Construction of Interferon-Gamma-Related Gene Signature to Characterize the Immune-Inflamed Phenotype of Glioblastoma and Predict Prognosis, Efficacy of Immunotherapy and Radiotherapy
Interferon-gamma (IFNG) has profound impacts on tumor-immune interaction and is of great clinical significance for multiple cancers. Exploring the role of IFNG in glioblastoma (GBM) may optimize the current treatment paradigm of this disease. Here, multi-dimensional data of 429 GBM samples were coll...
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| Format: | Article |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.729359/full |
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| author | Hang Ji Hang Ji Yixu Ba Yixu Ba Shuai Ma Shuai Ma Kuiyuan Hou Kuiyuan Hou Shan Mi Shan Mi Xin Gao Jiaqi Jin Jiaqi Jin Qin Gong Ting Liu Fang Wang Fang Wang Zhihui Liu Zhihui Liu Shupeng Li Jianyang Du Jianyang Du Shaoshan Hu Shaoshan Hu |
| author_facet | Hang Ji Hang Ji Yixu Ba Yixu Ba Shuai Ma Shuai Ma Kuiyuan Hou Kuiyuan Hou Shan Mi Shan Mi Xin Gao Jiaqi Jin Jiaqi Jin Qin Gong Ting Liu Fang Wang Fang Wang Zhihui Liu Zhihui Liu Shupeng Li Jianyang Du Jianyang Du Shaoshan Hu Shaoshan Hu |
| author_sort | Hang Ji |
| collection | DOAJ |
| description | Interferon-gamma (IFNG) has profound impacts on tumor-immune interaction and is of great clinical significance for multiple cancers. Exploring the role of IFNG in glioblastoma (GBM) may optimize the current treatment paradigm of this disease. Here, multi-dimensional data of 429 GBM samples were collected. Various bioinformatics algorithms were employed to establish a gene signature that characterizes immunological features, genomic alterations, and clinical characteristics associated with the IFNG response. In this way, a novel IFNG-related gene signature (IFNGrGS, including TGFBI, IL4I1, ACP5, and LUM) has been constructed and validated. Samples with increased IFNGrGS scores were characterized by increased neutrophil and macrophage infiltration and exuberant innate immune responses, while the activated adaptive immune response may be frustrated by multiple immunosuppressive mechanisms. Notably, the IFNG pathway as well as its antagonistic pathways including IL4, IL10, TGF-beta, and VEGF converged on the expression of immune checkpoints. Besides, gene mutations involved in the microenvironment were associated with the IFNGrGS-based stratification, where the heterogeneous prognostic significance of EGFR mutation may be related to the different degrees of IFNG response. Moreover, the IFNGrGS score had solid prognostic value and the potential to screen ICB and radiotherapy sensitive populations. Collectively, our study provided insights into the role of IFNG on the GBM immune microenvironment and offered feasible information for optimizing the treatment of GBM. |
| first_indexed | 2024-12-22T04:04:30Z |
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| id | doaj.art-615d72005b774b1c9a744c5fb3e534cc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T04:04:30Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-615d72005b774b1c9a744c5fb3e534cc2022-12-21T18:39:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.729359729359Construction of Interferon-Gamma-Related Gene Signature to Characterize the Immune-Inflamed Phenotype of Glioblastoma and Predict Prognosis, Efficacy of Immunotherapy and RadiotherapyHang Ji0Hang Ji1Yixu Ba2Yixu Ba3Shuai Ma4Shuai Ma5Kuiyuan Hou6Kuiyuan Hou7Shan Mi8Shan Mi9Xin Gao10Jiaqi Jin11Jiaqi Jin12Qin Gong13Ting Liu14Fang Wang15Fang Wang16Zhihui Liu17Zhihui Liu18Shupeng Li19Jianyang Du20Jianyang Du21Shaoshan Hu22Shaoshan Hu23Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaThe Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin, ChinaSchool of Life Sciences, Nanjing University, Nanjing, ChinaFaculty of Pharmacy, Harbin Medical University (DAQING), Daqing, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaThe Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaThe Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Emergency