Lu Junwan, Qian Changrui, Ji Yongan, Bao Qiyu, Lu Bin
Protein Quality Control and Diseases Laboratory, Key Laboratory of Medical Genetics of Zhejiang Province, Key Laboratory of Laboratory Medicine, Ministry of Education of China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
Wenzhou Central Hospital, Wenzhou, China.
Front Genet. 2021 Jun 2;12:643935. doi: 10.3389/fgene.2021.643935. eCollection 2021.
Bromodomain (BRD) proteins exhibit a variety of activities, such as histone modification, transcription factor recruitment, chromatin remodeling, and mediator or enhancer complex assembly, that affect transcription initiation and elongation. These proteins also participate in epigenetic regulation. Although specific epigenetic regulation plays an important role in the occurrence and development of cancer, the characteristics of the BRD family in renal clear cell carcinoma (KIRC) have not been determined. In this study, we investigated the expression of BRD family genes in KIRC at the transcriptome level and examined the relationship of the expression of these genes with patient overall survival. mRNA levels of tumor tissues and adjacent tissues were extracted from The Cancer Genome Atlas (TCGA) database. Seven BRD genes (, and ) were searched by using LASSO Cox regression and the model with prognostic risk integration. The patients were divided into two groups: high risk and low risk. The combined analysis of these seven BRD genes showed a significant association with the high-risk groups and lower overall survival (OS). This analysis demonstrated that total survival could be predicted well in the low-risk group according to the time-dependent receiver operating characteristic (ROC) curve. The prognosis was determined to be consistent with that obtained using an independent dataset from TCGA. The relevant biological functions were identified using Gene Set Enrichment Analysis (GSEA). In summary, this study provides an optimized survival prediction model and promising data resources for further research investigating the role of the expression of BRD genes in KIRC.
溴结构域（BRD）蛋白具有多种活性，如组蛋白修饰、转录因子募集、染色质重塑以及中介体或增强子复合物组装等，这些活性会影响转录起始和延伸。这些蛋白还参与表观遗传调控。尽管特定的表观遗传调控在癌症的发生和发展中起着重要作用，但肾透明细胞癌（KIRC）中BRD家族的特征尚未明确。在本研究中，我们在转录组水平上研究了KIRC中BRD家族基因的表达，并检测了这些基因的表达与患者总生存期的关系。从癌症基因组图谱（TCGA）数据库中提取肿瘤组织和邻近组织的mRNA水平。通过使用LASSO Cox回归和具有预后风险整合的模型搜索了7个BRD基因（ 、 和 ）。将患者分为两组：高风险组和低风险组。这7个BRD基因的联合分析显示与高风险组和较低的总生存期（OS）显著相关。根据时间依赖性受试者工作特征（ROC）曲线分析表明，低风险组的总生存期可以得到很好的预测。确定该预后与使用来自TCGA的独立数据集所获得的预后一致。使用基因集富集分析（GSEA）确定相关的生物学功能。总之，本研究为进一步研究BRD基因表达在KIRC中的作用提供了优化的生存预测模型和有前景的数据资源。
