Phosphoproteomics Enables Molecular Subtyping and Nomination of Kinase Candidates for Individual Patients of Diffuse-Type Gastric Cancer.

Abstract

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.

• Authors: 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
• Journal: iScience (iScience) Vol. 22 Pg. 44-57 (Dec 20 2019) ISSN: 2589-0042 [Electronic] United States
• PMID: 31751824 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.