Fc gamma receptor IIb in tumor-associated macrophages and dendritic cells drives poor prognosis of recurrent glioblastoma through immune-associated signaling pathways
Background: Among central nervous system tumors, glioblastoma (GBM) is considered to be the most destructive malignancy. Recurrence is one of the most fatal aspects of GBM. However, the driver molecules that trigger GBM recurrence are currently unclear.Methods: The mRNA expression data and clinical...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.1046008/full |
| _version_ | 1828070511664431104 |
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| author | Xiong Jin Jianlei Kang Qing Lu Shuang-Lei Guo Meichen Liu Yue Zhang Can Cui Hong-Lin Liu Xin Xu Jinlong Yin |
| author_facet | Xiong Jin Jianlei Kang Qing Lu Shuang-Lei Guo Meichen Liu Yue Zhang Can Cui Hong-Lin Liu Xin Xu Jinlong Yin |
| author_sort | Xiong Jin |
| collection | DOAJ |
| description | Background: Among central nervous system tumors, glioblastoma (GBM) is considered to be the most destructive malignancy. Recurrence is one of the most fatal aspects of GBM. However, the driver molecules that trigger GBM recurrence are currently unclear.Methods: The mRNA expression data and clinical information of GBM and normal tissues were collected from the Chinese Glioma Genome Atlas The Cancer Genome Atlas (TCGA), and REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) cohorts. The DESeq2 R package was used to identify the differentially expressed genes between primary and recurrent GBM. ClueGO, Kyoto Encyclopedia of Genes and Genomes (KEGG), Biological Process in Gene ontology (GO-BP), and the Protein ANalysis THrough Evolutionary Relationships (PANTHER) pathway analyses were performed to explore the enriched signaling pathways in upregulated DEGs in recurrent GBM. A gene list that contained potential oncogenes that showed a significant negative correlation with patient survival from The Cancer Genome Atlas was used to further screen driver candidates for recurrent GBM. Univariate Cox proportional hazards regression analyses were used to investigate the risk score for the mRNA expression of the candidates. Single-cell RNA sequencing (scRNA-Seq) analyses were used to determine the cell type-specific distribution of Fc gamma receptor II b (FcγRIIb) in GBM. Immunohistochemistry (IHC) was used to confirm the FcγRIIb-positive cell populations in primary and paired recurrent GBM.Results: Through DEG analysis and overlap analysis, a total of 10 genes that are upregulated in recurrent GBM were screened. Using validation databases, FcγRIIb was identified from the 10 candidates that may serve as a driver for recurrent GBM. FCGR2B expression, not mutation, further showed a highly negative correlation with the poor prognosis of patients with recurrent GBM. Furthermore, scRNA-Seq analyses revealed that tumor-associated macrophage- and dendritic cell-specific FCGR2B was expressed. Moreover, FcγRIIb also showed a strong positive correlation coefficient with major immune-associated signaling pathways. In clinical specimens, FcγRIIb-positive cell populations were higher in recurrent GBM than in primary GBM.Conclusion: This study provides novel insights into the role of FcγRIIb in recurrent GBM and a promising strategy for treatment as an immune therapeutic target. |
| first_indexed | 2024-04-11T00:37:49Z |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T00:37:49Z |
| publishDate | 2023-01-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-2e5542491a784e8db4fba5bfc26856ae2023-01-06T13:36:53ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-01-011310.3389/fgene.2022.10460081046008Fc gamma receptor IIb in tumor-associated macrophages and dendritic cells drives poor prognosis of recurrent glioblastoma through immune-associated signaling pathwaysXiong Jin0Jianlei Kang1Qing Lu2Shuang-Lei Guo3Meichen Liu4Yue Zhang5Can Cui6Hong-Lin Liu7Xin Xu8Jinlong Yin9Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng, ChinaDepartment of Neurosurgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, ChinaPlastic Surgery Department of the First Affiliated Hospital of Henan University, Kaifeng, ChinaDepartment of Neurosurgery, Huaihe Hospital of Henan University, Kaifeng, ChinaHenan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng, ChinaHenan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng, ChinaHenan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng, ChinaDepartment of Neurosurgery, Huaihe Hospital of Henan