Tong Mengsha, Yu Chunyu, Shi Jinwen, Huang Wenwen, Ge Sai, Liu Mingwei, Song Lei, Zhan Dongdong, Xia Xia, Liu Wanlin, Feng Jinwen, Shi Wenhao, Ji Jiafu, Gao Jing, Shi Tieliu, Zhu Weimin, Ding Chen, Wang Yi, He Fuchu, Shen Lin, Li Tingting, Qin Jun
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.
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.
iScience. 2019 Dec 20;22:44-57. doi: 10.1016/j.isci.2019.11.003. Epub 2019 Nov 6.
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.
弥漫型胃癌（DGC）是胃癌的一个亚组，预后较差且尚无有效的分子疗法。在此，我们报告了源自83个肿瘤及其邻近组织的DGC磷酸化蛋白质组图谱。基于磷酸化情况，DGC可分为三种分子亚型，其总生存期（OS）和化疗敏感性各不相同。我们鉴定出16种激酶，其活性与较差的OS相关。这些激活的激酶涵盖了多个癌症标志性通路，其中MTOR信号网络激活最为频繁。我们基于临床可操作激酶的层次结构提出了一种针对患者的策略，以便对激酶进行优先级排序，用于进一步的临床评估。我们的全局数据分析表明，除了在DGC中发现激活的激酶通路外，大规模磷酸化蛋白质组学还可用于将DGC分类为与不同临床结果相关的亚型，以及提名可能用于癌症治疗的可被抑制的激酶靶点。
