miR-205-5p Downregulation and <i>ZEB1</i> Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer

oleh: Lenka Kalinkova, Nataliia Nikolaieva, Bozena Smolkova, Sona Ciernikova, Karol Kajo, Vladimir Bella, Viera Horvathova Kajabova, Helena Kosnacova, Gabriel Minarik, Ivana Fridrichova

Format: Article
Diterbitkan: MDPI AG 2021-12-01

Deskripsi

Background: Dissemination of breast cancer (BC) cells through the hematogenous or lymphogenous vessels leads to metastatic disease in one-third of BC patients. Therefore, we investigated the new prognostic features for invasion and metastasis. Methods: We evaluated the expression of miRNAs and epithelial-to-mesenchymal transition (EMT) genes in relation to <i>CDH1</i>/E-cadherin changes in samples from 31 patients with invasive ductal BC including tumor centrum (TU-C), tumor invasive front (TU-IF), lymph node metastasis (LNM), and CD45-depleted blood (CD45-DB). Expression of miRNA and mRNA was quantified by RT-PCR arrays and associations with clinico-pathological characteristics were statistically evaluated by univariate and multivariate analysis. Results: We did not verify <i>CDH1</i> regulating associations previously described in cell lines. However, we did detect extremely high <i>ZEB1</i> expression in LNMs from patients with distant metastasis, but without regulation by miR-205-5p. Considering the ZEB1 functions, this overexpression indicates enhancement of metastatic potential of lymphogenously disseminated BC cells. In CD45-DB samples, downregulated miR-205-5p was found in those expressing epithelial and/or mesenchymal markers (CTC+) that could contribute to insusceptibility and survival of hematogenously disseminated BC cells mediated by increased expression of several targets including <i>ZEB1</i>. Conclusions: miR-205-5p and potentially <i>ZEB1</i> gene are promising candidates for markers of metastatic potential in ductal BC.