| アイテムタイプ |
共通アイテムタイプ(1) |
| 公開日 |
2025-02-27 |
| タイトル |
|
|
タイトル |
Targeted Dynamic Phospho-Proteogenomic Analysis of Gastric Cancer Cells Suggests Host Immunity Provides Survival Benefit |
|
言語 |
en |
| その他のタイトル |
|
|
その他のタイトル |
Targeted dynamic phospho-proteogenomic analysis of gastric cancer cells suggests host immunity provides survival benefit |
|
言語 |
en |
| 著者 |
Kume, Kohei
飯田, 緑
Iwaya, Takeshi
Yashima-Abo, Akiko
Koizumi, Yuka
Endo, Akari
Wade, Kaitlin
Hiraki, Hayato
Calvert, Valerie
Wulfkuhle, Julia
Espina, Virginia
Siwak, Doris R.
Lu, Yiling
竹本, 和広
Suzuki, Yutaka
Sasaki, Yasushi
Tokino, Takashi
Petricoin, Emanuel III
Liotta, Lance A.
Mills, Gordon B.
Nishizuka, Satoshi S.
|
| 著作権関連情報 |
|
|
権利情報Resource |
http://creativecommons.org/licenses/by/4.0/ |
|
権利情報 |
Copyright (c) 2024 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
|
言語 |
en |
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Despite of massive emergence of molecular targeting drugs, the mainstay of advanced gastric cancer (GC) therapy is DNA-damaging drugs. Using a reverse-phase protein array-based proteogenomic analysis of a panel of 8 GC cell lines, we identified genetic alterations and signaling pathways, potentially associated with resistance to DNA-damaging drugs, including 5-fluorouracil (5FU), cisplatin, and etoposide. Resistance to cisplatin and etoposide, but not 5FU, was negatively associated with global copy number loss, vimentin expression, and caspase activity, which are considered hallmarks of previously established EMT subtype. The segregation of 19,392 protein expression time courses by sensitive and resistant cell lines for the drugs tested revealed that 5FU-resistant cell lines had lower changes in global protein dynamics, suggesting their robust protein level regulation, than their sensitive counterparts, whereas the cell lines that are resistant to other drugs showed increased protein dynamics in response to each drug. Despite faint global protein dynamics, 5FU-resistant cell lines showed increased signal transducer and activator of transcription 1 phosphorylation and PD-L1 expression in response to 5FU. In publicly available cohort data, expression of signal transducer and activator of transcription 1 and NFκB target genes induced by proinflammatory cytokines was associated with prolonged survival in GC. In our validation cohort, total lymphocyte count, rather than PD-L1 positivity, predicted a better relapse-free survival rate in GC patients with 5FU-based adjuvant chemotherapy than those with surgery alone. Moreover, total lymphocyte count+ patients who had no survival benefit from adjuvant chemotherapy were discriminated by expression of IκBα, a potent negative regulator of NFκB. Collectively, our results suggest that 5FU resistance observed in cell lines may be overcome by host immunity or by combination therapy with immune checkpoint blockade. |
|
言語 |
en |
| 書誌情報 |
en : Molecular & Cellular Proteomics
巻 23,
号 12,
p. 100870,
発行日 2024-11-21
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| 出版社 |
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|
出版者 |
Elsevier |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
5-fluorouracil |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
cisplatin |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
copy number variation |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
gastric cancer |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
NFκB |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
PD-L1 |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
proteogenomics |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
STAT1 |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
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|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| DOI |
|
|
関連タイプ |
isIdenticalTo |
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|
識別子タイプ |
DOI |
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|
関連識別子 |
https://doi.org/10.1016/j.mcpro.2024.100870 |
| ISSN |
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|
収録物識別子タイプ |
PISSN |
|
収録物識別子 |
1535-9476 |
| ISSN |
|
|
収録物識別子タイプ |
EISSN |
|
収録物識別子 |
1535-9484 |
| 研究者情報 |
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|
URL |
https://hyokadb02.jimu.kyutech.ac.jp/html/100000509_ja.html |
| 論文ID（連携） |
|
|
値 |
10448770 |
| 連携ID |
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|
値 |
13049 |
10448770.pdf (4.5 MB)