University, Kaifeng, ChinaDepartment of Neurosurgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, ChinaHenan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng, ChinaBackground: Among central nervous system tumors, glioblastoma (GBM) is considered to be the most destructive malignancy. Recurrence is one of the most fatal aspects of GBM. However, the driver molecules that trigger GBM recurrence are currently unclear.Methods: The mRNA expression data and clinical information of GBM and normal tissues were collected from the Chinese Glioma Genome Atlas The Cancer Genome Atlas (TCGA), and REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) cohorts. The DESeq2 R package was used to identify the differentially expressed genes between primary and recurrent GBM. ClueGO, Kyoto Encyclopedia of Genes and Genomes (KEGG), Biological Process in Gene ontology (GO-BP), and the Protein ANalysis THrough Evolutionary Relationships (PANTHER) pathway analyses were performed to explore the enriched signaling pathways in upregulated DEGs in recurrent GBM. A gene list that contained potential oncogenes that showed a significant negative correlation with patient survival from The Cancer Genome Atlas was used to further screen driver candidates for recurrent GBM. Univariate Cox proportional hazards regression analyses were used to investigate the risk score for the mRNA expression of the candidates. Single-cell RNA sequencing (scRNA-Seq) analyses were used to determine the cell type-specific distribution of Fc gamma receptor II b (FcγRIIb) in GBM. Immunohistochemistry (IHC) was used to confirm the FcγRIIb-positive cell populations in primary and paired recurrent GBM.Results: Through DEG analysis and overlap analysis, a total of 10 genes that are upregulated in recurrent GBM were screened. Using validation databases, FcγRIIb was identified from the 10 candidates that may serve as a driver for recurrent GBM. FCGR2B expression, not mutation, further showed a highly negative correlation with the poor prognosis of patients with recurrent GBM. Furthermore, scRNA-Seq analyses revealed that tumor-associated macrophage- and dendritic cell-specific FCGR2B was expressed. Moreover, FcγRIIb also showed a strong positive correlation coefficient with major immune-associated signaling pathways. In clinical specimens, FcγRIIb-positive cell populations were higher in recurrent GBM than in primary GBM.Conclusion: This study provides novel insights into the role of FcγRIIb in recurrent GBM and a promising strategy for treatment as an immune therapeutic target.https://www.frontiersin.org/articles/10.3389/fgene.2022.1046008/fullrecurrent glioblastomaFcgr2btumor-associated macrophagedendritic cellimmune-associated signaling pathway |
| spellingShingle | Xiong Jin Jianlei Kang Qing Lu Shuang-Lei Guo Meichen Liu Yue Zhang Can Cui Hong-Lin Liu Xin Xu Jinlong Yin Fc gamma receptor IIb in tumor-associated macrophages and dendritic cells drives poor prognosis of recurrent glioblastoma through immune-associated signaling pathways Frontiers in Genetics recurrent glioblastoma Fcgr2b tumor-associated macrophage dendritic cell immune-associated signaling pathway |
| title | Fc gamma receptor IIb in tumor-associated macrophages and dendritic cells drives poor prognosis of recurrent glioblastoma through immune-associated signaling pathways |
| title_full | Fc gamma receptor IIb in tumor-associated macrophages and dendritic cells drives poor prognosis of recurrent glioblastoma through immune-associated signaling pathways |
| title_fullStr | Fc gamma receptor IIb in tumor-associated macrophages and dendritic cells drives poor prognosis of recurrent glioblastoma through immune-associated signaling pathways |
| title_full_unstemmed | Fc gamma receptor IIb in tumor-associated macrophages and dendritic cells drives poor prognosis of recurrent glioblastoma through immune-associated signaling pathways |
| title_short | Fc gamma receptor IIb in tumor-associated macrophages and dendritic cells drives poor prognosis of recurrent glioblastoma through immune-associated signaling pathways |
| title_sort | fc gamma receptor iib in tumor associated macrophages and dendritic cells drives poor prognosis of recurrent glioblastoma through immune associated signaling pathways |
| topic | recurrent glioblastoma Fcgr2b tumor-associated macrophage dendritic cell immune-associated signaling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1046008/full |
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