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 () and Chen Ding ()
Additional contact information
Lingling Li: Fudan University
Dongxian Jiang: Zhongshan Hospital Fudan University
Qiao Zhang: Fudan University
Hui Liu: Fudan University
Fujiang Xu: The Affiliated Hospital of Southwest Medical University
Chunmei Guo: Fudan University
Zhaoyu Qin: Fudan University
Haixing Wang: Zhongshan Hospital Fudan University
Jinwen Feng: Fudan University
Yang Liu: Fudan University
Weijie Chen: Zhongshan Hospital Fudan University
Xue Zhang: Zhongshan Hospital Fudan University
Lin Bai: Fudan University
Sha Tian: Fudan University
Subei Tan: Fudan University
Chen Xu: Zhongshan Hospital Fudan University
Qi Song: Zhongshan Hospital Fudan University
Yalan Liu: Zhongshan Hospital Fudan University
Yunshi Zhong: Zhongshan Hospital Fudan University
Tianyin Chen: Zhongshan Hospital Fudan University
Pinghong Zhou: Zhongshan Hospital Fudan University
Jian-Yuan Zhao: Fudan University
Yingyong Hou: Zhongshan Hospital Fudan University
Chen Ding: Fudan University

Nature Communications, 2023, vol. 14, issue 1, 1-28

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-37440-w

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