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YTHDF1 and YTHDF2 are associated with better patient survival and an inflamed tumor-immune microenvironment in non-small-cell lung cancer
http://hdl.handle.net/10271/00004213
http://hdl.handle.net/10271/00004213cce950b2-4f80-45ec-a9f8-edd37d0bf3a2
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (4.6 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2022-11-29 | |||||||
| タイトル | ||||||||
| タイトル | YTHDF1 and YTHDF2 are associated with better patient survival and an inflamed tumor-immune microenvironment in non-small-cell lung cancer | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 主題 | Lung cancer | |||||||
| キーワード | ||||||||
| 主題 | ythdf1 | |||||||
| キーワード | ||||||||
| 主題 | ythdf2 | |||||||
| キーワード | ||||||||
| 主題 | pd-l1 | |||||||
| キーワード | ||||||||
| 主題 | tumor-immune microenvironment | |||||||
| キーワード | ||||||||
| 主題 | m6A | |||||||
| 資源タイプ | ||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||
| 資源タイプ | doctoral thesis | |||||||
| アクセス権 | ||||||||
| アクセス権 | open access | |||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
| その他のタイトル | ||||||||
| その他のタイトル | YTHDF1およびYTHDF2は、非小細胞肺がん患者における生存率の向上および腫瘍-免疫微小環境の炎症と関連している | |||||||
| 著者 |
土屋, 一夫
× 土屋, 一夫
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| 書誌情報 |
en : OncoImmunology 巻 10, 号 1, p. 1962656, 発行日 2021-08-10 |
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| 出版者 | ||||||||
| 出版者 | Taylor & Francis Group | |||||||
| 言語 | en | |||||||
| 権利 | ||||||||
| 言語 | en | |||||||
| 権利情報 | Copyright 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. | |||||||
| 権利 | ||||||||
| 言語 | en | |||||||
| 権利情報 | This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | The human YTH domain family (YTHDF) proteins are RNA-binding proteins that recognize N6-methyladenosine (m6A), facilitating various biological processes via m6A RNA modification. How these molecules associate with non-small-cell lung cancer (NSCLC) molecular mechanisms remain unclear. The protein expression levels of YTHDF1 and YTHDF2 in 603 cases of resected NSCLC were evaluated using immunohistochemistry. We analyzed the associations of these attributes with patient characteristics and survival. We also assessed four subsets of lymphocytes (PD-1+, CD8+, Foxp3+, and CD45RO+) as tumorinfiltrating lymphocytes (TILs) in the tumor nest and in the surrounding stroma separately. In addition, we investigated differentially expressed genes and the expression of PD-L1 in YTHDF1- and YTHDF2- deprived lung cancer cells. The expressions of both YTHDF1 and YTHDF2 were less in the advancedstage tumors than in the early-stage tumors. The expressions of both YTHDF1 and YTHDF2 were also independent favorable prognostic factors for recurrence-free survival (HR, 0.745; 95% CI, 0.562-0.984 for YTHDF1; HR, 0.683; 95% CI, 0.503-0.928 for YTHDF2). The TIL densities of almost all four lymphocyte subsets in the stroma were significantly higher in the tumors with high YTHDF1 and YTHDF2 expression. In vitro, YTHDF1 and YTHDF2 knockdown in cells upregulated tumor PD-L1 expression and altered multiple immune-related genes. High expressions of both YTHDF1 and YTHDF2 are associated with a favorable prognostic outcome of NSCLC patients, a greater amount of TILs, and downregulation of PD-L1. YTHDF1 and YTHDF2 could be novel prognostic and druggable targets related to the tumor-immune microenvironment in lung cancers. | |||||||
| 言語 | en | |||||||
| 学位名 | ||||||||
| 学位名 | 博士（医学） | |||||||
| 学位の区分 | ||||||||
| 内容記述 | doctoral | |||||||
| 学位の分野 | ||||||||
| 内容記述 | 医学系研究科 | |||||||
| 学位授与機関 | ||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||
| 学位授与機関識別子 | 13802 | |||||||
| 学位授与機関名 | 浜松医科大学 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2022-03-14 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲第896号 | |||||||
| EISSN | ||||||||
| 収録物識別子タイプ | EISSN | |||||||
| 収録物識別子 | 2162-402X | |||||||
| PubMed番号 | ||||||||
| 識別子タイプ | PMID | |||||||
| 関連識別子 | 34408926 | |||||||
| 出版社DOI | ||||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | https://doi.org/10.1080/2162402X.2021.1962656 | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | VoR | |||||||
