Department of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, Slovakia.
Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, Slovakia.
Int J Mol Sci. 2021 Dec 22;23(1):103. doi: 10.3390/ijms23010103.
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.
We evaluated the expression of miRNAs and epithelial-to-mesenchymal transition (EMT) genes in relation to /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.
We did not verify regulating associations previously described in cell lines. However, we did detect extremely high 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 .
miR-205-5p and potentially gene are promising candidates for markers of metastatic potential in ductal BC.
乳腺癌(BC)细胞通过血液或淋巴系统传播,导致三分之一的 BC 患者发生转移性疾病。因此,我们研究了新的侵袭和转移的预后特征。
我们评估了 miRNA 和上皮间质转化(EMT)基因的表达与 E-钙黏蛋白变化的关系,这些变化来自 31 例浸润性导管 BC 患者的样本,包括肿瘤中心(TU-C)、肿瘤侵袭前沿(TU-IF)、淋巴结转移(LNM)和 CD45 耗尽的血液(CD45-DB)。通过 RT-PCR 阵列定量检测 miRNA 和 mRNA 的表达,并通过单变量和多变量分析统计评估与临床病理特征的关联。
我们没有验证先前在细胞系中描述的调节关联。然而,我们确实在有远处转移但不受 miR-205-5p 调节的患者的 LNM 中检测到极高的表达。考虑到 ZEB1 的功能,这种过表达表明淋巴源性播散的 BC 细胞的转移潜力增强。在 CD45-DB 样本中,那些表达上皮和/或间充质标志物(CTC+)的样本中发现下调的 miR-205-5p,这可能有助于血液播散的 BC 细胞的不敏感性和存活,这是由包括在内的多个靶标的表达增加介导的。
miR-205-5p 和潜在的基因是导管 BC 转移潜力的有前途的候选标志物。