Characterization of tumor-associated reactive astrocytes in gliomas by single-cell and bulk tumor sequencing
ObjectiveAstrocytes constitute approximately 30% of cells in gliomas and play important roles in synapse construction and survival. Recently, JAK/STAT pathway activation associated with a new type of astrocyte was reported. However, the implications of these tumor-associated reactive astrocytes (TAR...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1193844/full |
| _version_ | 1797798483725385728 |
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| author | Chuan-bao Zhang Chuan-bao Zhang Zhi-liang Wang Zhi-liang Wang Han-jie Liu Han-jie Liu Zheng Wang Zheng Wang Wang Jia Wang Jia |
| author_facet | Chuan-bao Zhang Chuan-bao Zhang Zhi-liang Wang Zhi-liang Wang Han-jie Liu Han-jie Liu Zheng Wang Zheng Wang Wang Jia Wang Jia |
| author_sort | Chuan-bao Zhang |
| collection | DOAJ |
| description | ObjectiveAstrocytes constitute approximately 30% of cells in gliomas and play important roles in synapse construction and survival. Recently, JAK/STAT pathway activation associated with a new type of astrocyte was reported. However, the implications of these tumor-associated reactive astrocytes (TARAs) in glioma are not known.MethodsWe comprehensively assessed TARAs in gliomas, both in single cells and at the bulk tumor level, by analyzing five independent datasets. First, we analyzed two single-cell RNA sequencing datasets of 35,563 cells from 23 patients to estimate the infiltration level of TARAs in gliomas. Second, we collected clinical information and genomic and transcriptomic data of 1,379 diffuse astrocytoma and glioblastoma samples from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas datasets to evaluate the genomic, transcriptomic and clinical characteristics of TARA infiltration. Third, we downloaded expression profiles of recurrent glioblastoma samples from patients receiving PD-1 inhibitors to analyze the predictive value of TARAs for immune checkpoint inhibition.ResultsSingle-cell RNA sequencing data showed TARAs were abundant in the glioma micro-environment (15.7% in the CGGA dataset and 9.1% in the Gene Expression Omnibus GSE141383 dataset, respectively). Bulk tumor sequencing data showed that the extent of TARA infiltration was highly associated with major clinical and molecular features of astrocytic gliomas. Patients with more TARA infiltration were more likely to have MUC16, FLG, and PICK3A mutations, chromosome 9p21.3, 10q23.3, and 13q14.2 deletions and 7p11.2 amplification. Gene Ontology analysis revealed that the high level of astrocyte infiltration was characterized by immune and oncogenic pathways, such as the inflammatory response, positive regulation of the JAK–STAT cascade, positive regulation of NIK/NF-kappa B signaling and the tumor necrosis factor biosynthetic process. Patients with greater TARA infiltration showed inferior prognosis. Meanwhile, the extent of reactive astrocyte infiltration exhibited a predictive value for recurrent glioblastoma patients undergoing anti-PD-1 immune therapy.ConclusionTARA infiltration might promote glioma tumor progression and can be used as a diagnostic, predictive and prognostic marker in gliomas. Prevention of TARA infiltration might be a new therapeutic strategy for glioma. |
| first_indexed | 2024-03-13T04:05:26Z |
| format | Article |
| id | doaj.art-919900afbf954840b5a3b0b7a5c620dd |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-03-13T04:05:26Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-919900afbf954840b5a3b0b7a5c620dd2023-06-21T08:21:20ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-06-011410.3389/fneur.2023.11938441193844Characterization of tumor-associated reactive astrocytes in gliomas by single-cell and bulk tumor sequencingChuan-bao Zhang0Chuan-bao Zhang1Zhi-liang Wang2Zhi-liang Wang3Han-jie Liu4Han-jie Liu5Zheng Wang6Zheng Wang7Wang Jia8Wang Jia9Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaThe Chinese Glioma Genome Atlas (CGGA) Project, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaThe Chinese Glioma Genome Atlas (CGGA) Project, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaThe