| Autor: |
Kunal S. Patel, Kaleab K. Tessema, Riki Kawaguchi, Alvaro G. Alvarado, Sree Deepthi Muthukrishnan, Akifumi Hagiwara, Vivek Swarup, Linda M. Liau, Anthony Wang, William Yong, Daniel H. Geschwind, Ichiro Nakano, Steven A. Goldman, Richard Everson, Benjamin M. Ellingson, Harley I. Kornblum |
| Rok vydání: |
2022 |
| Popis: |
Non-enhancing (NE) infiltrating tumor cells beyond the contrast-enhancing (CE) bulk of tumor are potential propagators of recurrence after gross total resection of high-grade glioma. We leveraged single-nucleus RNA-sequencing to compare prospectively identified biopsy specimens from CE and NE regions. Recurrent gliomas recapitulate the previously reported glioma cellular states of primary gliomas. Tumor cells in NE regions are enriched in oligodendrocyte progenitor cell-like and neural progenitor cell-like cellular states, while CE regions are enriched for astrocyte-like and mesenchymal-like states. These NE glioma cells have similar copy number alterations and proportions of proliferative and putative glioma stem cells relative to CE regions. Tumor cells in NE regions exhibit upregulation of genes previously associated with lower grade gliomas. Cell-, gene-, and pathway-level analyses of the tumor microenvironment in the NE region reveal relative downregulation of tumor-mediated neovascularization and cell-mediated immune response, but increased glioma-to-neuron interactions. This comprehensive analysis illustrates differing tumor and non-tumor landscapes of CE and NE regions in high-grade gliomas, highlighting the NE region as an area harboring likely initiators of recurrence in a pro-tumor microenvironment and identifying possible targets for future design of NE-specific adjuvant therapy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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