Combined bulk RNA-seq and single-cell RNA-seq identifies a necroptosis-related prognostic signature associated with inhibitory immune microenvironment in glioma
Necroptosis is a programmed cell death playing a significant role in cancer. Although necroptosis has been related to tumor immune environment (TIME) remodeling and cancer prognosis, however, the role of necroptosis-related genes (NRGs) in glioma is still elusive. In this study, a total of 159 NRGs...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1013094/full |
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| author | Sicheng Wan Sicheng Wan Ulrich Aymard Ekomi Moure Ulrich Aymard Ekomi Moure Ruochen Liu Ruochen Liu Chaolong Liu Chaolong Liu Kun Wang Kun Wang Longfei Deng Longfei Deng Ping Liang Hongjuan Cui Hongjuan Cui |
| author_facet | Sicheng Wan Sicheng Wan Ulrich Aymard Ekomi Moure Ulrich Aymard Ekomi Moure Ruochen Liu Ruochen Liu Chaolong Liu Chaolong Liu Kun Wang Kun Wang Longfei Deng Longfei Deng Ping Liang Hongjuan Cui Hongjuan Cui |
| author_sort | Sicheng Wan |
| collection | DOAJ |
| description | Necroptosis is a programmed cell death playing a significant role in cancer. Although necroptosis has been related to tumor immune environment (TIME) remodeling and cancer prognosis, however, the role of necroptosis-related genes (NRGs) in glioma is still elusive. In this study, a total of 159 NRGs were obtained, and parameters such as mutation rate, copy number variation (CNV), and relative expression level were assessed. Then, we constructed an 18-NRGs-based necroptosis-related signature (NRS) in the TCGA dataset, which could predict the patient’s prognosis and was validated in two external CGGA datasets. We also explored the correlation between NRS and glioma TIME, chemotherapy sensitivity, and certain immunotherapy-related factors. The two necroptosis-related subtypes were discovered and could also distinguish the patients' prognosis. Through the glioblastoma (GBM) scRNA-seq data analysis, NRGs’ expression levels in different GBM patient tissue cell subsets were investigated and the relative necroptosis status of different cell subsets was assessed, with the microglia score culminating among all. Moreover, we found a high infiltration level of immunosuppressive cells in glioma TIME, which was associated with poor prognosis in the high-NRS glioma patient group. Finally, the necroptosis suppressor CASP8 exhibited a high expression in glioma and was associated with poor prognosis. Subsequent experiments were performed in human glioma cell lines and patients' tissue specimens to verify the bioinformatic analytic findings about CASP8. Altogether, this study provides comprehensive evidence revealing a prognostic value of NRGs in glioma, which is associated with TIME regulation. |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T08:01:59Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-d4ba373b37134bf6a874da543567e1702022-12-22T04:35:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10130941013094Combined bulk RNA-seq and single-cell RNA-seq identifies a necroptosis-related prognostic signature associated with inhibitory immune microenvironment in gliomaSicheng Wan0Sicheng Wan1Ulrich Aymard Ekomi Moure2Ulrich Aymard Ekomi Moure3Ruochen Liu4Ruochen Liu5Chaolong Liu6Chaolong Liu7Kun Wang8Kun Wang9Longfei Deng10Longfei Deng11Ping Liang12Hongjuan Cui13Hongjuan Cui14The State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing, ChinaCancer Center, Medical Research Institute, Southwest University, Chongqing, ChinaCancer Center, Medical Research Institute, Southwest University, Chongqing, ChinaThe Ninth People’s Hospital of Chongqing, Affiliated Hospital of Southwest University, Chongqing, ChinaThe State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing, ChinaCancer Center, Medical Research Institute, Southwest University, Chongqing, ChinaThe State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing, ChinaCancer Center, Medical Research Institute, Southwest University, Chongqing, ChinaThe State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing, ChinaCancer Center, Medical Research Institute, Southwest University, Chongqing, ChinaThe State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing, ChinaCancer Center, Medical Research Institute, Southwest University, Chongqing, ChinaDepartment of Neurosurgery, Chongqing Children’s Hospital, Chongqing, ChinaThe State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing, ChinaCancer Center, Medical Research Institute, Southwest University, Chongqing, ChinaNecroptosis is a programmed cell death playing a significant role in cancer. Although necroptosis has been related to tumor immune environment (TIME) remodeling and cancer prognosis, however, the role of necroptosis-related genes (NRGs) in glioma is still elusive. In this study, a total of 159 NRGs were obtained, and parameters such as mutation rate, copy number variation (CNV), and relative expression level were assessed. Then, we constructed an 18-NRGs-based necroptosis-related signature (NRS) in the TCGA dataset, which could predict the patient’s prognosis and was validated in two external CGGA datasets. We also explored the correlation between NRS and glioma TIME, chemotherapy sensitivity, and certain immunotherapy-related factors. The two necroptosis-related subtypes were discovered and could also distinguish the patients' prognosis. Through the glioblastoma (GBM) scRNA-seq data analysis, NRGs’ expression levels in different GBM patient tissue cell subsets were investigated and the relative necroptosis status of different cell subsets was assessed, with the microglia score culminating among all. Moreover, we found a high infiltration level of immunosuppressive cells in glioma TIME, which was associated with poor prognosis in the high-NRS glioma patient group. Finally, the necroptosis suppressor CASP8 exhibited a high expression in glioma and was associated with poor prognosis. Subsequent experiments were performed in human glioma cell lines and patients' tissue specimens to verify the bioinformatic analytic findings about CASP8. Altogether, this study provides comprehensive evidence revealing a prognostic value of NRGs in glioma, which is associated with TIME regulation.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1013094/fullnecroptosis-related genenecroptosis-related prognostic signaturegliomatumor immune microenvironmentsingle cell RNA seq |
| spellingShingle | Sicheng Wan Sicheng Wan Ulrich Aymard Ekomi Moure Ulrich Aymard Ekomi Moure Ruochen Liu Ruochen Liu Chaolong Liu Chaolong Liu Kun Wang Kun Wang Longfei Deng Longfei Deng Ping Liang Hongjuan Cui Hongjuan Cui Combined bulk RNA-seq and single-cell RNA-seq identifies a necroptosis-related prognostic signature associated with inhibitory immune microenvironment in glioma Frontiers in Immunology necroptosis-related gene necroptosis-related prognostic signature glioma tumor immune microenvironment single cell RNA seq |
| title | Combined bulk RNA-seq and single-cell RNA-seq identifies a necroptosis-related prognostic signature associated with inhibitory immune microenvironment in glioma |
| title_full | Combined bulk RNA-seq and single-cell RNA-seq identifies a necroptosis-related prognostic signature associated with inhibitory immune microenvironment in glioma |
| title_fullStr | Combined bulk RNA-seq and single-cell RNA-seq identifies a necroptosis-related prognostic signature associated with inhibitory immune microenvironment in glioma |
| title_full_unstemmed | Combined bulk RNA-seq and single-cell RNA-seq identifies a necroptosis-related prognostic signature associated with inhibitory immune microenvironment in glioma |
| title_short | Combined bulk RNA-seq and single-cell RNA-seq identifies a necroptosis-related prognostic signature associated with inhibitory immune microenvironment in glioma |
| title_sort | combined bulk rna seq and single cell rna seq identifies a necroptosis related prognostic signature associated with inhibitory immune microenvironment in glioma |
| topic | necroptosis-related gene necroptosis-related prognostic signature glioma tumor immune microenvironment single cell RNA seq |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1013094/full |
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