Integrative proteogenomic characterization of early esophageal cancer

Lingling Li; Dongxian Jiang; Qiao Zhang; Hui Liu; Fujiang Xu; Chunmei Guo; Zhaoyu Qin; Haixing Wang; Jinwen Feng; Yang Liu; Weijie Chen; Xue Zhang; Lin Bai; Sha Tian; Subei Tan; Chen Xu; Qi Song; Yalan Liu; Yunshi Zhong; Tianyin Chen; Pinghong Zhou; Jian-Yuan Zhao; Yingyong Hou; Chen Ding

doi:10.1038/s41467-023-37440-w

Integrative proteogenomic characterization of early esophageal cancer

Nat Commun. 2023 Mar 25;14(1):1666. doi: 10.1038/s41467-023-37440-w.

Authors

Lingling Li^#¹, Dongxian Jiang^#², Qiao Zhang^#¹, Hui Liu^#¹, Fujiang Xu^#³, Chunmei Guo^#¹, Zhaoyu Qin^#¹, Haixing Wang^#², Jinwen Feng¹, Yang Liu¹, Weijie Chen², Xue Zhang², Lin Bai¹, Sha Tian¹, Subei Tan¹, Chen Xu², Qi Song², Yalan Liu², Yunshi Zhong², Tianyin Chen², Pinghong Zhou⁴, Jian-Yuan Zhao^{5

6

7}, Yingyong Hou⁸, Chen Ding⁹

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 Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
⁴ Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital Fudan University, Shanghai, 200032, China. zhou.pinghong@zs-hospital.sh.cn.
⁵ 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. zhaojy@fudan.edu.cn.
⁶ Institute for Development 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. zhaojy@fudan.edu.cn.
⁷ Department of Anatomy and Neuroscience Research Institute , School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China. zhaojy@fudan.edu.cn.
⁸ Department of Pathology, Zhongshan Hospital Fudan University, Shanghai, 200032, China. hou.yingyong@zs-hospital.sh.cn.
⁹ 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. chend@fudan.edu.cn.

^# Contributed equally.

Abstract

Esophageal squamous cell carcinoma (ESCC) is malignant while the carcinogenesis is still unclear. Here, we perform a comprehensive multi-omics analysis of 786 trace-tumor-samples from 154 ESCC patients, covering 9 histopathological stages and 3 phases. Proteogenomics elucidates cancer-driving waves in ESCC progression, and reveals the molecular characterization of alcohol drinking habit associated signatures. We discover chromosome 3q gain functions in the transmit from nontumor to intraepithelial neoplasia phases, and find TP53 mutation enhances DNA replication in intraepithelial neoplasia phase. The mutations of AKAP9 and MCAF1 upregulate glycolysis and Wnt signaling, respectively, in advanced-stage ESCC phase. Six major tracks related to different clinical features during ESCC progression are identified, which is validated by an independent cohort with another 256 samples. Hyperphosphorylated phosphoglycerate kinase 1 (PGK1, S203) is considered as a drug target in ESCC progression. This study provides insight into the understanding of ESCC molecular mechanism and the development of therapeutic targets.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Squamous Cell* / genetics
Esophageal Neoplasms* / genetics
Esophageal Neoplasms* / pathology
Esophageal Squamous Cell Carcinoma* / genetics
Humans
Mutation
Proteogenomics*