| Literature DB >> 36175412 |
Yan Li1, Chen Xu2, Bing Wang3, Fujiang Xu1,4, Fahan Ma1, Yuanyuan Qu5,6,7, Dongxian Jiang2, Kai Li1, Jinwen Feng1, Sha Tian1, Xiaohui Wu1, Yunzhi Wang1, Yang Liu1, Zhaoyu Qin1, Yalan Liu2, Jing Qin8, Qi Song1, Xiaolei Zhang2, Akesu Sujie2, Jie Huang2, Tianshu Liu9, Kuntang Shen10, Jian-Yuan Zhao11,12, Yingyong Hou13, Chen Ding14.
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.Entities:
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Year: 2022 PMID： 36175412 PMCID： PMC9522856 DOI： 10.1038/s41467-022-33282-0
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 17.694