Establishment of the method to identify the ulcerative colitis patients with high risk of colorectal cancer
| Project/Area Number |
17K10628
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Mie University |
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Principal Investigator |
Toiyama Yuji 三重大学, 医学系研究科, 准教授 (00422824)
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| Co-Investigator(Kenkyū-buntansha) |
井上 靖浩 三重大学, 医学系研究科, 客員准教授 (20324535)
楠 正人 三重大学, 医学系研究科, 教授 (50192026)
荒木 俊光 三重大学, 医学系研究科, 准教授 (70343217)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 潰瘍性大腸炎 / 大腸癌 / DNAメチル化 / 癌化 / バイオマーカー |
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| Outline of Final Research Achievements |
We conducted comprehensive methylation array to identify novel DNA methylation markers for predicting the risk of neoplasia in UC patients.We collected 23 rectal samples from UC patients with CRC and 24 rectal samples from UC patients in cohort1. We also collected 8 rectal samples from UC patients with CRC and 24 rectal samples from UC patients without CRC in cohort 2.
We identified 486 differentially methylated regions (DMRs) with absolute delta beta-value > 0.1 in rectal mucosal tissues of UC patients with CAC compared with that without neoplasia. Next, pathway enrichment analysis was performed to select coordinately methylated DMRs, and 180 DMRs were extracted. Finally, optimal 11 DMRs were selected by the Elastic Net classification algorithm. In the ROC analysis for cohort 1, the AUC was 0.96. For cohort 2, the AUC was 0.81. We identified 11 DMRs for identifying UC patients with high risk of developing CAC.
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| Academic Significance and Societal Importance of the Research Achievements |
同一臓器内に同時・異時性多発癌が生じやすくする”Field cancerization”の概念がDNAメチル化の分野で提唱されており、その変化を評価することにより、発癌の素地を検出可能と考え、本研究へ応用した。直腸粘膜の採取で、全大腸のどの部位にも大腸癌が発生しているリスク評価ができる結果であり、この結果を臨床応用可能であれば、潰瘍性大腸炎患者の癌化診断に対して、年に一度繰り返し行われる大腸内視鏡検査やそれに伴う多数の生検による侵襲的負担の軽減、癌化の見落としによる不幸な予後の回避、さらには高齢化による高騰する医療費の削減にも効果が発揮されるものであると考えている。
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Inflammation-Associated Microsatellite Alterations Caused by MSH3 Dysfunction Are Prevalent in Ulcerative Colitis and Increase With Neoplastic Advancement.2019
Author(s)
Munakata K, Koi M, Kitajima T, Tseng-Rogenski S, Uemura M, Matsuno H, Kawai K, Sekido Y, Mizushima T, Toiyama Y, Yamada T, Mano M, Mita E, Kusunoki M, Mori M, Carethers JM.
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Journal Title
Clin Transl Gastroenterol.
Volume: 10
Issue: 12
Pages: e00105-e00105
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Comprehensive analysis identifying aberrant DNA methylation in rectal mucosa from ulcerative colitis patients with neoplasia.2018
Author(s)
Toiyama Y, Okugawa Y, Kondo S, Okita Y, Araki T, Kusunoki K, Uchino M, Ikeuchi H, Hirota S, Mitsui A, Takehana K, Umezawa T, Kusunoki M.
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Journal Title
Oncotarget.
Volume: 4
Issue: 69
Pages: 33149-33159
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Gastroenterology.
Volume: 153
Issue: 6
Pages: 1634-1646
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[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 由紀奈, 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
日本大腸肛門病学会
Related Report
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