Proteomic characterization of gastric cancer response to chemotherapy and targeted therapy reveals new therapeutic strategies

Nat Commun. 2022 Sep 29;13(1):5723. doi: 10.1038/s41467-022-33282-0.

Yan Li ^# ¹, Chen Xu ^# ², Bing Wang ^# ³, Fujiang Xu ^# ¹ ⁴, Fahan Ma ^# ¹, Yuanyuan Qu ⁵ ⁶ ⁷, Dongxian Jiang ², Kai Li ¹, Jinwen Feng ¹, Sha Tian ¹, Xiaohui Wu ¹, Yunzhi Wang ¹, Yang Liu ¹, Zhaoyu Qin ¹, Yalan Liu ², Jing Qin ⁸, Qi Song ¹, Xiaolei Zhang ², Akesu Sujie ², Jie Huang ², Tianshu Liu ⁹, Kuntang Shen ¹⁰, Jian-Yuan Zhao ¹¹ ¹², Yingyong Hou ¹³, Chen Ding ¹⁴

Affiliations

1 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.
2 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
3 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.
4 Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
5 Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
6 Department of Oncology, Shanghai Medical College, Shanghai, 200032, China.
7 Shanghai Genitourinary Cancer Institute, Shanghai, 200032, China.
8 Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
9 Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. [email protected].
10 Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. [email protected].
11 Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. [email protected].
12 Department of Anatomy and Neuroscience Research Institute, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China. [email protected].
13 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. [email protected].
14 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. [email protected].
# Contributed equally.

PMID: 36175412 DOI: 10.1038/s41467-022-33282-0

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.

Products

Cat. No.

Product Name

Description

Target

Research Area
HY-70063

Buparlisib

99.90%, PI3K Inhibitor

PI3K; Apoptosis

Cancer

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