Comprehensive proteogenomic characterization of early duodenal cancer reveals the carcinogenesis tracks of different subtypes

Lingling Li, Dongxian Jiang, Hui Liu, Chunmei Guo, Rui Zhao, Qiao Zhang, Chen Xu, Zhaoyu Qin, Jinwen Feng, Yang Liu, Haixing Wang, Weijie Chen, Xue Zhang, Bin Li, Lin Bai, Sha Tian, Subei Tan, Zixiang Yu, Lingli Chen, Jie Huang, Jian-Yuan Zhao (), Yingyong Hou () and Chen Ding ()
Additional contact information
Lingling Li: Fudan University
Dongxian Jiang: Fudan University
Hui Liu: Henan Normal University
Chunmei Guo: Fudan University
Rui Zhao: Xinhua HospitalShanghai Jiao Tong University School of Medicine
Qiao Zhang: Fudan University
Chen Xu: Fudan University
Zhaoyu Qin: Fudan University
Jinwen Feng: Fudan University
Yang Liu: Fudan University
Haixing Wang: Fudan University
Weijie Chen: Fudan University
Xue Zhang: Fudan University
Bin Li: Fudan University
Lin Bai: Fudan University
Sha Tian: Fudan University
Subei Tan: Fudan University
Zixiang Yu: Fudan University
Lingli Chen: Fudan University
Jie Huang: Fudan University
Jian-Yuan Zhao: Xinhua HospitalShanghai Jiao Tong University School of Medicine
Yingyong Hou: Fudan University
Chen Ding: Fudan University

Nature Communications, 2023, vol. 14, issue 1, 1-24

Abstract: Abstract The subtypes of duodenal cancer (DC) are complicated and the carcinogenesis process is not well characterized. We present comprehensive characterization of 438 samples from 156 DC patients, covering 2 major and 5 rare subtypes. Proteogenomics reveals LYN amplification at the chromosome 8q gain functioned in the transmit from intraepithelial neoplasia phase to infiltration tumor phase via MAPK signaling, and illustrates the DST mutation improves mTOR signaling in the duodenal adenocarcinoma stage. Proteome-based analysis elucidates stage-specific molecular characterizations and carcinogenesis tracks, and defines the cancer-driving waves of the adenocarcinoma and Brunner’s gland subtypes. The drug-targetable alanyl-tRNA synthetase (AARS1) in the high tumor mutation burden/immune infiltration is significantly enhanced in DC progression, and catalyzes the lysine-alanylation of poly-ADP-ribose polymerases (PARP1), which decreases the apoptosis of cancer cells, eventually promoting cell proliferation and tumorigenesis. We assess the proteogenomic landscape of early DC, and provide insights into the molecular features corresponding therapeutic targets.

Date: 2023
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DOI: 10.1038/s41467-023-37221-5

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