Division of Cancer and Stem Cells, School of Medicine, University of Nottingham and Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, NG5 1PB, UK.
CRUK Cambridge Research Institute, Cambridge, UK.
Br J Cancer. 2018 Apr;118(8):1142-1151. doi: 10.1038/s41416-018-0041-x. Epub 2018 Mar 28.
Mediator complex (MED) proteins have a key role in transcriptional regulation, some interacting with the oestrogen receptor (ER). Interrogation of the METABRIC cohort suggested that MED7 may regulate lymphovascular invasion (LVI). Thus MED7 expression was assessed in large breast cancer (BC) cohorts to determine clinicopathological significance.
MED7 gene expression was investigated in the METABRIC cohort (n = 1980) and externally validated using bc-GenExMiner v4.0. Immunohistochemical expression was assessed in the Nottingham primary BC series (n = 1280). Associations with clinicopathological variables and patient outcome were evaluated.
High MED7 mRNA and protein expression was associated with good prognostic factors: low grade, smaller tumour size, good NPI, positive hormone receptor status (p < 0.001), and negative LVI (p = 0.04) status. Higher MED7 protein expression was associated with improved BC-specific survival within the whole cohort and ER+/luminal subgroup. Pooled MED7 gene expression data in the external validation cohort confirmed association with better survival, corroborating with the protein expression. On multivariate analysis, MED7 protein was independently predictive of longer BC-specific survival in the whole cohort and Luminal A subtype (p < 0.001).
MED7 is an important prognostic marker in BC, particularly in ER+luminal subtypes, associated with improved survival and warrants future functional analysis.
介体复合物（MED）蛋白在转录调控中具有关键作用，其中一些与雌激素受体（ER）相互作用。对 METABRIC 队列的研究表明，MED7 可能调节淋巴血管侵犯（LVI）。因此，评估了大量乳腺癌（BC）队列中 MED7 的表达，以确定其临床病理意义。
在 METABRIC 队列（n=1980）中研究了 MED7 基因表达，并使用 bc-GenExMiner v4.0 进行了外部验证。在诺丁汉原发性 BC 系列（n=1280）中评估了免疫组织化学表达。评估了与临床病理变量和患者预后的相关性。
高 MED7 mRNA 和蛋白表达与良好的预后因素相关：低级别、肿瘤体积较小、良好的 NPI、激素受体状态阳性（p<0.001）和 LVI 状态阴性（p=0.04）。在整个队列和 ER+/luminal 亚组中，较高的 MED7 蛋白表达与改善的 BC 特异性生存相关。在外部验证队列中的合并 MED7 基因表达数据证实了与更好的生存相关，与蛋白表达一致。多变量分析表明，在整个队列和 Luminal A 亚型中，MED7 蛋白是 BC 特异性生存的独立预测因子（p<0.001）。
MED7 是 BC 的一个重要预后标志物，特别是在 ER+luminal 亚型中，与改善的生存相关，值得进一步进行功能分析。
