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

Author

Listed:
  • 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
    Zhengzhou University)

  • Yingyong Hou

    (Fudan University)

  • Chen Ding

    (Fudan University)

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.

Suggested Citation

  • 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 & Su, 2023. "Comprehensive proteogenomic characterization of early duodenal cancer reveals the carcinogenesis tracks of different subtypes," Nature Communications, Nature, vol. 14(1), pages 1-24, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37221-5
    DOI: 10.1038/s41467-023-37221-5
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