A Novel Prognostic Tool for Glioma Based on Enhancer RNA-Regulated Immune Genes
Background: Gliomas are the most malignant tumors of the nervous system. Even though their survival outcome is closely affected by immune-related genes (IRGs) in the tumor microenvironment (TME), the corresponding regulatory mechanism remains poorly characterized.Methods: Specific enhancer RNAs (eRN...
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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.798445/full |
| _version_ | 1798015521832042496 |
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| author | Wei Tian Kegong Chen Guangcan Yan Xinhao Han Yanlong Liu Qiuju Zhang Meina Liu |
| author_facet | Wei Tian Kegong Chen Guangcan Yan Xinhao Han Yanlong Liu Qiuju Zhang Meina Liu |
| author_sort | Wei Tian |
| collection | DOAJ |
| description | Background: Gliomas are the most malignant tumors of the nervous system. Even though their survival outcome is closely affected by immune-related genes (IRGs) in the tumor microenvironment (TME), the corresponding regulatory mechanism remains poorly characterized.Methods: Specific enhancer RNAs (eRNAs) can be found in tumors, where they control downstream genes. The present study aimed to identify eRNA-regulated IRGs, evaluate their influence on the TME, and use them to construct a novel prognostic model for gliomas.Results: Thirteen target genes (ADCYAP1R1, BMP2, BMPR1A, CD4, DDX17, ELN, FGF13, MAPT, PDIA2, PSMB8, PTPN6, SEMA6C, and SSTR5) were identified and integrated into a comprehensive risk signature, which distinguished two risk subclasses. Discrepancies between these subclasses were compared to explore potential mechanisms attributed to eRNA-regulated genes, including immune cell infiltration, clinicopathological features, survival outcomes, and chemotherapeutic drug sensitivity. Furthermore, the risk signature was used to construct a prognostic tool that was evaluated by calibration curve, clinical utility, Harrell’s concordance index (0.87; 95% CI: 0.84–0.90), and time-dependent receiver operator characteristic curves (AUCs: 0.93 and 0.89 at 3 and 5 years, respectively). The strong reliability and robustness of the established prognostic tool were validated in another independent cohort. Finally, potential subtypes were explored in patients with grade III tumors.Conclusion: Overall, eRNAs were associated with immune-related dysfunctions in the TME. Targeting of IRGs regulated by eRNAs could improve immunotherapeutic/therapeutic outcomes. |
| first_indexed | 2024-04-11T15:34:42Z |
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| id | doaj.art-7995a5c1e66a447398fbf5b292ee2345 |
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| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-11T15:34:42Z |
| publishDate | 2022-01-01 |
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| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-7995a5c1e66a447398fbf5b292ee23452022-12-22T04:16:02ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-01-01910.3389/fcell.2021.798445798445A Novel Prognostic Tool for Glioma Based on Enhancer RNA-Regulated Immune GenesWei Tian0Kegong Chen1Guangcan Yan2Xinhao Han3Yanlong Liu4Qiuju Zhang5Meina Liu6Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin, ChinaDepartment of Cardio-Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Biostatistics, School of Public Health, Harbin Medical University, Harbin, ChinaDepartment of Biostatistics, School of Public Health, Harbin Medical University, Harbin, ChinaDepartment of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Biostatistics, School of Public Health, Harbin Medical University, Harbin, ChinaDepartment of Biostatistics, School of Public Health, Harbin Medical University, Harbin, ChinaBackground: Gliomas are the most malignant tumors of the nervous system. Even though their survival outcome is closely affected by immune-related genes (IRGs) in the tumor microenvironment (TME), the corresponding regulatory mechanism remains poorly characterized.Methods: Specific enhancer RNAs (eRNAs) can be found in tumors, where they control downstream genes. The present study aimed to identify eRNA-regulated IRGs, evaluate their influence on the TME, and use them to construct a novel prognostic model for gliomas.Results: Thirteen target genes (ADCYAP1R1, BMP2, BMPR1A, CD4, DDX17, ELN, FGF13, MAPT, PDIA2, PSMB8, PTPN6, SEMA6C, and SSTR5) were identified and integrated into a comprehensive risk signature, which distinguished two risk subclasses. Discrepancies between these subclasses were compared to explore potential mechanisms attributed to eRNA-regulated genes, including immune cell infiltration, clinicopathological features, survival outcomes, and chemotherapeutic drug sensitivity. Furthermore, the risk signature was used to construct a prognostic tool that was evaluated by calibration curve, clinical utility, Harrell’s concordance index (0.87; 95% CI: 0.84–0.90), and time-dependent receiver operator characteristic curves (AUCs: 0.93 and 0.89 at 3 and 5 years, respectively). The strong reliability and robustness of the established prognostic tool were validated in another independent cohort. Finally, potential subtypes were explored in patients with grade III tumors.Conclusion: Overall, eRNAs were associated with immune-related dysfunctions in the TME. Targeting of IRGs regulated by eRNAs could improve immunotherapeutic/therapeutic outcomes.https://www.frontiersin.org/articles/10.3389/fcell.2021.798445/fullenhancer RNAsuper enhancer RNAimmune-related geneprognosisglomas |
| spellingShingle | Wei Tian Kegong Chen Guangcan Yan Xinhao Han Yanlong Liu Qiuju Zhang Meina Liu A Novel Prognostic Tool for Glioma Based on Enhancer RNA-Regulated Immune Genes Frontiers in Cell and Developmental Biology enhancer RNA super enhancer RNA immune-related gene prognosis glomas |
| title | A Novel Prognostic Tool for Glioma Based on Enhancer RNA-Regulated Immune Genes |
| title_full | A Novel Prognostic Tool for Glioma Based on Enhancer RNA-Regulated Immune Genes |
| title_fullStr | A Novel Prognostic Tool for Glioma Based on Enhancer RNA-Regulated Immune Genes |
| title_full_unstemmed | A Novel Prognostic Tool for Glioma Based on Enhancer RNA-Regulated Immune Genes |
| title_short | A Novel Prognostic Tool for Glioma Based on Enhancer RNA-Regulated Immune Genes |
| title_sort | novel prognostic tool for glioma based on enhancer rna regulated immune genes |
| topic | enhancer RNA super enhancer RNA immune-related gene prognosis glomas |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.798445/full |
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