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Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer

  1. Author:
    Ma, Lichun
    Hernandez,Maria
    Zhao,Yongmei
    Mehta,Monika
    Tran,Bao
    Kelly,Michael
    Rae,Zachary
    Hernandez, Jonathan M
    Davis, Jeremy L
    Martin, Sean P
    Kleiner, David E
    Hewitt, Stephen M
    Ylaya, Kris
    Wood, Bradford J
    Greten, Tim F
    Wang, Xin Wei

  2. Author Address

    Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA., Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 20701, USA., Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA., Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA., Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA., Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA., Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; NIH Center for Interventional Oncology, Bethesda, MD 20892, USA., Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA., Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: xw3u@nih.gov.,
    1. Year: 2019
    2. Date: Oct 14
    3. Epub Date: 2019 09 11
  2. Journal: Cancer cell
    1. 36
    2. 4
    3. Pages: 418-430
  4. Type of Article: Article
  5. Article Number: e6
  6. ISSN: 1535-6108
  1. Abstract:

    Cellular diversity in tumors is a key factor for therapeutic failures and lethal outcomes of solid malignancies. Here, we determined the single-cell transcriptomic landscape of liver cancer biospecimens from 19 patients. We found varying degrees of heterogeneity in malignant cells within and between tumors and diverse landscapes of tumor microenvironment (TME). Strikingly, tumors with higher transcriptomic diversity were associated with patient's worse overall survival. We found a link between hypoxia-dependent vascular endothelial growth factor expression in tumor diversity and TME polarization. Moreover, T cells from higher heterogeneous tumors showed lower cytolytic activities. Consistent results were found using bulk genomic and transcriptomic profiles of 765 liver tumors. Our results offer insight into the diverse ecosystem of liver cancer and its impact on patient prognosis. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.ccell.2019.08.007
  3. PMID: 31588021
  4. View record in Web of Science®
  5. WOS: 000489949400009
  6. PII : S1535-6108(19)30375-7

Library Notes

  1. Fiscal Year: FY2019-2020
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