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Proteomic characterization of gastric cancer response to chemotherapy and targeted therapy reveals potential therapeutic strategies

Chemotherapy and targeted therapy are the major treatments for gastric cancer (GC), but drug resistance limits its effectiveness. Here, we profile the proteome of 206 tumor tissues from patients with GC undergoing either chemotherapy or anti-HER2-based therapy. Proteome-based classification reveals...

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Autores principales: Li, Yan, Xu, Chen, Wang, Bing, Xu, Fujiang, Ma, Fahan, Qu, Yuanyuan, Jiang, Dongxian, Li, Kai, Feng, Jinwen, Tian, Sha, Wu, Xiaohui, Wang, Yunzhi, Liu, Yang, Qin, Zhaoyu, Liu, Yalan, Qin, Jing, Song, Qi, Zhang, Xiaolei, Sujie, Akesu, Huang, Jie, Liu, Tianshu, Shen, Kuntang, Zhao, Jian-Yuan, Hou, Yingyong, Ding, Chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9522856/
https://www.ncbi.nlm.nih.gov/pubmed/36175412
http://dx.doi.org/10.1038/s41467-022-33282-0
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author Li, Yan
Xu, Chen
Wang, Bing
Xu, Fujiang
Ma, Fahan
Qu, Yuanyuan
Jiang, Dongxian
Li, Kai
Feng, Jinwen
Tian, Sha
Wu, Xiaohui
Wang, Yunzhi
Liu, Yang
Qin, Zhaoyu
Liu, Yalan
Qin, Jing
Song, Qi
Zhang, Xiaolei
Sujie, Akesu
Huang, Jie
Liu, Tianshu
Shen, Kuntang
Zhao, Jian-Yuan
Hou, Yingyong
Ding, Chen
author_facet Li, Yan
Xu, Chen
Wang, Bing
Xu, Fujiang
Ma, Fahan
Qu, Yuanyuan
Jiang, Dongxian
Li, Kai
Feng, Jinwen
Tian, Sha
Wu, Xiaohui
Wang, Yunzhi
Liu, Yang
Qin, Zhaoyu
Liu, Yalan
Qin, Jing
Song, Qi
Zhang, Xiaolei
Sujie, Akesu
Huang, Jie
Liu, Tianshu
Shen, Kuntang
Zhao, Jian-Yuan
Hou, Yingyong
Ding, Chen
author_sort Li, Yan
collection PubMed
description Chemotherapy and targeted therapy are the major treatments for gastric cancer (GC), but drug resistance limits its effectiveness. Here, we profile the proteome of 206 tumor tissues from patients with GC undergoing either chemotherapy or anti-HER2-based therapy. Proteome-based classification reveals four subtypes (G-I–G-IV) related to different clinical and molecular features. MSI-sig high GC patients benefit from docetaxel combination treatment, accompanied by anticancer immune response. Further study reveals patients with high T cell receptor signaling respond to anti-HER2-based therapy; while activation of extracellular matrix/PI3K-AKT pathway impair anti-tumor effect of trastuzumab. We observe CTSE functions as a cell intrinsic enhancer of chemosensitivity of docetaxel, whereas TKTL1 functions as an attenuator. Finally, we develop prognostic models with high accuracy to predict therapeutic response, further validated in an independent validation cohort. This study provides a rich resource for investigating the mechanisms and indicators of chemotherapy and targeted therapy in GC.
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spelling pubmed-95228562022-10-01 Proteomic characterization of gastric cancer response to chemotherapy and targeted therapy reveals potential therapeutic strategies Li, Yan Xu, Chen Wang, Bing Xu, Fujiang Ma, Fahan Qu, Yuanyuan Jiang, Dongxian Li, Kai Feng, Jinwen Tian, Sha Wu, Xiaohui Wang, Yunzhi Liu, Yang Qin, Zhaoyu Liu, Yalan Qin, Jing Song, Qi Zhang, Xiaolei Sujie, Akesu Huang, Jie Liu, Tianshu Shen, Kuntang Zhao, Jian-Yuan Hou, Yingyong Ding, Chen Nat Commun Article Chemotherapy and targeted therapy are the major treatments for gastric cancer (GC), but drug resistance limits its effectiveness. Here, we profile the proteome of 206 tumor tissues from patients with GC undergoing either chemotherapy or anti-HER2-based therapy. Proteome-based classification reveals four subtypes (G-I–G-IV) related to different clinical and molecular features. MSI-sig high GC patients benefit from docetaxel combination treatment, accompanied by anticancer immune response. Further study reveals patients with high T cell receptor signaling respond to anti-HER2-based therapy; while activation of extracellular matrix/PI3K-AKT pathway impair anti-tumor effect of trastuzumab. We observe CTSE functions as a cell intrinsic enhancer of chemosensitivity of docetaxel, whereas TKTL1 functions as an attenuator. Finally, we develop prognostic models with high accuracy to predict therapeutic response, further validated in an independent validation cohort. This study provides a rich resource for investigating the mechanisms and indicators of chemotherapy and targeted therapy in GC. Nature Publishing Group UK 2022-09-29 /pmc/articles/PMC9522856/ /pubmed/36175412 http://dx.doi.org/10.1038/s41467-022-33282-0 Text en © The Author(s) 2022, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Li, Yan
Xu, Chen
Wang, Bing
Xu, Fujiang
Ma, Fahan
Qu, Yuanyuan
Jiang, Dongxian
Li, Kai
Feng, Jinwen
Tian, Sha
Wu, Xiaohui
Wang, Yunzhi
Liu, Yang
Qin, Zhaoyu
Liu, Yalan
Qin, Jing
Song, Qi
Zhang, Xiaolei
Sujie, Akesu
Huang, Jie
Liu, Tianshu
Shen, Kuntang
Zhao, Jian-Yuan
Hou, Yingyong
Ding, Chen
Proteomic characterization of gastric cancer response to chemotherapy and targeted therapy reveals potential therapeutic strategies
title Proteomic characterization of gastric cancer response to chemotherapy and targeted therapy reveals potential therapeutic strategies
title_full Proteomic characterization of gastric cancer response to chemotherapy and targeted therapy reveals potential therapeutic strategies
title_fullStr Proteomic characterization of gastric cancer response to chemotherapy and targeted therapy reveals potential therapeutic strategies
title_full_unstemmed Proteomic characterization of gastric cancer response to chemotherapy and targeted therapy reveals potential therapeutic strategies
title_short Proteomic characterization of gastric cancer response to chemotherapy and targeted therapy reveals potential therapeutic strategies
title_sort proteomic characterization of gastric cancer response to chemotherapy and targeted therapy reveals potential therapeutic strategies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9522856/
https://www.ncbi.nlm.nih.gov/pubmed/36175412
http://dx.doi.org/10.1038/s41467-022-33282-0
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