Clinical significance of PD-L1 and PD-L2 copy number gains in non-small-cell lung cancer

• Material Type: 博士論文
• Title: Clinical significance of PD-L1 and PD-L2 copy number gains in non-small-cell lung cancer
• Volume: 7 22
• Author/Editor: Inoue, Yusuke
• Author Heading: Inoue, Yusuke
• Publication, Distribution, etc.: Impact Journals
• Publication Date: 2016-04-01
• Publication Date (W3CDTF): 2016-04-01
• Alternative Title: 非小細胞肺がんにおけるPD-L1、PD-L2遺伝子コピー数増加の臨床的意義
• Periodical title: Oncotarget
• Degree grantor/type: 浜松医科大学
• Date Granted: 2017-03-13
• Date Granted (W3CDTF): 2017-03-13
• Dissertation Number: 甲第744号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第744号
• Text Language Code: eng
• Subject Heading: PD-L1; PD-L2; amplification; copy number; non-small-cell lung cancer
• Target Audience: 一般
• Note (General): doctoral; 医学系研究科; New reliable biomarkers are needed to predict the response to immune checkpoint inhibitors against programmed death-1 (PD-1) and its ligand (PD-L1), because PD-L1 expression on tumor cells has limited power for selecting patients who may benefit from such therapy. Here we investigated the significance of PD-L1 and PD-L2 gene copy number gains using fluorescence in situ hybridization as well as PD-L1 and PD-L2 expression in 654 patients with resected non-small-cell lung cancer. The prevalence of PD-L1 amplification and polysomy was 3.1% and 13.2%, respectively. The PD-L1 gene copy number status was in agreement with both the PD-L2 and Janus kinase 2 gene copy number statuses. PD-L1 and PD-L2 expression was observed in 30.7% and 13.1%, respectively. Both PD-L1 copy number gains and expression were associated with smoking-related tumors. Tumor cells with PD-L1 genomic gains exhibited significantly higher levels of PD-L1 expression than those without, but PD-L2 copy number gains were not related to PD-L2 augmentation. PD-L1 gene amplification and polysomy were independently associated with PD-L1 expression, with high immune infiltrates and EGFR expression in a multivariate logistic regression model. Comparative analysis between primary tumors and synchronous regional lymph node metastases revealed that the PD-L1 gene copy number alterations were highly consistent and reproducible compared with the PD-L1 expression. Both PD-L1 amplification and level of protein expression were predictors of poor survival using Cox univariate analyses. Therefore, we conclude that an increase in PD-L1 gene copy number can be a feasible alternative biomarker for predicting response to anti-PD-1/PD-L1 therapy.
• DOI: info:doi/10.18632/oncotarget.8528; https://doi.org/info:doi/10.18632/oncotarget.8528
• Persistent ID (NDL): info:ndljp/pid/11063585; https://dl.ndl.go.jp/pid/11063585
• 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): 2018-04-03T03:53:09+09:00
• Date Created (W3CDTF): 2018-08-27
• 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/10271/3219; https://hama-med.repo.nii.ac.jp/records/3077
• 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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