Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer

By Lichun Ma, M. Hernandez, Yongmei Zhao, M. Mehta, Bao Tran, Michael Kelly, Zachary Rae, Jonathan M. Hernandez, Jeremy L. Davis, Sean P. Martin and 6 more. Cancer Cell, 2019

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SUMMARY Cellular diversity in tumors is 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 VEGF expression in tumor diversity and TME polarization. Moreover, T cells from higher heterogenous 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.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/774eb838f69214966a28ab4b7ea521974a38be8c