Single-nucleus expression characterization of non-enhancing region of recurrent high-grade glioma
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Single-nucleus expression characterization of non-enhancing region of recurrent high-grade glioma. / Patel, Kunal S.; Tessema, Kaleab K.; Kawaguchi, Riki; Dudley, Lindsey; Alvarado, Alvaro G.; Muthukrishnan, Sree Deepthi; Perryman, Travis; Hagiwara, Akifumi; Swarup, Vivek; Liau, Linda M.; Wang, Anthony C.; Yong, William; Geschwind, Daniel H.; Nakano, Ichiro; Goldman, Steven A.; Everson, Richard G.; Ellingson, Benjamin M.; Kornblum, Harley I.
In: Neuro-Oncology Advances, Vol. 6, No. 1, vdae005, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Single-nucleus expression characterization of non-enhancing region of recurrent high-grade glioma
AU - Patel, Kunal S.
AU - Tessema, Kaleab K.
AU - Kawaguchi, Riki
AU - Dudley, Lindsey
AU - Alvarado, Alvaro G.
AU - Muthukrishnan, Sree Deepthi
AU - Perryman, Travis
AU - Hagiwara, Akifumi
AU - Swarup, Vivek
AU - Liau, Linda M.
AU - Wang, Anthony C.
AU - Yong, William
AU - Geschwind, Daniel H.
AU - Nakano, Ichiro
AU - Goldman, Steven A.
AU - Everson, Richard G.
AU - Ellingson, Benjamin M.
AU - Kornblum, Harley I.
N1 - Publisher Copyright: © The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
PY - 2024
Y1 - 2024
N2 - Background. 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. Methods. We leveraged single-nucleus RNA sequencing on 15 specimens from recurrent high-grade gliomas (n = 5) to compare prospectively identified biopsy specimens acquired from CE and NE regions. Additionally, 24 CE and 22 NE biopsies had immunohistochemical staining to validate RNA findings. Results. Tumor cells in NE regions are enriched in neural progenitor cell-like cellular states, while CE regions are enriched in mesenchymal-like states. NE glioma cells have similar proportions of proliferative and putative glioma stem cells relative to CE regions, without significant differences in % Ki-67 staining.Tumor cells in NE regions exhibit upregulation of genes previously associated with lower grade gliomas. Our findings in recurrent GBM paralleled some of the findings in a re-analysis of a dataset from primary GBM. 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-nonpathological cell interactions. Conclusions. This comprehensive analysis illustrates differing tumor and nontumor 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. These findings also support the aggressive approach to resection of tumor-bearing NE regions.
AB - Background. 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. Methods. We leveraged single-nucleus RNA sequencing on 15 specimens from recurrent high-grade gliomas (n = 5) to compare prospectively identified biopsy specimens acquired from CE and NE regions. Additionally, 24 CE and 22 NE biopsies had immunohistochemical staining to validate RNA findings. Results. Tumor cells in NE regions are enriched in neural progenitor cell-like cellular states, while CE regions are enriched in mesenchymal-like states. NE glioma cells have similar proportions of proliferative and putative glioma stem cells relative to CE regions, without significant differences in % Ki-67 staining.Tumor cells in NE regions exhibit upregulation of genes previously associated with lower grade gliomas. Our findings in recurrent GBM paralleled some of the findings in a re-analysis of a dataset from primary GBM. 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-nonpathological cell interactions. Conclusions. This comprehensive analysis illustrates differing tumor and nontumor 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. These findings also support the aggressive approach to resection of tumor-bearing NE regions.
KW - contrast enhancing
KW - glioblastoma
KW - magnetic resonance imaging
KW - non-enhancing
U2 - 10.1093/noajnl/vdae005
DO - 10.1093/noajnl/vdae005
M3 - Journal article
AN - SCOPUS:85186078637
VL - 6
JO - Neuro-Oncology Advances
JF - Neuro-Oncology Advances
SN - 2632-2498
IS - 1
M1 - vdae005
ER -
ID: 384616965