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

Yan Li, Chen Xu, Bing Wang, Fujiang Xu, Fahan Ma, Yuanyuan Qu, Dongxian Jiang, Kai Li, Jinwen Feng, Sha Tian, Xiaohui Wu, Yunzhi Wang, Yang Liu, Zhaoyu Qin, Yalan Liu, Jing Qin, Qi Song, Xiaolei Zhang, Akesu Sujie, Jie Huang, Tianshu Liu (), Kuntang Shen (), Jian-Yuan Zhao (), Yingyong Hou () and Chen Ding ()
Additional contact information
Yan Li: Fudan University
Chen Xu: Fudan University
Bing Wang: Henan Normal University
Fujiang Xu: Fudan University
Fahan Ma: Fudan University
Yuanyuan Qu: Fudan University Shanghai Cancer Center
Dongxian Jiang: Fudan University
Kai Li: Fudan University
Jinwen Feng: Fudan University
Sha Tian: Fudan University
Xiaohui Wu: Fudan University
Yunzhi Wang: Fudan University
Yang Liu: Fudan University
Zhaoyu Qin: Fudan University
Yalan Liu: Fudan University
Jing Qin: Fudan University
Qi Song: Fudan University
Xiaolei Zhang: Fudan University
Akesu Sujie: Fudan University
Jie Huang: Fudan University
Tianshu Liu: Fudan University
Kuntang Shen: Fudan University
Jian-Yuan Zhao: Shanghai Jiao Tong University School of Medicine
Yingyong Hou: Fudan University
Chen Ding: Fudan University

Nature Communications, 2022, vol. 13, issue 1, 1-26

Abstract: Abstract 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-33282-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33282-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-33282-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().