Medicine Center, Zhejiang Provincial People’s Hospital Affiliated to Hangzhou Medical College, Hangzhou, ChinaInterferon-gamma (IFNG) has profound impacts on tumor-immune interaction and is of great clinical significance for multiple cancers. Exploring the role of IFNG in glioblastoma (GBM) may optimize the current treatment paradigm of this disease. Here, multi-dimensional data of 429 GBM samples were collected. Various bioinformatics algorithms were employed to establish a gene signature that characterizes immunological features, genomic alterations, and clinical characteristics associated with the IFNG response. In this way, a novel IFNG-related gene signature (IFNGrGS, including TGFBI, IL4I1, ACP5, and LUM) has been constructed and validated. Samples with increased IFNGrGS scores were characterized by increased neutrophil and macrophage infiltration and exuberant innate immune responses, while the activated adaptive immune response may be frustrated by multiple immunosuppressive mechanisms. Notably, the IFNG pathway as well as its antagonistic pathways including IL4, IL10, TGF-beta, and VEGF converged on the expression of immune checkpoints. Besides, gene mutations involved in the microenvironment were associated with the IFNGrGS-based stratification, where the heterogeneous prognostic significance of EGFR mutation may be related to the different degrees of IFNG response. Moreover, the IFNGrGS score had solid prognostic value and the potential to screen ICB and radiotherapy sensitive populations. Collectively, our study provided insights into the role of IFNG on the GBM immune microenvironment and offered feasible information for optimizing the treatment of GBM.https://www.frontiersin.org/articles/10.3389/fimmu.2021.729359/fullglioblastomainterferon-gammatumor immune microenvironmentIFNG-related gene signatureanti-tumor immune responseimmune checkpoint blockade therapy |
| spellingShingle | Hang Ji Hang Ji Yixu Ba Yixu Ba Shuai Ma Shuai Ma Kuiyuan Hou Kuiyuan Hou Shan Mi Shan Mi Xin Gao Jiaqi Jin Jiaqi Jin Qin Gong Ting Liu Fang Wang Fang Wang Zhihui Liu Zhihui Liu Shupeng Li Jianyang Du Jianyang Du Shaoshan Hu Shaoshan Hu Construction of Interferon-Gamma-Related Gene Signature to Characterize the Immune-Inflamed Phenotype of Glioblastoma and Predict Prognosis, Efficacy of Immunotherapy and Radiotherapy Frontiers in Immunology glioblastoma interferon-gamma tumor immune microenvironment IFNG-related gene signature anti-tumor immune response immune checkpoint blockade therapy |
| title | Construction of Interferon-Gamma-Related Gene Signature to Characterize the Immune-Inflamed Phenotype of Glioblastoma and Predict Prognosis, Efficacy of Immunotherapy and Radiotherapy |
| title_full | Construction of Interferon-Gamma-Related Gene Signature to Characterize the Immune-Inflamed Phenotype of Glioblastoma and Predict Prognosis, Efficacy of Immunotherapy and Radiotherapy |
| title_fullStr | Construction of Interferon-Gamma-Related Gene Signature to Characterize the Immune-Inflamed Phenotype of Glioblastoma and Predict Prognosis, Efficacy of Immunotherapy and Radiotherapy |
| title_full_unstemmed | Construction of Interferon-Gamma-Related Gene Signature to Characterize the Immune-Inflamed Phenotype of Glioblastoma and Predict Prognosis, Efficacy of Immunotherapy and Radiotherapy |
| title_short | Construction of Interferon-Gamma-Related Gene Signature to Characterize the Immune-Inflamed Phenotype of Glioblastoma and Predict Prognosis, Efficacy of Immunotherapy and Radiotherapy |
| title_sort | construction of interferon gamma related gene signature to characterize the immune inflamed phenotype of glioblastoma and predict prognosis efficacy of immunotherapy and radiotherapy |
| topic | glioblastoma interferon-gamma tumor immune microenvironment IFNG-related gene signature anti-tumor immune response immune checkpoint blockade therapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.729359/full |
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