Transcriptional Networks Identify BRPF1 as a Potential Drug Target Based on Inflammatory Signature in Primary Lower-Grade Gliomas
Gliomas are the most common tumors of the central nervous system and are classified into grades I-IV based on their histological characteristics. Lower-grade gliomas (LGG) can be divided into grade II diffuse low-grade gliomas and grade III moderate gliomas and have a relatively good prognosis. Howe...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.766656/full |
| _version_ | 1818893504083918848 |
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| author | Mingyang Xia Huiyao Chen Tong Chen Ping Xue Xinran Dong Yifeng Lin Duan Ma Wenhao Zhou Wenhao Zhou Wenhao Zhou Wei Shi Hao Li |
| author_facet | Mingyang Xia Huiyao Chen Tong Chen Ping Xue Xinran Dong Yifeng Lin Duan Ma Wenhao Zhou Wenhao Zhou Wenhao Zhou Wei Shi Hao Li |
| author_sort | Mingyang Xia |
| collection | DOAJ |
| description | Gliomas are the most common tumors of the central nervous system and are classified into grades I-IV based on their histological characteristics. Lower-grade gliomas (LGG) can be divided into grade II diffuse low-grade gliomas and grade III moderate gliomas and have a relatively good prognosis. However, LGG often develops into high-grade glioma within a few years. This study aimed to construct and identify the prognostic value of an inflammatory signature and discover potential drug targets for primary LGG. We first screened differentially expressed genes in primary LGG (TCGA) compared with normal brain tissue (GTEx) that overlapped with inflammation-related genes from MSigDB. After survival analysis, nine genes were selected to construct an inflammatory signature. LGG patients with a high inflammatory signature score had a poor prognosis, and the inflammatory signature was a strong independent prognostic factor in both the training cohort (TCGA) and validation cohort (CGGA). Compared with the low-inflammatory signature group, differentially expressed genes in the high-inflammatory signature group were mainly enriched in immune-related signaling pathways, which is consistent with the distribution of immune cells in the high- and low-inflammatory signature groups. Integrating driver genes, upregulated genes and drug targets data, bromodomain and PHD finger-containing protein 1 (BRPF1) was selected as a potential drug target. Inhibition of BRPF1 function or knockdown of BRPF1 expression attenuated glioma cell proliferation and colony formation. |
| first_indexed | 2024-12-19T18:13:39Z |
| format | Article |
| id | doaj.art-0a4de17a68684562901dd2bb55154a33 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-19T18:13:39Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-0a4de17a68684562901dd2bb55154a332022-12-21T20:11:12ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-12-011110.3389/fonc.2021.766656766656Transcriptional Networks Identify BRPF1 as a Potential Drug Target Based on Inflammatory Signature in Primary Lower-Grade GliomasMingyang Xia0Huiyao Chen1Tong Chen2Ping Xue3Xinran Dong4Yifeng Lin5Duan Ma6Wenhao Zhou7Wenhao Zhou8Wenhao Zhou9Wei Shi10Hao Li11Key Laboratory of Birth Defects, Children’s Hospital of Fudan University, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaKey Laboratory of Birth Defects, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Children’s Hospital of Fudan University, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, Shanghai, ChinaKey Laboratory of Birth Defects, Children’s Hospital of Fudan University, Shanghai, ChinaKey Laboratory of Neonatal Diseases, Division of Neonatology, Children’s Hospital of Fudan University, Ministry of Health, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, Shanghai, ChinaKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Children’s Hospital of Fudan University, Shanghai, ChinaGliomas are the most common tumors of the central nervous system and are classified into grades I-IV based on their histological characteristics. Lower-grade gliomas (LGG) can be divided into grade II diffuse low-grade gliomas and grade III moderate gliomas and have a relatively good prognosis. However, LGG often develops into high-grade glioma within a few years. This study aimed to construct and identify the prognostic value of an inflammatory signature and discover potential drug targets for primary LGG. We first screened differentially expressed genes in primary LGG (TCGA) compared with normal brain tissue (GTEx) that overlapped with inflammation-related genes from MSigDB. After survival analysis, nine genes were selected to construct an inflammatory signature. LGG patients with a high inflammatory signature score had a poor prognosis, and the inflammatory signature was a strong independent prognostic factor in both the training cohort (TCGA) and validation cohort (CGGA). Compared with the low-inflammatory signature group, differentially expressed genes in the high-inflammatory signature group were mainly enriched in immune-related signaling pathways, which is consistent with the distribution of immune cells in the high- and low-inflammatory signature groups. Integrating driver genes, upregulated genes and drug targets data, bromodomain and PHD finger-containing protein 1 (BRPF1) was selected as a potential drug target. Inhibition of BRPF1 function or knockdown of BRPF1 expression attenuated glioma cell proliferation and colony formation.https://www.frontiersin.org/articles/10.3389/fonc.2021.766656/fulllower-grade gliomasinflammatory signatureprognostic markerdrug targetsBRPF1 |
| spellingShingle | Mingyang Xia Huiyao Chen Tong Chen Ping Xue Xinran Dong Yifeng Lin Duan Ma Wenhao Zhou Wenhao Zhou Wenhao Zhou Wei Shi Hao Li Transcriptional Networks Identify BRPF1 as a Potential Drug Target Based on Inflammatory Signature in Primary Lower-Grade Gliomas Frontiers in Oncology lower-grade gliomas inflammatory signature prognostic marker drug targets BRPF1 |
| title | Transcriptional Networks Identify BRPF1 as a Potential Drug Target Based on Inflammatory Signature in Primary Lower-Grade Gliomas |
| title_full | Transcriptional Networks Identify BRPF1 as a Potential Drug Target Based on Inflammatory Signature in Primary Lower-Grade Gliomas |
| title_fullStr | Transcriptional Networks Identify BRPF1 as a Potential Drug Target Based on Inflammatory Signature in Primary Lower-Grade Gliomas |
| title_full_unstemmed | Transcriptional Networks Identify BRPF1 as a Potential Drug Target Based on Inflammatory Signature in Primary Lower-Grade Gliomas |
| title_short | Transcriptional Networks Identify BRPF1 as a Potential Drug Target Based on Inflammatory Signature in Primary Lower-Grade Gliomas |
| title_sort | transcriptional networks identify brpf1 as a potential drug target based on inflammatory signature in primary lower grade gliomas |
| topic | lower-grade gliomas inflammatory signature prognostic marker drug targets BRPF1 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.766656/full |
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