Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer
| Autor: | Jeremy L. Davis, Bradford J. Wood, Xin Wei Wang, Kris Ylaya, Bao Tran, Yongmei Zhao, David E. Kleiner, Michael C. Kelly, Monika Mehta, Zachary Rae, Sean P. Martin, Jonathan M. Hernandez, Lichun Ma, Tim F. Greten, Stephen M. Hewitt, Maria O. Hernandez |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine Cancer Research Biopsy Cholangiocarcinoma Transcriptome chemistry.chemical_compound Antineoplastic Agents Immunological 0302 clinical medicine Tumor Microenvironment RNA-Seq Aged 80 and over Liver Neoplasms respiratory system Middle Aged Prognosis Progression-Free Survival Gene Expression Regulation Neoplastic Vascular endothelial growth factor Liver Oncology 030220 oncology & carcinogenesis Hepatocellular carcinoma Female Single-Cell Analysis Liver cancer Reprogramming Adult Carcinoma Hepatocellular DNA Copy Number Variations Tumor cells Biology Article 03 medical and health sciences medicine Hepatectomy Humans Aged Tumor microenvironment Genetic Variation Cell Biology medicine.disease Cytolysis Bile Ducts Intrahepatic 030104 developmental biology Bile Duct Neoplasms chemistry Drug Resistance Neoplasm Cancer research human activities |
| Zdroj: | Cancer Cell |
| ISSN: | 1535-6108 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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