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Integrative proteogenomic characterization of early esophageal cancer

Author

Listed:
  • 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
    Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
    School of Basic Medical Sciences, Zhengzhou University)

  • Yingyong Hou

    (Zhongshan Hospital Fudan University)

  • Chen Ding

    (Fudan University)

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.

Suggested Citation

  • 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, 2023. "Integrative proteogenomic characterization of early esophageal cancer," Nature Communications, Nature, vol. 14(1), pages 1-28, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37440-w
    DOI: 10.1038/s41467-023-37440-w
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