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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Autores principales:	Mingyang Xia, Huiyao Chen, Tong Chen, Ping Xue, Xinran Dong, Yifeng Lin, Duan Ma, Wenhao Zhou, Wei Shi, Hao Li
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	lower-grade gliomas inflammatory signature prognostic marker drug targets BRPF1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/0a4de17a68684562901dd2bb55154a33
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spelling	oai:doaj.org-article:0a4de17a68684562901dd2bb55154a332021-12-02T05:46:52ZTranscriptional Networks Identify BRPF1 as a Potential Drug Target Based on Inflammatory Signature in Primary Lower-Grade Gliomas2234-943X10.3389/fonc.2021.766656https://doaj.org/article/0a4de17a68684562901dd2bb55154a332021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.766656/fullhttps://doaj.org/toc/2234-943XGliomas 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.Mingyang XiaHuiyao ChenTong ChenPing XueXinran DongYifeng LinDuan MaWenhao ZhouWenhao ZhouWenhao ZhouWei ShiHao LiFrontiers Media S.A.articlelower-grade gliomasinflammatory signatureprognostic markerdrug targetsBRPF1Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lower-grade gliomas inflammatory signature prognostic marker drug targets BRPF1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	lower-grade gliomas inflammatory signature prognostic marker drug targets BRPF1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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
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.
format	article
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
title	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_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_sort	transcriptional networks identify brpf1 as a potential drug target based on inflammatory signature in primary lower-grade gliomas
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0a4de17a68684562901dd2bb55154a33
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_version_	1718400214024323072

Transcriptional Networks Identify BRPF1 as a Potential Drug Target Based on Inflammatory Signature in Primary Lower-Grade Gliomas

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