Development of microRNA-based liquid biopsy biomarkers and anticancer treatments in digestive system cancers
Project/Area Number |
18K08690
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55020:Digestive surgery-related
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Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
Komatsu Shuhei 京都府立医科大学, 医学(系)研究科(研究院), 特任講師 (40578978)
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Co-Investigator(Kenkyū-buntansha) |
大辻 英吾 京都府立医科大学, 医学(系)研究科(研究院), 教授 (20244600)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | microRNA / リキッドバイオプシー / バイオマーカー / エキソソーム / 遊離核酸 / 核酸治療 / 抗がん剤感受性 |
Outline of Final Research Achievements |
Six candidates (miR-126, 133b, 143, 203, 338-3p, 655) of tumour suppressor miRNAs in ESCC were selected by a systematic review of NCBI database. Of these, miR-655 levels were significantly down-regulated in plasma of ESCC patients compared to healthy volunteers by test- and validation-scale analyses. Low levels of plasma miR-655 were significantly associated with lymphatic invasion, lymph node metastasis and advanced stage. Low level of plasma miR-655 was an independent risk factor of lymphatic progression and a poor prognostic factor. Overexpression of miR-655 in ESCC cells inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition. Increased plasma miR-655 levels by the subcutaneous injection significantly inhibited lymph node metastasis in mice. Low levels of miR-655 in plasma relate to lymphatic progression and poor outcomes, and the restoration of the plasma miR-655 levels might inhibit tumour and lymphatic progression in ESCC.
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Academic Significance and Societal Importance of the Research Achievements |
遺伝子発現調節に関わるmicroRNAが体液中で安定していることに注目し、血中microRNAを指標とした消化器癌の次世代型バイオマーカー探索を行ってきた。今回、食道癌患者血中で枯渇している癌抑制型miR-655に注目し、予後、リンパ節転移予測の新規バイオマーカーとして有用であり、マウス皮下投与により血中miR-655の濃度回復で、腫瘍増殖・リンパ節転移抑制の抗癌核酸治療の可能性を明らかにした。
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] TRIM37 contributes to malignant outcomes and CDDP resistance in gastric cancer.2021
Author(s)
Nishibeppu K, Komatsu S, Kiuchi J, Kishimoto T, Takashima Y, Shoda K, Arita T, Kosuga T, Konishi H, Shiozaki A, Kubota T, Okamoto K, Fujiwara H, Tsuda H, Otsuji E.
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Journal Title
Journal of Cancer
Volume: 12
Issue: 2
Pages: 316-325
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Circulating circERBB2 as a potential prognostic biomarker for gastric cancer: An investigative study.2020
Author(s)
Nanishi K, Konishi H, Shoda K, Arita T, Kosuga T, Komatsu S, Shiozaki A, Kubota T, Fujiwara H, Okamoto K, Ichikawa D, Otsuji E.
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Journal Title
Cancer Science
Volume: 111
Issue: 11
Pages: 4177-4186
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Involvement of Intracellular and Extracellular High-Mobility Group Box-1 in the Progression of Esophageal Squamous Cell Carcinoma.2020
Author(s)
Matsubara D, Konishi H, Arita T, Shoda K, Fujita Y, Ogino S, Takao K, Nanishi K, Kosuga T, Komatsu S, Shiozaki A, Fujiwara H, Okamoto K, Otsuji E.
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Journal Title
Ann Surg Oncol.
Volume: ー
Issue: 9
Pages: 3233-3244
DOI
Related Report
Peer Reviewed
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[Journal Article] ANO9 Regulated Cell Cycle in Human Esophageal Squamous Cell Carcinoma.2020
Author(s)
Katsurahara K, Shiozaki A, Kosuga T, Kudou M, Shoda K, Arita T, Konishi H, Komatsu S, Kubota T, Fujiwara H, Okamoto K, Kishimoto M, Konishi E, Marunaka Y, Otsuji E.
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Journal Title
Ann Surg Oncol.
Volume: ー
Issue: 9
Pages: 3218-3230
DOI
Related Report
Peer Reviewed
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