Research Achievements

Our study showed that RNA editing was occurred tissue-specific pattern in colorectal cancer (CRC), and series of in vitro analysis revealed that RNA editing was deeply involved in disease development in CRC. In addition, intimate correlation between cancer cells and fibroblast cells via mechanism of RNA editing for CRC development in cancer microenvironments also clarified. In contrast, identified RNA editing cites did not correlated with aging factors in ulcerative colitis (UC) or UC-associated CRC, and further studies are need. Accompanied with this study, we successfully identified novel CpG site in DNA methylation level to detect patients with UC-CRC with high accuracy (AUC:0.84) via assessment of non-cancerous rectal mucosa.

Academic Significance and Societal Importance of the Research Achievements

本研究結果により、RNA後天的修飾の新たな大腸癌発癌・癌進展における機序が解明され、またエピゲノム機序を利生することで、あらたな潰瘍性大腸炎関連癌早期診断マーカー開発の一助となる可能性が考えられた。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (17 results)

All 2022 2021 2020 2019

All Journal Article (12 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 12 results,  Open Access: 4 results) Presentation (5 results)

  • [Journal Article] TPX2 is a prognostic marker and promotes cell proliferation in neuroblastoma2022

    • Author(s)
      Koike Yuhki、Yin Chengzeng、Sato Yuki、Nagano Yuka、Yamamoto Akira、Kitajima Takahito、Shimura Tadanobu、Kawamura Mikio、Matsushita Kohei、Okugawa Yoshinaga、Amano Keishiro、Otake Kohei、Okita Yoshiki、Ohi Masaki、Inoue Mikihiro、Uchida Keiichi、Hirayama Masahiro、Toiyama Yuji
    • Journal Title

      Oncology Letters

      Volume: 23 Issue: 4

    • DOI

      10.3892/ol.2022.13256

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Investigation of miRNA expression profiles using cohort samples reveals potential early detectability of colorectal cancers by serum miR-26a-5p before clinical diagnosis2022

    • Author(s)
      Hishida Asahi、Yamada Hiroya、Ando Yoshitaka、Okugawa Yoshinaga、Shiozawa Manabu、Miyagi Yohei、Daigo Yataro、Toiyama Yuji、Shirai Yumiko、Tanaka Koji、Kubo Yoko、Okada Rieko、Nagayoshi Mako、Tamura Takashi、Mori Atsuyoshi、Kondo Takaaki、Hamajima Nobuyuki、Takeuchi Kenji、Wakai Kenji
    • Journal Title

      Oncology Letters

      Volume: 23 Issue: 3 Pages: 87-87

    • DOI

      10.3892/ol.2022.13207

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cumulative C-reactive Protein in the Perioperative Period as a Novel Marker for Oncological Outcome in Patients with Colorectal Cancer Undergoing Curative Resection2021

    • Author(s)
      Fujikawa Hiroyuki、Okugawa Yoshinaga、Yamamoto Akira、Imaoka Hiroki、Shimura Tadanobu、Kitajima Takahito、Kawamura Mikio、Yasuda Hiromi、Okita Yoshiki、Yokoe Takeshi、Ohi Masaki、Toiyama Yuji
    • Journal Title

      Journal of the Anus, Rectum and Colon

      Volume: 5 Issue: 3 Pages: 281-290

    • DOI

      10.23922/jarc.2021-013

    • NAID

      130008068900

    • ISSN
      2432-3853
    • Year and Date
      2021-07-29
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preoperative heat shock protein 47 levels identify colorectal cancer patients with lymph node metastasis and poor prognosis2020

    • 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

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fusobacterium nucleatum infection correlates with two types of microsatellite alterations in colorectal cancer and triggers DNA damage2020

    • Author(s)
      Okita Yoshiki、Koi Minoru、Takeda Koki、Ross Ryan、Mukherjee Bhramar、Koeppe Erika、Stoffel Elena M.、Galanko Joseph A.、McCoy Amber N.、Keku Temitope O.、Okugawa Yoshinaga、Kitajima Takahito、Toiyama Yuji、Martens Eric、Carethers John M.
    • Journal Title

      Gut Pathogens

      Volume: 12 Issue: 1 Pages: 46-46

    • DOI

      10.1186/s13099-020-00384-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients2020

    • Author(s)
      Omura Yusuke、Toiyama Yuji、Okugawa Yoshinaga、Yin Chengzeng、Shigemori Tsunehiko、Kusunoki Kurando、Kusunoki Yukina、Ide Shozo、Shimura Tadanobu、Fujikawa Hiroyuki、Yasuda Hiromi、Hiro Junichiro、Ohi Masaki、Kusunoki Masato
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: 69 Issue: 12 Pages: 2533-2546

    • DOI

      10.1007/s00262-020-02645-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Crohn's-Like Lymphoid Reaction is Associated with Oncological Prognosis and Nutritional Status in Patients with Pathological Stage II/III Gastric Cancer.2020

