Development and Validation of an IDH1-Associated Immune Prognostic Signature for Diffuse Lower-Grade Glioma
A mutation in the isocitrate dehydrogenase 1 (IDH1) gene is the most common mutation in diffuse lower-grade gliomas (LGGs), and it is significantly related to the prognosis of LGGs. We aimed to explore the influence of the IDH1 mutation on the immune microenvironment and develop an IDH1-associated i...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.01310/full |
| _version_ | 1811296852086095872 |
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| author | Xiangyang Deng Dongdong Lin Bo Chen Xiaojia Zhang Xingxing Xu Zelin Yang Xuchao Shen Liang Yang Xiangqi Lu Hansong Sheng Bo Yin Nu Zhang Jian Lin |
| author_facet | Xiangyang Deng Dongdong Lin Bo Chen Xiaojia Zhang Xingxing Xu Zelin Yang Xuchao Shen Liang Yang Xiangqi Lu Hansong Sheng Bo Yin Nu Zhang Jian Lin |
| author_sort | Xiangyang Deng |
| collection | DOAJ |
| description | A mutation in the isocitrate dehydrogenase 1 (IDH1) gene is the most common mutation in diffuse lower-grade gliomas (LGGs), and it is significantly related to the prognosis of LGGs. We aimed to explore the influence of the IDH1 mutation on the immune microenvironment and develop an IDH1-associated immune prognostic signature (IPS) for predicting prognosis in LGGs. IDH1 mutation status and RNA expression were investigated in two different public cohorts. To develop an IPS, LASSO Cox analysis was conducted for immune-related genes that were differentially expressed between IDH1wt and IDH1mut LGG patients. Then, we systematically analyzed the influence of the IPS on the immune microenvironment. A total of 41 immune prognostic genes were identified based on the IDH1 mutation status. A four-gene IPS was established and LGG patients were effectively stratified into low- and high-risk groups in both the training and validation sets. Stratification analysis and multivariate Cox analysis revealed that the IPS was an independent prognostic factor. We also found that high-risk LGG patients had higher levels of infiltrating B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages and dendritic cells, and expressed higher levels of CTLA-4, PD-1 and TIM-3. Moreover, a novel nomogram model was established to estimate the overall survival in LGG patients. The current study provides novel insights into the LGG immune microenvironment and potential immunotherapies. The proposed IPS is a clinically promising biomarker that can be used to classify LGG patients into subgroups with distinct outcomes and immunophenotypes, with the potential to facilitate individualized management and improve prognosis. |
| first_indexed | 2024-04-13T05:54:39Z |
| format | Article |
| id | doaj.art-0e2d3a50c8dc4ddbbeacaa5f7257a55f |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T05:54:39Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-0e2d3a50c8dc4ddbbeacaa5f7257a55f2022-12-22T02:59:39ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-11-01910.3389/fonc.2019.01310479274Development and Validation of an IDH1-Associated Immune Prognostic Signature for Diffuse Lower-Grade GliomaXiangyang Deng0Dongdong Lin1Bo Chen2Xiaojia Zhang3Xingxing Xu4Zelin Yang5Xuchao Shen6Liang Yang7Xiangqi Lu8Hansong Sheng9Bo Yin10Nu Zhang11Jian Lin12Department of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, ChinaThe Second Clinical Medical College, Wenzhou Medical University, Wenzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, ChinaSchool of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, ChinaA mutation in the isocitrate dehydrogenase 1 (IDH1) gene is the most common mutation in diffuse lower-grade gliomas (LGGs), and it is significantly related to the prognosis of LGGs. We aimed to explore the influence of the IDH1 mutation on the immune microenvironment and develop an IDH1-associated immune prognostic signature (IPS) for predicting prognosis in LGGs. IDH1 mutation status and RNA expression were investigated in two different public cohorts. To develop an IPS, LASSO Cox analysis was conducted for immune-related genes that were differentially expressed between IDH1wt and IDH1mut LGG patients. Then, we systematically analyzed the influence of the IPS on the immune microenvironment. A total of 41 immune prognostic genes were identified based on the IDH1 mutation status. A four-gene IPS was established and LGG patients were effectively stratified into low- and high-risk groups in both the training and validation sets. Stratification analysis and multivariate Cox analysis revealed that the IPS was an independent prognostic factor. We also found that high-risk LGG patients had higher levels of infiltrating B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages and dendritic cells, and expressed higher levels of CTLA-4, PD-1 and TIM-3. Moreover, a novel nomogram model was established to estimate the overall survival in LGG patients. The current study provides novel insights into the LGG immune microenvironment and potential immunotherapies. The proposed IPS is a clinically promising biomarker that can be used to classify LGG patients into subgroups with distinct outcomes and immunophenotypes, with the potential to facilitate individualized management and improve prognosis.https://www.frontiersin.org/article/10.3389/fonc.2019.01310/fulllower-grade gliomaIDH1mutationimmune prognostic signaturenomogram |
| spellingShingle | Xiangyang Deng Dongdong Lin Bo Chen Xiaojia Zhang Xingxing Xu Zelin Yang Xuchao Shen Liang Yang Xiangqi Lu Hansong Sheng Bo Yin Nu Zhang Jian Lin Development and Validation of an IDH1-Associated Immune Prognostic Signature for Diffuse Lower-Grade Glioma Frontiers in Oncology lower-grade glioma IDH1 mutation immune prognostic signature nomogram |
| title | Development and Validation of an IDH1-Associated Immune Prognostic Signature for Diffuse Lower-Grade Glioma |
| title_full | Development and Validation of an IDH1-Associated Immune Prognostic Signature for Diffuse Lower-Grade Glioma |
| title_fullStr | Development and Validation of an IDH1-Associated Immune Prognostic Signature for Diffuse Lower-Grade Glioma |
| title_full_unstemmed | Development and Validation of an IDH1-Associated Immune Prognostic Signature for Diffuse Lower-Grade Glioma |
| title_short | Development and Validation of an IDH1-Associated Immune Prognostic Signature for Diffuse Lower-Grade Glioma |
| title_sort | development and validation of an idh1 associated immune prognostic signature for diffuse lower grade glioma |
| topic | lower-grade glioma IDH1 mutation immune prognostic signature nomogram |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.01310/full |
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