Kalinina Tatiana S, Kononchuk Vladislav V, Yakovleva Alisa K, Alekseenok Efim Y, Sidorov Sergey V, Gulyaeva Lyudmila F
Institute of Molecular Biology and Biophysics-Subdivision of Federal Research Center of Fundamental and Translational Medicine, Timakova Str. 2/12, 630117 Novosibirsk, Russia.
Novosibirsk State University, Pirogova Str. 1, 630090 Novosibirsk, Russia.
Int J Breast Cancer. 2020 Apr 23;2020:3259393. doi: 10.1155/2020/3259393. eCollection 2020.
Breast cancer is the most commonly diagnosed cancer among women. Difficulties in treating breast cancer are associated with the occurrence of metastases at early stages of disease, leading to its further progression. Recent studies have shown that changes in androgen receptor (AR) and microRNAs' expressions are associated with mammary gland carcinogenesis, in particular, with the formation of metastases. Thus, to identify novel metastatic markers, we evaluated the expression levels of AR; miR-185 and miR-205, both of which have been confirmed to target AR; and miR-21, transcription of which is regulated by AR, in breast cancer samples ( = 89). Here, we show that the molecular subtypes of breast cancer differ in the expression profiles of AR and AR-associated microRNAs. In addition, the expression of AR and these microRNAs may depend on the expression of PR, ER, and HER2 receptors. Our results show that the possibility of using AR and microRNAs as markers depends on the tumor subtype: a decrease in AR expression may be the marker for the presence of lymph node metastases in patients with HER2-positive subtypes of breast cancer, and disturbance of miR-205, miR-185, and miR-21 expressions may be the marker in patients with a luminal B HER2-positive subtype. Cases with metastases in this type of breast cancer are characterized by a higher level of miR-205 and a lower level of miR-185 and miR-21 in tumor tissues compared to nonmetastatic cases. A decrease in the miR-185 level is also associated with lymph node metastasis in luminal B HER2-negative breast cancer. Thus, the expression levels of AR, miR-185, miR-205, and miR-21 can serve as markers to predict cancer spread to the lymph node in luminal B- and HER2-positive subtypes of breast cancer.
乳腺癌是女性中最常被诊断出的癌症。乳腺癌治疗的困难与疾病早期转移的发生有关，导致其进一步发展。最近的研究表明，雄激素受体（AR）和微小RNA表达的变化与乳腺癌发生相关，特别是与转移的形成有关。因此，为了鉴定新的转移标志物，我们评估了AR；miR-185和miR-205（二者均已证实靶向AR）；以及miR-21（其转录受AR调控）在89例乳腺癌样本中的表达水平。在此，我们表明乳腺癌的分子亚型在AR及AR相关微小RNA的表达谱上存在差异。此外，AR和这些微小RNA的表达可能取决于PR、ER和HER2受体的表达。我们的结果表明，将AR和微小RNA用作标志物的可能性取决于肿瘤亚型：AR表达降低可能是HER2阳性亚型乳腺癌患者存在淋巴结转移的标志物，而miR-205、miR-185和miR-21表达紊乱可能是管腔B型HER2阳性亚型患者的标志物。与无转移病例相比，这种类型乳腺癌的转移病例在肿瘤组织中miR-205水平较高，而miR-185和miR-21水平较低。miR-185水平降低也与管腔B型HER2阴性乳腺癌的淋巴结转移有关。因此，AR、miR-185、miR-205和miR-21的表达水平可作为预测管腔B型和HER2阳性亚型乳腺癌向淋巴结转移的标志物。