    • Author(s)
      Omura Y, Toiyama Y, Okugawa Y, Yamamoto A, Yin C, Kusunoki K, Kusunoki Y, Shigemori T, Ide S, Kitajima T, Fujikawa H, Yasuda H, Hiro J, Yoshiyama S, Ohi M, Kusunoki M.
    • Journal Title

      Ann Surg Oncol

      Volume: 27 Issue: 1 Pages: 259-267

    • DOI

      10.1245/s10434-019-07709-w

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic potential of FLANC, a novel primate-specific long non-coding RNA in colorectal cancer2020

    • Author(s)
      Pichler Martin、Rodriguez-Aguayo Cristian、Nam Su Youn、Dragomir Mihnea Paul、Bayraktar Recep、Anfossi Simone、Knutsen Erik、Ivan Cristina、Fuentes-Mattei Enrique、Lee Sang Kil、Ling Hui、Catela Ivkovic Tina、Huang Guoliang、Huang Li、Okugawa Yoshinaga
    • Journal Title

      Gut

      Volume: - Issue: 10 Pages: 2019-318903

    • DOI

      10.1136/gutjnl-2019-318903

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Lymphocyte-to-C-reactive protein ratio and score are clinically feasible nutrition-inflammation markers of outcome in patients with gastric cancer2020

    • Author(s)
      Okugawa Yoshinaga、Toiyama Yuji、Yamamoto Akira、Shigemori Tsunehiko、Ichikawa Takashi、Yin Chengzeng、Suzuki Akihiro、Fujikawa Hiroyuki、Yasuda Hiromi、Hiro Junichiro、Yoshiyama Shigeyuki、Ohi Masaki、Araki Toshimitsu、McMillan Donald C.、Kusunoki Masato
    • Journal Title

      Clinical Nutrition

      Volume: 39 Issue: 4 Pages: 1209-1217

    • DOI

      10.1016/j.clnu.2019.05.009

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lymphocyte-C-reactive Protein Ratio as Promising New Marker for Predicting Surgical and Oncological Outcomes in Colorectal Cancer.2019

    • Author(s)
      Okugawa Y, Toiyama Y, Yamamoto A, Shigemori T, Ide S, Kitajima T, Fujikawa H, Yasuda H, Hiro J, Yoshiyama S, Yokoe T, Saigusa S, Tanaka K, Shirai Y, Kobayashi M, Ohi M, Araki T, McMillan DC, Miki C, Goel A, Kusunoki M
    • Journal Title

      Ann Surg. 2019 Feb 16.

      Volume: Feb Issue: 2 Pages: 16-16

    • DOI

      10.1097/sla.0000000000003239

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinical significance and biological role of L1 cell adhesion molecule in gastric cancer2019

    • 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

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genomewide Expression Profiling Identifies a Novel miRNA-Based Signature for the Detection of Peritoneal Metastasis in Patients With Gastric Cancer2019

    • Author(s)
      Shimura Tadanobu、Toden Shusuke、Kandimalla Raju、Toiyama Yuji、Okugawa Yoshinaga、Kanda Mitsuro、Baba Hideo、Kodera Yasuhiro、Kusunoki Masato、Goel Ajay
    • Journal Title

      Annals of Surgery

      Volume: - Issue: 5 Pages: 1-1

    • DOI

      10.1097/sla.0000000000003647

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 腫瘍宿主相互作用の観点に基づいた 転移組織分泌型miR-203による腫瘍誘導宿主サルコペニアの可能性の検討2019

    • Author(s)
      奥川喜永、問山裕二、藤川裕之、廣 純一郎、三澤雅子、手島信子、岩下義明、荒木俊光、三木誓雄、楠 正人
    • Organizer
      第34回日本静脈経腸栄養学会学術集会、東京
    • Related Report
      2019 Research-status Report
  • [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
    • Related Report
      2019 Research-status Report
  • [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
    • Related Report
      2019 Research-status Report
  • [Presentation] 胃癌におけるL1CAM発現解析の臨床的意義とその癌進展における機能2019

    • Author(s)
      奥川喜永、問山裕二、井出正造、北嶋貴仁、志村匡信、廣 純一郎、田中光司、楠 正人
    • Organizer
      第78回日本癌学会学術集会、京都
    • Related Report
      2019 Research-status Report
  • [Presentation] 臨床実装を視野に入れた大腸癌外科診療におけるあらたなmultiple-outcome prediction biomarkerの確立2019

    • Author(s)
      奥川喜永、問山裕二、山本 晃、大村悠介、浦谷 亮、井出正造、近藤 哲、志村匡信、安田裕美、藤川裕之、大北喜基、白井由美子、横江 毅、三枝 晋、廣 純一郎、大井正貴、荒木俊光、田中光司、三木誓雄、楠 正人
    • Organizer
      第74回日本大腸肛門病学会学術集会、東京
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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