Institute of Pathology, Medizinische Hochschule Hannover, D-30625 Hannover, Germany.
BMC Cancer. 2010 Mar 23;10:109. doi: 10.1186/1471-2407-10-109.
The discovery of small non-coding RNAs and the subsequent analysis of microRNA expression patterns in human cancer specimens have provided completely new insights into cancer biology. Genetic and epigenetic data indicate oncogenic or tumor suppressor function of these pleiotropic regulators. Therefore, many studies analyzed the expression and function of microRNA in human breast cancer, the most frequent malignancy in females. However, nothing is known so far about microRNA expression in male breast cancer, accounting for approximately 1% of all breast cancer cases.
The expression of 319 microRNAs was analyzed in 9 primary human male breast tumors and in epithelial cells from 15 male gynecomastia specimens using fluorescence-labeled bead technology. For identification of differentially expressed microRNAs data were analyzed by cluster analysis and selected statistical methods.Expression levels were validated for the most up- or down-regulated microRNAs in this training cohort using real-time PCR methodology as well as in an independent test cohort comprising 12 cases of human male breast cancer.
Unsupervised cluster analysis separated very well male breast cancer samples and control specimens according to their microRNA expression pattern indicating cancer-specific alterations of microRNA expression in human male breast cancer. miR-21, miR519d, miR-183, miR-197, and miR-493-5p were identified as most prominently up-regulated, miR-145 and miR-497 as most prominently down-regulated in male breast cancer.
Male breast cancer displays several differentially expressed microRNAs. Not all of them are shared with breast cancer biopsies from female patients indicating male breast cancer specific alterations of microRNA expression.
小非编码 RNA 的发现以及随后对人类癌症标本中 microRNA 表达模式的分析，为癌症生物学提供了全新的见解。遗传和表观遗传数据表明，这些多功能调节剂具有致癌或肿瘤抑制功能。因此，许多研究分析了 microRNA 在人类乳腺癌中的表达和功能，乳腺癌是女性最常见的恶性肿瘤。然而，目前对于男性乳腺癌中 microRNA 的表达情况还一无所知，男性乳腺癌约占所有乳腺癌病例的 1%。
使用荧光标记珠技术，对 9 例原发性人男性乳腺癌和 15 例男性乳腺增生症标本中的上皮细胞进行了 319 种 microRNA 的表达分析。为了鉴定差异表达的 microRNA，采用聚类分析和选择的统计学方法对数据进行了分析。在该训练队列中，使用实时 PCR 方法和包含 12 例人男性乳腺癌的独立测试队列，对这些最上调或下调的 microRNA 的表达水平进行了验证。
无监督聚类分析很好地根据 microRNA 表达模式将男性乳腺癌样本与对照标本分开，表明男性乳腺癌中 microRNA 表达存在特异性改变。miR-21、miR-519d、miR-183、miR-197 和 miR-493-5p 被鉴定为上调最显著的 microRNA，miR-145 和 miR-497 被鉴定为下调最显著的 microRNA。
男性乳腺癌存在几种差异表达的 microRNA。并非所有 microRNA 都与女性患者的乳腺癌活检共享，这表明男性乳腺癌的 microRNA 表达存在特异性改变。
