miRNA expression in breast cancer varies with lymph node metastasis and other clinicopathologic features

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.