Wang Bin, Li Jindong, Sun Mei, Sun Lihua, Zhang Xingyi
Department of Thoracic Surgery, Second Hospital of Jilin University, Chang Chun, Jilin, 130000, China.
IUBMB Life. 2014 May;66(5):371-7. doi: 10.1002/iub.1273. Epub 2014 May 20.
Breast carcinoma is the most common malignant tumor in females, and lymph node (LN) status is one of the most important prognostic factors in patients with breast cancer. MiRNAs have been shown to have important role in oncogenesis, invasion, and metastasis via epigenetic post-transcriptional gene regulation. However, lymphatic metastasis-related miRNAs of breast cancer has not been well documented. The aim of this study was to identify and evaluate miRNAs related to breast cancer LN metastasis and to explore the clinical significance of the differentially expressed miRNAs in patients with breast cancer. The expression of miRNAs in patients with primary breast cancer with LN metastasis and that without LN metastases was compared by miRNA microarray. We further validated the miRNAs (miR-185-5p, miR-339-5p, miR-542-5p, and miR-3923) between LN (n = 31) and nonlymph node (NLN; n = 42) group using real-time reverse transcriptase polymerase chain reaction. Furthermore, the relationship between miRNA expression and clinical pathological features was analyzed. The miRNA microarray initially identified that eight miRNAs (miR-206, miR-3923, miR-181a, miR-92a, miR-421, miR-339-5p, miR-3196, and miR-29b) were downregulated in LN metastasis group, whereas five miRNAs (miR-542-5p, miR-200a, miR-564, miR-451, miR-30c, miR-200b, miR-191-3p, miR-142-5p, and miR-185-5p) were upregulated in LN group when compared with those in NLN group. In the validation cohort, the expression levels of miR-185-5p and miR-542-5p were significantly expressed higher in LN group (P = 0.002 and P = 0.001, respectively), and the expression levels of miR-339-5p and miR-3923 were significantly expressed lower in LN group (P = 0.001 and P = 0.001, respectively). Our results indicate the potential role of miR-185-5p, miR-542-5p, miR-339-5p, and miR-3923 in predicting metastasis to the LN and prognosis in breast cancers.
乳腺癌是女性最常见的恶性肿瘤,淋巴结(LN)状态是乳腺癌患者最重要的预后因素之一。MicroRNA(miRNA)已被证明通过表观遗传转录后基因调控在肿瘤发生、侵袭和转移中发挥重要作用。然而,乳腺癌淋巴管转移相关的miRNA尚未有充分的文献记载。本研究的目的是鉴定和评估与乳腺癌LN转移相关的miRNA,并探讨差异表达的miRNA在乳腺癌患者中的临床意义。通过miRNA芯片比较原发性乳腺癌伴LN转移患者和无LN转移患者中miRNA的表达。我们使用实时逆转录聚合酶链反应进一步验证了LN组(n = 31)和非淋巴结(NLN;n = 42)组之间的miRNA(miR-185-5p、miR-339-5p、miR-542-5p和miR-3923)。此外,分析了miRNA表达与临床病理特征之间的关系。miRNA芯片最初鉴定出8种miRNA(miR-206、miR-3923、miR-181a、miR-92a、miR-421、miR-339-5p、miR-3196和miR-29b)在LN转移组中表达下调,而5种miRNA(miR-542-5p、miR-200a、miR-564、miR-451、miR-30c、miR-200b、miR-191-3p、miR-142-5p和miR-185-5p)在LN组中相对于NLN组表达上调。在验证队列中,miR-185-5p和miR-542-5p的表达水平在LN组中显著更高(分别为P = 0.002和P = 0.001),而miR-339-5p和miR-3923的表达水平在LN组中显著更低(分别为P = 0.001和P = 0.001)。我们的结果表明miR-185-5p、miR-542-5p、miR-339-5p和miR-3923在预测乳腺癌LN转移和预后方面的潜在作用。