Down-regulation of traditional oncomiRs in plasma of breast cancer patients

Abstract

// Dana Jurkovicova 1, 2 , Bozena Smolkova 2 , Monika Magyerkova 1 , Zuzana Sestakova 2 , Viera Horvathova Kajabova 2 , Ludovit Kulcsar 1 , Iveta Zmetakova 2 , Lenka Kalinkova 2 , Tomas Krivulcik 2 , Marian Karaba 3 , Juraj Benca 3, 4 , Tatiana Sedlackova 5 , Gabriel Minarik 5 , Zuzana Cierna 6 , Ludovit Danihel 6, 7 , Michal Mego 8 , Miroslav Chovanec 2 and Ivana Fridrichova 2 1 KRD Molecular Technologies Ltd., Bratislava, Slovakia 2 Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia 3 Department of Surgical Oncology, National Cancer Institute, Bratislava, Slovakia 4 Medical Department of St. Elizabeth University, Bratislava, Slovakia 5 Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia 6 Institute of Pathological Anatomy, Faculty of Medicine, Comenius University, University Hospital, Bratislava, Slovakia 7 Pathological-Anatomical Workplace, Health Care Surveillance Authority, Bratislava, Slovakia 8 2 nd Department of Oncology, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia Correspondence to: Ivana Fridrichova, email: ivana.fridrichova@savba.sk Keywords: miR-17/92 cluster, miR-21, miR-27a, miR-155, down-regulation of oncomiRs Received: May 05, 2017      Accepted: July 25, 2017      Published: August 24, 2017 ABSTRACT Deregulated expression of microRNAs has the oncogenic or tumor suppressor function in cancer. Since miRNAs in plasma are highly stable, their quantification could contribute to more precise cancer diagnosis, prognosis and therapy prediction. We have quantified expression of seven oncomiRs, namely miR-17/92 cluster (miR-17, miR-18a, miR-19a and miR-20a), miR-21, miR-27a and miR-155, in plasma of 137 breast cancer (BC) patients. We detected down-regulation of six miRNAs in patients with invasive BC compared to controls; however, only miR-20a and miR-27a down-regulations were statistically significant. Comparing miRNA expression between early and advanced stages of BC, we observed statistically significant decrease of miR-17 and miR-19a. We identified down-regulation of miR-17 and miR-20a in patients with clinical parameters of advanced BC (lymph node metastasis, tumor grade 3, circulating tumor cells, higher Ki-67-related proliferation, hormone receptor negativity and HER2 amplification), when compared to controls. Moreover, decreased level of miR-17 was found from low to high grade. Therefore, miR-17 could represent an indicator of advanced BC. Down-regulated miR-27a expression levels were observed in all clinical categories regardless of tumor progression. Hence, miR-27a could be used as a potential diagnostic marker for BC. Our data indicates that any changes in miRNA expression levels in BC patients in comparison to controls could be highly useful for cancer-associated pathology discrimination. Moreover, dynamics of miRNA expression changes could be used for BC progression monitoring.