2023 Fiscal Year Final Research Report
Development of a Postoperative Early Recurrence Diagnosis System for Colorectal Cancer ctDNA and the Clinical Significance of the Evolutionary Phylogeny of Recurrence
| Project/Area Number |
21K07179
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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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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
三森 功士 九州大学, 大学病院, 教授 (50322748)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | メチル化 / MRD / 補助化学療法 / ctDNA / digitalPCR / 転移ニッチ / CAF |
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| Outline of Final Research Achievements |
We analyzed methylation array data and selected three markers, GPC6, FGD5, and MSC, that meet the following five criteria: (1) colon cancer-specific, (2) cancer cell-specific, (3) not expressed in normal tissues, (4) inverse correlation between expression of the target transcript and methylation β-value, (5) independent poor prognostic factor. After extracting ctDNA, we used a detection system based on digital PCR to analyze and clarify its clinical significance. Furthermore, using the machine learning pipeline DeepCOLOR on single-cell data, we identified that GPC6, which is highly methylated and lowly expressed, co-localizes and communicates with CAF cells. As a result, GPC6, which is derived from CAF and secretes CCL2, contributes to metastatic colony formation.
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| Free Research Field |
外科
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| Academic Significance and Societal Importance of the Research Achievements |
大腸がんの罹患率・死亡率は世界でも本邦でも依然として高く社会問題の一つである。特に根治切除可能なstage IIまたはIII進行大腸がんは、治療の感受性(抵抗性)評価、再発の早期診断を実現する必要がある。本研究の成果により治療後の再発の要因となりうるMRDを正確にモニタリングできる様になった点の社会的意義は大きい。また転移のマーカーがCAF由来であったのは、転移成立の本質を学術的に捉える上でシングルセル解析が可能になった現在だからこその結果であり、学術的に有意義であった。
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