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Single-cell transcriptomic analysis suggests two molecularly distinct subtypes of intrahepatic cholangiocarcinoma

Author

Listed:
  • Guohe Song

    (Fudan University)

  • Yang Shi

    (Peking University)

  • Lu Meng

    (Institut Pasteur of Shanghai, Chinese Academy of Sciences)

  • Jiaqiang Ma

    (Fudan University
    Institut Pasteur of Shanghai, Chinese Academy of Sciences)

  • Siyuan Huang

    (Peking University)

  • Juan Zhang

    (Fudan University)

  • Yingcheng Wu

    (Fudan University)

  • Jiaxin Li

    (Peking University)

  • Youpei Lin

    (Fudan University)

  • Shuaixi Yang

    (Fudan University)

  • Dongning Rao

    (Fudan University)

  • Yifei Cheng

    (Fudan University)

  • Jian Lin

    (Fudan University)

  • Shuyi Ji

    (Fudan University)

  • Yuming Liu

    (Fudan University)

  • Shan Jiang

    (Institut Pasteur of Shanghai, Chinese Academy of Sciences)

  • Xiaoliang Wang

    (Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University)

  • Shu Zhang

    (Fudan University)

  • Aiwu Ke

    (Fudan University)

  • Xiaoying Wang

    (Fudan University)

  • Ya Cao

    (Central South University)

  • Yuan Ji

    (Fudan University)

  • Jian Zhou

    (Fudan University
    Fudan University)

  • Jia Fan

    (Fudan University
    Fudan University)

  • Xiaoming Zhang

    (Institut Pasteur of Shanghai, Chinese Academy of Sciences)

  • Ruibin Xi

    (Peking University)

  • Qiang Gao

    (Fudan University)

Abstract

Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous cancer with limited understanding of its classification and tumor microenvironment. Here, by performing single-cell RNA sequencing on 144,878 cells from 14 pairs of iCCA tumors and non-tumor liver tissues, we find that S100P and SPP1 are two markers for iCCA perihilar large duct type (iCCAphl) and peripheral small duct type (iCCApps). S100P + SPP1− iCCAphl has significantly reduced levels of infiltrating CD4+ T cells, CD56+ NK cells, and increased CCL18+ macrophages and PD1+CD8+ T cells compared to S100P-SPP1 + iCCApps. The transcription factor CREB3L1 is identified to regulate the S100P expression and promote tumor cell invasion. S100P-SPP1 + iCCApps has significantly more SPP1+ macrophage infiltration, less aggressiveness and better survival than S100P + SPP1− iCCAphl. Moreover, S100P-SPP1 + iCCApps harbors tumor cells at different status of differentiation, such as ALB + hepatocyte differentiation and ID3+ stemness. Our study extends the understanding of the diversity of tumor cells in iCCA.

Suggested Citation

  • Guohe Song & Yang Shi & Lu Meng & Jiaqiang Ma & Siyuan Huang & Juan Zhang & Yingcheng Wu & Jiaxin Li & Youpei Lin & Shuaixi Yang & Dongning Rao & Yifei Cheng & Jian Lin & Shuyi Ji & Yuming Liu & Shan , 2022. "Single-cell transcriptomic analysis suggests two molecularly distinct subtypes of intrahepatic cholangiocarcinoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29164-0
    DOI: 10.1038/s41467-022-29164-0
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    References listed on IDEAS

    as
    1. Zhengtao Xiao & Ziwei Dai & Jason W. Locasale, 2019. "Metabolic landscape of the tumor microenvironment at single cell resolution," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
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