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Multilevel proteomic analyses reveal molecular diversity between diffuse-type and intestinal-type gastric cancer

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Listed:
  • Wenhao Shi

    (Tsinghua University
    Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX center, Beijing), Beijing Institute of Lifeomics)

  • Yushen Wang

    (Tsinghua University
    Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX center, Beijing), Beijing Institute of Lifeomics)

  • Chen Xu

    (Zhongshan Hospital, Fudan University)

  • Yan Li

    (School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University)

  • Sai Ge

    (Peking University Cancer Hospital and Institute)

  • Bin Bai

    (Xijing Hospital of Digestive Diseases, Fourth Military Medical University)

  • Kecheng Zhang

    (Chinese PLA General Hospital First Medical Center)

  • Yunzhi Wang

    (School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University)

  • Nairen Zheng

    (Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX center, Beijing), Beijing Institute of Lifeomics)

  • Juan Wang

    (Xijing Hospital of Digestive Diseases, Fourth Military Medical University)

  • Shiqi Wang

    (Xijing Hospital of Digestive Diseases, Fourth Military Medical University)

  • Gang Ji

    (Xijing Hospital of Digestive Diseases, Fourth Military Medical University)

  • Jipeng Li

    (Xijing Hospital of Digestive Diseases, Fourth Military Medical University)

  • Yongzhan Nie

    (Xijing Hospital of Digestive Diseases, Fourth Military Medical University)

  • Wenquan Liang

    (Chinese PLA General Hospital First Medical Center)

  • Xiaosong Wu

    (Chinese PLA General Hospital First Medical Center)

  • Jianxin Cui

    (Chinese PLA General Hospital First Medical Center)

  • Yi Wang

    (Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX center, Beijing), Beijing Institute of Lifeomics)

  • Lin Chen

    (Chinese PLA General Hospital First Medical Center)

  • Qingchuan Zhao

    (Xijing Hospital of Digestive Diseases, Fourth Military Medical University)

  • Lin Shen

    (Peking University Cancer Hospital and Institute)

  • Fuchu He

    (Tsinghua University
    Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX center, Beijing), Beijing Institute of Lifeomics
    Chinese Academy of Medical Sciences)

  • Jun Qin

    (Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX center, Beijing), Beijing Institute of Lifeomics
    School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University)

  • Chen Ding

    (Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX center, Beijing), Beijing Institute of Lifeomics
    School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University)

Abstract

Diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer (IGC) are the major histological types of gastric cancer (GC). The molecular mechanism underlying DGC and IGC differences are poorly understood. In this research, we carry out multilevel proteomic analyses, including proteome, phospho-proteome, and transcription factor (TF) activity profiles, of 196 cases covering DGC and IGC in Chinese patients. Integrative proteogenomic analysis reveals ARIDIA mutation associated with opposite prognostic effects between DGC and IGC, via diverse influences on their corresponding proteomes. Systematical comparison and consensus clustering analysis identify three subtypes of DGC and IGC, respectively, based on distinct patterns of the cell cycle, extracellular matrix organization, and immune response-related proteins expression. TF activity-based subtypes demonstrate that the disease progressions of DGC and IGC were regulated by SWI/SNF and NFKB complexes. Furthermore, inferred immune cell infiltration and immune clustering show Th1/Th2 ratio is an indicator for immunotherapeutic effectiveness, which is validated in an independent GC anti-PD1 therapeutic patient group. Our multilevel proteomic analyses enable a more comprehensive understanding of GC and can further advance the precision medicine.

Suggested Citation

  • Wenhao Shi & Yushen Wang & Chen Xu & Yan Li & Sai Ge & Bin Bai & Kecheng Zhang & Yunzhi Wang & Nairen Zheng & Juan Wang & Shiqi Wang & Gang Ji & Jipeng Li & Yongzhan Nie & Wenquan Liang & Xiaosong Wu , 2023. "Multilevel proteomic analyses reveal molecular diversity between diffuse-type and intestinal-type gastric cancer," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35797-6
    DOI: 10.1038/s41467-023-35797-6
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    References listed on IDEAS

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    1. Sai Ge & Xia Xia & Chen Ding & Bei Zhen & Quan Zhou & Jinwen Feng & Jiajia Yuan & Rui Chen & Yumei Li & Zhongqi Ge & Jiafu Ji & Lianhai Zhang & Jiayuan Wang & Zhongwu Li & Yumei Lai & Ying Hu & Yanyan, 2018. "A proteomic landscape of diffuse-type gastric cancer," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    2. Sai Ge & Xia Xia & Chen Ding & Bei Zhen & Quan Zhou & Jinwen Feng & Jiajia Yuan & Rui Chen & Yumei Li & Zhongqi Ge & Jiafu Ji & Lianhai Zhang & Jiayuan Wang & Zhongwu Li & Yumei Lai & Ying Hu & Yanyan, 2018. "Author Correction: A proteomic landscape of diffuse-type gastric cancer," Nature Communications, Nature, vol. 9(1), pages 1-1, December.
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    1. Yan Li & Bing Wang & Wentao Yang & Fahan Ma & Jianling Zou & Kai Li & Subei Tan & Jinwen Feng & Yunzhi Wang & Zhaoyu Qin & Zhiyu Chen & Chen Ding, 2024. "Longitudinal plasma proteome profiling reveals the diversity of biomarkers for diagnosis and cetuximab therapy response of colorectal cancer," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

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