Centro Regional de Investigaciones Biomedicas, Castilla-La Mancha University (CRIB-UCLM), Calle Almansa, 14, 02008, Albacete, Spain.
Instituto de Biología Molecular y Celular del Cáncer and CIBERONC. CSIC-Universidad de Salamanca, Campus Miguel de Unamuno, 37007, Salamanca, Spain.
Sci Rep. 2019 Apr 5;9(1):5734. doi: 10.1038/s41598-019-41934-3.
A specific family of proteins that participate in epigenetic regulation is the bromodomain (BRD) family of proteins. In this work, we aimed to explore the expression of the BRD family at a transcriptomic level in breast cancer, and its association with patient survival. mRNA level data from normal breast and tumor tissues were extracted from public datasets. Gene set enrichment analysis (GSEA) was performed to identify relevant biological functions. The KM Plotter Online tool was used to evaluate the relationship between the presence of different genes and patient clinical outcome. mRNA level data from HER2+ breast cancer patients sensible and resistant to trastuzumab were also evaluated. The BRD family was an enriched function. In HER2 positive tumors the combined analyses of BRD2, BAZ1A, TRIM33 and ZMYND8 showed a detrimental relapse free survival (RFS). Similarly, the combined analysis of BRD2, BAZ1A, PHIP, TRIM33, KMT2A, ASH1L, PBRM1, correlated with an extremely poor overall survival (OS). The prognosis was confirmed using an independent dataset from TCGA. Finally, no relation between expression of BRD genes and response to trastuzumab was observed in the HER2 population. Upregulation of some BRD genes is associated with detrimental outcome in HER2 positive tumors, regardless trastuzumab treatment.
一组参与表观遗传调控的特定蛋白质家族是溴结构域（BRD）家族的蛋白质。在这项工作中，我们旨在探索 BRD 家族在乳腺癌中的转录组水平表达及其与患者生存的关系。从公共数据集提取正常乳腺组织和肿瘤组织的 mRNA 水平数据。进行基因集富集分析（GSEA）以鉴定相关的生物学功能。使用 KM Plotter Online 工具评估不同基因的存在与患者临床结局之间的关系。还评估了对曲妥珠单抗敏感和耐药的 HER2+乳腺癌患者的 mRNA 水平数据。BRD 家族是一个富集的功能。在 HER2 阳性肿瘤中，BRD2、BAZ1A、TRIM33 和 ZMYND8 的联合分析显示无复发生存（RFS）不良。同样，BRD2、BAZ1A、PHIP、TRIM33、KMT2A、ASH1L、PBRM1 的联合分析与极差的总生存（OS）相关。使用来自 TCGA 的独立数据集证实了该预后。最后，在 HER2 人群中未观察到 BRD 基因表达与曲妥珠单抗反应之间的关系。一些 BRD 基因的上调与 HER2 阳性肿瘤的不良结局相关，无论是否接受曲妥珠单抗治疗。
