雄激素受体（AR）被认为是激素受体阳性乳腺癌（BC）预后良好的标志物，然而，它在三阴性乳腺癌（TNBC）中的作用是有争议的。这可能归因于固有的分子差异或评分AR阳性的方法。我们通过应用生物信息学流程在公开可用的AR阳性BC细胞系的微阵列数据集上推导了AR调控的基因评分，并计算了六个AR调控的基因的平均表达作为基因评分。根据基因评分将肿瘤分为AR高和低，并研究其与临床参数、周围循环雄激素、生存和上皮-间质转变（EMT）标志物的关联，进一步在体内模型和公共数据集中进行了评估。有53％（133/249）的肿瘤被归类为AR基因评分高，并且与临床参数显著好、无病生存期（86.13vs 72.69个月，log rank p = 0.032）相关，与AR基因评分低肿瘤相比。36％的TNBC（N = 66）AR基因评分高，同时表达EMT标志物更高（p = 0.024），并且在肿瘤内存在较高水平的5α-还原酶，这是一种参与细胞内雄激素代谢的酶。在经受二氢睾酮处理的MDA-MB-453细胞中，SLUG表达增加，E-钙黏蛋白降低，迁移增加，而使用比卡鲁胺可以逆转这些变化。公共数据集中也得到了类似的结果。仅根据AR蛋白水平来解读AR在BC中的作用是困难的。我们的结果支持AR在驱动ER阳性肿瘤的预后良好和TNBC肿瘤中的EMT特征方面的情境依赖性功能。 版权所有 © 2023。由Elsevier Inc.发布。

Androgen receptor (AR) is considered a marker of better prognosis in hormone receptor positive breast cancers (BC), however, its role in triple negative breast cancer (TNBC) is controversial. This may be attributed to intrinsic molecular differences or scoring methods for AR positivity. We derived AR regulated gene score and examined its utility in BC subtypes.AR regulated genes were derived by applying a bioinformatic pipeline on publicly available microarray data sets of AR+ BC cell lines and gene score was calculated as average expression of six AR regulated genes. Tumors were divided into AR high and low based on gene score and associations with clinical parameters, circulating androgens, survival and epithelial to mesenchymal transition (EMT) markers were examined, further evaluated in invitro models and public datasets.53% (133/249) tumors were classified as AR gene score high and were associated with significantly better clinical parameters, disease-free survival (86.13 vs 72.69 months, log rank p = 0.032) when compared to AR low tumors. 36% of TNBC (N = 66) were AR gene score high with higher expression of EMT markers (p = 0.024) and had high intratumoral levels of 5α-reductase, enzyme involved in intracrine androgen metabolism. In MDA-MB-453 treated with dihydrotestosterone, SLUG expression increased, E-cadherin decreased with increase in migration and these changes were reversed with bicalutamide. Similar results were obtained in public datasets.Deciphering the role of AR in BC is difficult based on AR protein levels alone. Our results support the context dependent function of AR in driving better prognosis in ER positive tumors and EMT features in TNBC tumors.Copyright © 2023. Published by Elsevier Inc.