Chen Yi-Ru, Ouyang Su-Shan, Chen Yan-Ling, Li Ping, Xu Hui-Wen, Zhu Sen-Lin
Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Department of Anesthesiology, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Aging (Albany NY). 2020 Sep 14;12(17):17541-17567. doi: 10.18632/aging.103768.
Bromodomain (BRD)-containing proteins are a class of epigenetic readers with unique recognition for N-acetyl-lysine in histones and functions of gene transcription and chromatin modification, known to be critical in various cancers. However, little is known about the roles of distinct BRD-containing protein genes in hepatocellular carcinoma (HCC). Most recently, we investigated the transcriptional and survival data of BRD1, BRD2, BRD3, BRD4, BRD7, BRD8, BRD9 in HCC patients through ONCOMINE, UALCAN, Human Protein Atlas, GEPIA, cBioPortal, STRING, TIMER databases. BRD1/2/3/4/7/8/9 were over-expressed in HCC and were significantly associated with clinical cancer stages and pathological tumor grades. High mRNA expressions of BRD4/8/9 were promising candidate biomarkers in HCC patients. The rate of sequence alternations in BRD1/2/3/4/7/8/9 was relatively high (52%) in HCC patients, and the genetic alternations were correlated with shorter overall survival and disease-free survival in HCC patients. Additionally, the mRNA expression levels of individual BRD genes were significantly positively associated with the immune infiltrating levels of B cells, CD8 T cells, CD4 T cells, macrophages, neutrophils, and dendritic cells. And the associations between BRD1/2/3/4/7/8/9 and diverse immune marker sets showed a significance. Overall, these results indicated that BRD4/8/9 could be potential prognostic markers and druggable epigenetic targets in HCC patients.
含溴结构域（BRD）的蛋白质是一类表观遗传识别蛋白，对组蛋白中的N - 乙酰赖氨酸具有独特的识别能力，并具有基因转录和染色质修饰功能，已知在多种癌症中起关键作用。然而，关于不同的含BRD蛋白基因在肝细胞癌（HCC）中的作用知之甚少。最近，我们通过ONCOMINE、UALCAN、人类蛋白质图谱、GEPIA、cBioPortal、STRING、TIMER数据库研究了HCC患者中BRD1、BRD2、BRD3、BRD4、BRD7、BRD8、BRD9的转录和生存数据。BRD1/2/3/4/7/8/9在HCC中过表达，且与临床癌症分期和病理肿瘤分级显著相关。BRD4/8/9的高mRNA表达是HCC患者有前景的候选生物标志物。HCC患者中BRD1/2/3/4/7/8/9的序列改变率相对较高（52%），且基因改变与HCC患者较短的总生存期和无病生存期相关。此外，单个BRD基因的mRNA表达水平与B细胞、CD8 T细胞、CD4 T细胞、巨噬细胞、中性粒细胞和树突状细胞的免疫浸润水平显著正相关。并且BRD1/2/3/4/7/8/9与多种免疫标志物集之间的关联具有显著性。总体而言，这些结果表明BRD4/8/9可能是HCC患者潜在的预后标志物和可成药的表观遗传靶点。
