2022 Fiscal Year Final Research Report
Genomic and epigenomic analysis of lung pleomorphic carcinoma for the development of new treatments
| Project/Area Number |
20K15771
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 43050:Genome biology-related
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 肺多形癌 / 肉腫様癌 / エピゲノム / DNAメチル化異常 / 腫瘍内不均一性 |
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| Outline of Final Research Achievements |
Surgical specimens of lung pleomorphic carcinoma were microscopically divided into normal lung tissue, epithelial-like component, and sarcoma-like component, and subjected to comprehensive DNA methylation analysis. Comparative analysis of DNA methylation rates in each region suggested that changes in gene expression due to DNA methylation are involved in carcinogenesis and morphological differentiation of lung pleomorphic carcinoma. We identified several intracellular signaling pathways significantly affected by DNA methylation sites involved in carcinogenesis, including the FGF signaling pathway, the TGF-beta family, and WNT/Beta-catenin signaling. In addition, we identified five genes (THSD1, ZFYVE21, CDT1, LYPD1, BGLAP) correlated with lymph node metastasis and lymphatic invasion, and three genes (LOC101927151, NRN1L, PLCXD3) correlated with recurrence and survival from the DNA methylation regions involved in carcinogenesis and differentiation to sarcoma-like components.
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| Free Research Field |
医学（ゲノム生物学関連）, 肺がんゲノム・エピゲノム異常
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| Academic Significance and Societal Importance of the Research Achievements |
学術的には肉腫様組織への形態変化という悪性進展を示唆する病理学的腫瘍内不均一性にDNAメチル化の関与を科学的に示したことにより, 高悪性度腫瘍に対するエピゲノム異常を標的とした新規治療開発への基礎的知見を示したと言える.
社会的意義としても昨今保険診療にがんゲノムプロファイリングが使用可能となり, 今後の個別化がん医療の推進が進めばゲノム異常だけでなくこのようなエピゲノム異常も治療に直結する臨床情報になり得る可能性を提起したと言えるだろう.
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