Institute of Molecular Biology and Biophysics, Federal Research Center of Fundamental and Translational Medicine, Timakova Str. 2/12, 630117 Novosibirsk, Russia.
Department of Breast Pathology, Novosibirsk Municipal Publicly Funded Healthcare Institution Municipal Clinical Hospital #1, Zalessky Str. 6, 630047 Novosibirsk, Russia.
Genes (Basel). 2021 Apr 16;12(4):582. doi: 10.3390/genes12040582.
In ~70% of breast cancer (BC) cases, estrogen and progesterone receptors (ER and PR) are overexpressed, which can change during tumor progression. Expression changes of these receptors during cancer initiation and progression can be caused by alterations in microRNA (miR, miRNA) expression. To assess the association of BC progression with aberrant expression of miRNAs that target ER and PR mRNAs, we quantified miR-19b, -222, -22, -378a, and -181a in BC samples ( = 174) by real-time PCR. Underexpression of miR-222 and miR-378a in stage T2-T4 BC was characteristic for HER2-overexpressing tumors. In addition, the expression of miR-181a and miR-378a was higher in these tumors than in tumors with a HER2 IHC score of 0 or 1+. In tumors with a Ki-67 index ≥ 14%, all tested miRNAs were underexpressed in BC with a high Allred PR score (6-8). In ER-and-PR-negative tumors, miR-22, miR-222, miR-181a, and miR-378a underexpression was associated with Ki-67 index > 35% (median value). MiR-19b and miR-22 underexpression could be a marker of lymph node metastasis in ER- and/or PR-positive tumors with HER2 IHC score 0. Thus, the association of miR-19b, miR-22, miR-222, miR-378a, and miR-181a levels with BC characteristics is influenced by the status of tumor ER, PR, HER2, and Ki-67.
在约 70%的乳腺癌 (BC) 病例中，雌激素和孕激素受体 (ER 和 PR) 过表达，这些受体在肿瘤进展过程中可能发生变化。这些受体在癌症起始和进展过程中的表达变化可能是由 microRNA (miR, miRNA) 表达的改变引起的。为了评估 BC 进展与靶向 ER 和 PR mRNA 的 miRNAs 异常表达之间的关联，我们通过实时 PCR 定量检测了 BC 样本 (= 174) 中的 miR-19b、-222、-22、-378a 和 -181a。HER2 过表达肿瘤的 T2-T4 期 BC 中 miR-222 和 miR-378a 的低表达是其特征。此外，这些肿瘤中 miR-181a 和 miR-378a 的表达高于 HER2 IHC 评分 0 或 1+的肿瘤。在 Ki-67 指数≥14%的肿瘤中，高 Allred PR 评分 (6-8) 的 BC 中所有检测到的 miRNAs 均低表达。在 ER 和 PR 阴性肿瘤中，miR-22、miR-222、miR-181a 和 miR-378a 的低表达与 Ki-67 指数 > 35%（中位数）相关。在 ER 和/或 PR 阳性且 HER2 IHC 评分 0 的肿瘤中，miR-19b 和 miR-22 的低表达可能是淋巴结转移的标志物。因此，miR-19b、miR-22、miR-222、miR-378a 和 miR-181a 水平与 BC 特征的关联受肿瘤 ER、PR、HER2 和 Ki-67 状态的影响。
