Association between microRNAs expression in primary breast cancer and presence of circulating tumor cells (CTC) in peripheral blood.

e23022 Background: CTCs play major role in tumor dissemination and progression and represent one of the key component of metastatic cascade. MicroRNAs (miRs) are involved in regulation in several biological processes in cancer including invasion, epithelial-mesenchymal transition (EMT) and disease progression. The aim of this study was to identify miRs in primary tumor associated with presence of CTCs in peripheral blood (PB) in non-metastatic breast cancer patients. Methods: This translational study included 79 patients with primary breast cancer for whom fresh frozen tumor tissue and status of CTCs in peripheral blood were available. CTCs were detected before surgery by qRT-PCR assay for expression of epithelial (CK19) or epithelial-mesenchymal transition (EMT) genes (TWIST1, SNAIL1, SLUG, ZEB1). Total RNA was extracted from fresh frozen primary tumor and the expression profiles were obtained using Human microRNA Microarray v21.0 (Agilent Technologies). Results: We analyzed 48 (60.8%) tumor samples from patients with presence of CTCs in PB and 31 (39.2%) tumors with non-detectable CTCs. From CTCs positive patients, in 20 (41.7%) of them epithelial CTCs (EP_CTC) were detected while in 28 (38.3%) CTCs with EMT (CTC_EMT) phenotype were present. We identified 178 miRs that were expressed at significantly different levels (FDR < 0.05) in tumors with presence of any type of CTCs in PB compared to tumors with non-detectable CTCs. We also identified 174 and 137 miRs (33 overlapping) that were expressed at significantly different levels in tumors with EP_CTCs and CTC_EMT, respectively, compared to tumors with non-detectable CTCs. Overlapping miRs with highest different levels in expression (FDR < 0.01) were miR-3137, miR-3138, miR-3168, miR-605-5p, miR-6165 and miR-6790-5p. Conclusions: We identified for the first time miRs expressed in primary tumor associated with CTCs in peripheral blood in breast cancer patients. Moreover, we identified miRs specifically associated with various subpopulations of CTCs. We suppose, that these miRs could be involved in tumor dissemination and might lead to identification of new therapeutic targets. Study was supported by APVV-14-0327.