Department of Pathology, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam, Gyeonggi, 13620, Republic of Korea.
Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Breast Cancer. 2022 Sep;29(5):814-824. doi: 10.1007/s12282-022-01359-9. Epub 2022 Apr 22.
MicroRNAs (miRNAs) control diverse biologic processes during tumor progression. This study was conducted to identify miRNAs that are implicated in progression of in situ to invasive breast cancer (IBC) and to evaluate their association with clinicopathological features of ductal carcinoma in situ (DCIS).
We performed miRNA microarray analyses to find differentially expressed miRNAs between DCIS and IBC in a test set, and validated expression levels of selected miRNAs using a different set of tumors. Finally, we evaluated the relationship between clinicopathological features and the expression of selected miRNAs in DCIS samples.
We found that miR-145-5p, miR-205-5p and miR-451a are significantly down-regulated in IBC compared to DCIS in the whole group, and in the estrogen receptor (ER)-positive and ER-negative subgroups. In a validation set, miR-145, miR-205, and miR-451 also showed lower expression levels in IBC than in DCIS, irrespective of ER status. Moreover, their expression levels were significantly lower in the invasive component compared to the in situ component within same tumors. MiR-145, miR-205 and miR-451 commonly showed lower expression levels in DCIS with positive HER2 status and high Ki-67 proliferation index. Especially, miR-145 and miR-205 showed lower expression levels in DCIS with microinvasion, compared to pure DCIS. In addition, lower miR-205 expression level was associated with high nuclear grade, comedo type necrosis, and hormone receptor negativity.
Our study showed that miR-145, miR-205 and miR-451 expression decreased in IBC compared to DCIS, and their expression levels were low in DCIS with high-risk features for progression, implying their contributions in the progression of DCIS to invasive carcinoma as tumor suppressors.
微小 RNA（miRNA）在肿瘤进展过程中控制着多种生物学过程。本研究旨在鉴定与原位乳腺癌（IBC）进展相关的 miRNA，并评估其与导管原位癌（DCIS）的临床病理特征的关系。
我们进行了 miRNA 微阵列分析，以在测试集中找到 DCIS 和 IBC 之间差异表达的 miRNA，并使用不同的肿瘤集验证选定 miRNA 的表达水平。最后，我们评估了 DCIS 样本中选定 miRNA 的表达与临床病理特征之间的关系。
我们发现，miR-145-5p、miR-205-5p 和 miR-451a 在整个组、雌激素受体（ER）阳性和 ER 阴性亚组中，与 DCIS 相比，在 IBC 中表达明显下调。在验证集中，miR-145、miR-205 和 miR-451 在 IBC 中的表达水平也低于 DCIS，与 ER 状态无关。此外，它们在同一肿瘤的侵袭性成分中的表达水平明显低于原位成分。miR-145、miR-205 和 miR-451 在 HER2 状态阳性和 Ki-67 增殖指数高的 DCIS 中表达水平普遍较低。特别是，与纯 DCIS 相比，miR-145 和 miR-205 在具有微浸润的 DCIS 中表达水平较低。此外，miR-205 表达水平较低与核分级高、粉刺样坏死和激素受体阴性相关。
我们的研究表明，miR-145、miR-205 和 miR-451 在 IBC 中的表达低于 DCIS，并且在具有进展高风险特征的 DCIS 中表达水平较低，这表明它们作为肿瘤抑制因子在 DCIS 向浸润性癌的进展中发挥作用。
