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Proteomic characterization of gastric cancer response to chemotherapy and targeted therapy reveals new 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.
Affiliation
  • Li Y; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, 200433, China.
  • Xu C; Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Wang B; State Key Laboratory of Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan center for outstanding overseas scientists of pulmonary fibrosis, College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, 453007, China.
  • Xu F; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, 200433, China.
  • Ma F; Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
  • Qu Y; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, 200433, China.
  • Jiang D; Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
  • Li K; Department of Oncology, Shanghai Medical College, Shanghai, 200032, China.
  • Feng J; Shanghai Genitourinary Cancer Institute, Shanghai, 200032, China.
  • Tian S; Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Wu X; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, 200433, China.
  • Wang Y; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, 200433, China.
  • Liu Y; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, 200433, China.
  • Qin Z; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, 200433, China.
  • Liu Y; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, 200433, China.
  • Qin J; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, 200433, China.
  • Song Q; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, 200433, China.
  • Zhang X; Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Sujie A; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Huang J; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, 200433, China.
  • Liu T; Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Shen K; Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Zhao JY; Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • Hou Y; Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. liu.tianshu@zs-hospital.sh.cn.
  • Ding C; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. shen.kuntang@zs-hospital.sh.cn.
Nat Commun ; 13(1): 5723, 2022 09 29.
Article in En | MEDLINE | ID: mdl-36175412
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stomach Neoplasms / Proteomics Type of study: Prognostic_studies Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2022 Document type: Article Affiliation country: China
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stomach Neoplasms / Proteomics Type of study: Prognostic_studies Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2022 Document type: Article Affiliation country: China