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Clinical significance of PD-L1 and PD-L2 copy number gains in non-small-cell lung cancer
http://hdl.handle.net/10271/3219
http://hdl.handle.net/10271/32191a5ae6cb-8a3e-42ce-94f6-5c465790d5ac
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (10.0 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2018-03-06 | |||||||
| タイトル | ||||||||
| タイトル | Clinical significance of PD-L1 and PD-L2 copy number gains in non-small-cell lung cancer | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 主題 | PD-L1 | |||||||
| キーワード | ||||||||
| 主題 | PD-L2 | |||||||
| キーワード | ||||||||
| 主題 | amplification | |||||||
| キーワード | ||||||||
| 主題 | copy number | |||||||
| キーワード | ||||||||
| 主題 | non-small-cell lung cancer | |||||||
| 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 | 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 | |||||||
| 著者 |
Inoue, Yusuke
× Inoue, Yusuke
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| 書誌情報 |
en : Oncotarget 巻 7, 号 22, p. 32113-32128, 発行日 2016-04-01 |
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| 出版者 | ||||||||
| 出版者 | Impact Journals | |||||||
| 言語 | en | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | 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. | |||||||
| 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 | 2017-03-13 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲第744号 | |||||||
| EISSN | ||||||||
| 収録物識別子タイプ | EISSN | |||||||
| 収録物識別子 | 1949-2553 | |||||||
| PubMed番号 | ||||||||
| 識別子タイプ | PMID | |||||||
| 関連識別子 | 27050074 | |||||||
| 出版社DOI | ||||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | https://doi.org/10.18632/oncotarget.8528 | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | VoR | |||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
