含溴结构域(BRD)的蛋白质是一类表观遗传读写器,对组蛋白中的N-乙酰赖氨酸具有独特的识别,并具有基因转录和染色质修饰的功能。已知在各种癌症中至关重要。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,我们调查了BRD1,BRD2,BRD3,BRD4,BRD7,BRD8,BRD9在肝癌患者中的转录和生存数据,UALCAN,人类蛋白质图谱,GEPIA,cBioPortal,STRING,TIMER数据库。BRD1/2/3/4/7/8/9在HCC中过度表达,并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患者的有希望的候选生物标志物。在HCC患者中BRD1/2/3/4/7/8/9的序列交替率相对较高(52%),遗传改变与HCC患者的总生存期和无病生存期较短相关。此外,单个BRD基因的mRNA表达水平与B细胞的免疫浸润水平呈显著正相关,CD8+T细胞,CD4+T细胞,巨噬细胞,中性粒细胞,和树突状细胞。BRD1/2/3/4/7/8/9与不同免疫标记集之间的关联显示出显著性。总的来说,这些结果表明,BRD4/8/9可能是HCC患者的潜在预后标志物和药物表观遗传靶标.
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.