iScience (Dec 2019)
Phosphoproteomics Enables Molecular Subtyping and Nomination of Kinase Candidates for Individual Patients of Diffuse-Type Gastric Cancer
- Mengsha Tong,
- Chunyu Yu,
- Jinwen Shi,
- Wenwen Huang,
- Sai Ge,
- Mingwei Liu,
- Lei Song,
- Dongdong Zhan,
- Xia Xia,
- Wanlin Liu,
- Jinwen Feng,
- Wenhao Shi,
- Jiafu Ji,
- Jing Gao,
- Tieliu Shi,
- Weimin Zhu,
- Chen Ding,
- Yi Wang,
- Fuchu He,
- Lin Shen,
- Tingting Li,
- Jun Qin
Affiliations
- Mengsha Tong
- State Key Laboratory of Proteomics, Joint Laboratory of Gastrointestinal Oncology, Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing Institute of Lifeomics, Beijing 102206, China; State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China
- Chunyu Yu
- Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
- Jinwen Shi
- State Key Laboratory of Proteomics, Joint Laboratory of Gastrointestinal Oncology, Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
- Wenwen Huang
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China
- Sai Ge
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China
- Mingwei Liu
- State Key Laboratory of Proteomics, Joint Laboratory of Gastrointestinal Oncology, Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
- Lei Song
- State Key Laboratory of Proteomics, Joint Laboratory of Gastrointestinal Oncology, Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
- Dongdong Zhan
- Center for Bioinformatics, East China Normal University, Shanghai 200241, China
- Xia Xia
- State Key Laboratory of Proteomics, Joint Laboratory of Gastrointestinal Oncology, Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
- Wanlin Liu
- State Key Laboratory of Proteomics, Joint Laboratory of Gastrointestinal Oncology, Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
- Jinwen Feng
- Center for Bioinformatics, East China Normal University, Shanghai 200241, China
- Wenhao Shi
- State Key Laboratory of Proteomics, Joint Laboratory of Gastrointestinal Oncology, Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
- Jiafu Ji
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China
- Jing Gao
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China
- Tieliu Shi
- Center for Bioinformatics, East China Normal University, Shanghai 200241, China
- Weimin Zhu
- State Key Laboratory of Proteomics, Joint Laboratory of Gastrointestinal Oncology, Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
- Chen Ding
- State Key Laboratory of Proteomics, Joint Laboratory of Gastrointestinal Oncology, Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing Institute of Lifeomics, Beijing 102206, China; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Fudan University, Shanghai 200433, China
- Yi Wang
- State Key Laboratory of Proteomics, Joint Laboratory of Gastrointestinal Oncology, Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
- Fuchu He
- State Key Laboratory of Proteomics, Joint Laboratory of Gastrointestinal Oncology, Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing Institute of Lifeomics, Beijing 102206, China; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Fudan University, Shanghai 200433, China; Corresponding author
- Lin Shen
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China; Corresponding author
- Tingting Li
- Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Corresponding author
- Jun Qin
- State Key Laboratory of Proteomics, Joint Laboratory of Gastrointestinal Oncology, Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing Institute of Lifeomics, Beijing 102206, China; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Fudan University, Shanghai 200433, China; Corresponding author
- Journal volume & issue
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Vol. 22
pp. 44 – 57
Abstract
Summary: The diffuse-type gastric cancer (DGC) constitutes a subgroup of gastric cancer with poor prognosis and no effective molecular therapies. Here, we report a phosphoproteomic landscape of DGC derived from 83 tumors together with their nearby tissues. Based on phosphorylation, DGC could be classified into three molecular subtypes with distinct overall survival (OS) and chemosensitivity. We identified 16 kinases whose activities were associated with poor OS. These activated kinases covered several cancer hallmark pathways, with the MTOR signaling network being the most frequently activated. We proposed a patient-specific strategy based on the hierarchy of clinically actionable kinases for prioritization of kinases for further clinical evaluation. Our global data analysis indicates that in addition to finding activated kinase pathways in DGC, large-scale phosphoproteomics could be used to classify DGCs into subtypes that are associated with distinct clinical outcomes as well as nomination of kinase targets that may be inhibited for cancer treatments. : Biological Sciences; Cancer Systems Biology; Proteomics; Systems Biology Subject Areas: Biological Sciences, Cancer Systems Biology, Proteomics, Systems Biology
