Clinical significance of long non-coding RNA ZEB2-AS1 and EMT-related markers in ductal and lobular breast cancer

Background: Breast cancer is considered the most prevalent type of cancer in women and accounts for a high rate of death. A body of research has demonstrated that lncRNAs have a regulatory function in human diseases, especially cancers. ZEB2-AS1 is known as an oncogenic lncRNA in various types of cancers, and its deregulation may contribute to cancer development and progression. Therefore, we aimed to reveal the association of ZEB2-AS1 expression with epithelial-mesenchymal transition (EMT) markers, as a hallmark of cancer progression, in a clinical setting.

Methods: A recent study suggested that ZEB2-AS1 is significantly involved in EMT. Here we intended to explore the roles of lncRNA ZEB2-AS1 in breast cancer (BC) using bioinformatics tools and laboratory settings. We first evaluated the expression of ZEB2-AS1 mRNA in tumor and healthy control tissues by lnCAR database. Furthermore, ZEB2-AS1 expression level, ZEB2, E-cadherin, and vimentin was measured via qRT-PCR in 30 paired ductal and lobular carcinoma tissues from breast cancer patients and the normal adjacent ones. The correlation between the lncRNA ZEB2-AS1 expression and clinicopathological characteristics of the breast cancer patients was evaluated.

Results: ZEB2-AS1 showed an upregulation in breast cancer tissues (p = .04) compared to normal adjacent samples. In addition, its level was higher in breast cancer patients with advanced Stages (III & IV) (n = 18) compared to early Stages (I & II) (n = 12) (p = .04). Moreover, ZEB2 (p = .01) and vimentin (p = .02) expression were upregulated in the BC sample, but the expression level of E-cadherin (p = .02) was downregulated when compared with the adjacent normal tissues. By comparison of the expression of EMT-markers between different stages of breast cancer, overexpression of ZEB2 (p = .04) and vimentin (p = .04) and down expression of E-cadherin (p = .03) was observed in advance stages.

Conclusions: Collectively, our findings suggest that ZEB2-AS1 expression is significantly upregulated in tumor tissues, especially in advanced stages and ZEB2-AS1 is associated with the aggressiveness of tumors by functioning as putative oncogenic lncRNA. In addition, a combination of ZEB2-AS1 and these EMT markers in breast cancer potentiates these genes as biomarkers for tumor progression.