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

Mingyang Xia; Huiyao Chen; Tong Chen; Ping Xue; Xinran Dong; Yifeng Lin; Duan Ma; Wenhao Zhou; Wei Shi; Hao Li

doi:10.3389/fonc.2021.766656

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

Front Oncol. 2021 Dec 2:11:766656. doi: 10.3389/fonc.2021.766656. eCollection 2021.

Authors

Mingyang Xia¹, Huiyao Chen², Tong Chen¹, Ping Xue³, Xinran Dong⁴, Yifeng Lin¹, Duan Ma⁵, Wenhao Zhou^{2

4

6}, Wei Shi³, Hao Li³

Affiliations

¹ Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai, China.
² Center for Molecular Medicine, Children's Hospital of Fudan University, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
³ Department of Neurosurgery, Children's Hospital of Fudan University, Shanghai, China.
⁴ Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China.
⁵ Key Laboratory of Neonatal Diseases, Division of Neonatology, Children's Hospital of Fudan University, Ministry of Health, Shanghai, China.
⁶ Key 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, China.

Abstract

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.

Keywords: BRPF1; drug targets; inflammatory signature; lower-grade gliomas; prognostic marker.