Chinese Glioma Genome Atlas (CGGA) Project, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaThe Chinese Glioma Genome Atlas (CGGA) Project, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaThe Chinese Glioma Genome Atlas (CGGA) Project, Beijing, ChinaObjectiveAstrocytes constitute approximately 30% of cells in gliomas and play important roles in synapse construction and survival. Recently, JAK/STAT pathway activation associated with a new type of astrocyte was reported. However, the implications of these tumor-associated reactive astrocytes (TARAs) in glioma are not known.MethodsWe comprehensively assessed TARAs in gliomas, both in single cells and at the bulk tumor level, by analyzing five independent datasets. First, we analyzed two single-cell RNA sequencing datasets of 35,563 cells from 23 patients to estimate the infiltration level of TARAs in gliomas. Second, we collected clinical information and genomic and transcriptomic data of 1,379 diffuse astrocytoma and glioblastoma samples from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas datasets to evaluate the genomic, transcriptomic and clinical characteristics of TARA infiltration. Third, we downloaded expression profiles of recurrent glioblastoma samples from patients receiving PD-1 inhibitors to analyze the predictive value of TARAs for immune checkpoint inhibition.ResultsSingle-cell RNA sequencing data showed TARAs were abundant in the glioma micro-environment (15.7% in the CGGA dataset and 9.1% in the Gene Expression Omnibus GSE141383 dataset, respectively). Bulk tumor sequencing data showed that the extent of TARA infiltration was highly associated with major clinical and molecular features of astrocytic gliomas. Patients with more TARA infiltration were more likely to have MUC16, FLG, and PICK3A mutations, chromosome 9p21.3, 10q23.3, and 13q14.2 deletions and 7p11.2 amplification. Gene Ontology analysis revealed that the high level of astrocyte infiltration was characterized by immune and oncogenic pathways, such as the inflammatory response, positive regulation of the JAK–STAT cascade, positive regulation of NIK/NF-kappa B signaling and the tumor necrosis factor biosynthetic process. Patients with greater TARA infiltration showed inferior prognosis. Meanwhile, the extent of reactive astrocyte infiltration exhibited a predictive value for recurrent glioblastoma patients undergoing anti-PD-1 immune therapy.ConclusionTARA infiltration might promote glioma tumor progression and can be used as a diagnostic, predictive and prognostic marker in gliomas. Prevention of TARA infiltration might be a new therapeutic strategy for glioma.https://www.frontiersin.org/articles/10.3389/fneur.2023.1193844/fullreactive astrocytesgliomamolecular and genomic featuresimmunotherapysequencing |
| spellingShingle | Chuan-bao Zhang Chuan-bao Zhang Zhi-liang Wang Zhi-liang Wang Han-jie Liu Han-jie Liu Zheng Wang Zheng Wang Wang Jia Wang Jia Characterization of tumor-associated reactive astrocytes in gliomas by single-cell and bulk tumor sequencing Frontiers in Neurology reactive astrocytes glioma molecular and genomic features immunotherapy sequencing |
| title | Characterization of tumor-associated reactive astrocytes in gliomas by single-cell and bulk tumor sequencing |
| title_full | Characterization of tumor-associated reactive astrocytes in gliomas by single-cell and bulk tumor sequencing |
| title_fullStr | Characterization of tumor-associated reactive astrocytes in gliomas by single-cell and bulk tumor sequencing |
| title_full_unstemmed | Characterization of tumor-associated reactive astrocytes in gliomas by single-cell and bulk tumor sequencing |
| title_short | Characterization of tumor-associated reactive astrocytes in gliomas by single-cell and bulk tumor sequencing |
| title_sort | characterization of tumor associated reactive astrocytes in gliomas by single cell and bulk tumor sequencing |
| topic | reactive astrocytes glioma molecular and genomic features immunotherapy sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1193844/full |
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