YTHDF1 and YTHDF2 are associated with better patient survival and an inflamed tumor-immune microenvironment in non-small-cell lung cancer

• Material Type: 博士論文
• Title: YTHDF1 and YTHDF2 are associated with better patient survival and an inflamed tumor-immune microenvironment in non-small-cell lung cancer
• Author/Editor: 土屋, 一夫
• Author Heading: 土屋, 一夫
• Publication, Distribution, etc.: Taylor & Francis Group
• Publication Date: 2021-08-10
• Publication Date (W3CDTF): 2021-08-10
• Alternative Title: 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
• Degree grantor/type: 浜松医科大学
• Date Granted: 2022-03-14
• Date Granted (W3CDTF): 2022-03-14
• Dissertation Number: 甲第896号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Lung cancer; ythdf1; ythdf2; pd-l1; tumor-immune microenvironment; m6A
• Target Audience: 一般
• Note (General): doctoral; 医学系研究科; 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.
• Persistent ID (NDL): info:ndljp/pid/12651546; https://dl.ndl.go.jp/pid/12651546
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2023-03-02T11:18:10+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10271/00004213; https://hama-med.repo.nii.ac.jp/records/4091
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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