Department of Pathology, Tianjin Medical University Cancer Hospital, China; Department of Breast Surgery, Harbin Medical University Cancer Hospital, China; Department of Plastic and Cosmetic Surgery, The First Affiliated Hospital of Harbin Medical University, China.
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, China.
Pathol Res Pract. 2021 Jan;217:153310. doi: 10.1016/j.prp.2020.153310. Epub 2020 Dec 4.
The androgen receptor (AR, NR3C4) is believed to participate in the development of breast cancer, but its molecular mechanism and role in prognosis is still controversial and opaque. This study aimed to explore the expression, associations with clinicopathologic features and underlying molecular mechanisms of AR in breast cancer. The present study investigated invasive breast carcinoma through comprehensive bioinformatics. The expression and mutation rate of AR in breast cancer was obtained from the TCGA database. Training survival prediction analysis was applied to the data extracted from the KM plotter database. The prediction of the survival cohort was validated using the bcGenExMiner database in breast cancer molecular subgroups. Represented immunohistochemical images of AR and its related expression with the molecular subtype status were generated. The underlying molecular mechanism for AR in breast cancer was analyzed with the GEO dataset and Gene Ontology. A protein-to-protein interaction network and core pathways were constructed to show the protein functions with AR. Our results show that AR expression was significantly higher in cancerous tissue than in normal breast tissue and differentially expressed in the clinical stages. AR would also generally be considered as a favorable prognostic biomarker when including the major molecular subtypes of breast cancer. AR IHC staining could be easily used in clinical applications. The major molecular functions for AR were regulating the cell cycle checkpoints and chromatin remodeling. Our investigation showed that AR expression level could be used as a favorable and independent prognostic prediction factor for the disease-free survival time in breast cancer, especially for the ER-positive subgroup. However, AR was not a sensitive prognostic biomarker for the prediction of overall survival time or for the PR and TBC subgroups. In terms of the underlying molecular mechanism, AR may mainly participate in the cell cycle checkpoints related to the G1/S transition of the mitotic cell cycle to control the subdivision of the epithelial terminal unit and chromatin remodeling in breast cancer.
雄激素受体（AR，NR3C4）被认为参与乳腺癌的发生发展，但它在乳腺癌中的分子机制和预后作用仍存在争议和不明确。本研究旨在探讨 AR 在乳腺癌中的表达、与临床病理特征的相关性及其潜在的分子机制。本研究通过综合生物信息学方法研究浸润性乳腺癌。从 TCGA 数据库中获取 AR 在乳腺癌中的表达和突变率。对从 KM plotter 数据库中提取的数据进行训练生存预测分析。使用 bcGenExMiner 数据库对乳腺癌分子亚群中的生存队列进行预测验证。生成 AR 及其与分子亚型状态相关表达的代表性免疫组化图像。利用 GEO 数据集和基因本体论分析 AR 在乳腺癌中的潜在分子机制。构建蛋白质-蛋白质相互作用网络和核心途径，以显示与 AR 相关的蛋白质功能。结果表明，AR 表达在癌组织中明显高于正常乳腺组织，且在临床分期中差异表达。当包括乳腺癌的主要分子亚型时，AR 通常被认为是一种有利的预后生物标志物。AR IHC 染色可在临床应用中轻松使用。AR 的主要分子功能是调节细胞周期检查点和染色质重塑。研究表明，AR 表达水平可作为乳腺癌无病生存时间的有利且独立的预后预测因素，特别是在 ER 阳性亚组中。然而，AR 并不是预测总生存时间或 PR 和 TBC 亚组的敏感预后生物标志物。在潜在的分子机制方面，AR 可能主要参与与有丝分裂细胞周期的 G1/S 转换相关的细胞周期检查点，以控制乳腺癌中上皮终末单位的细分和染色质重塑。
