Association of miR-548c-5p, miR-7-5p, miR-210-3p, miR-128-3p with recurrence in systemically untreated breast cancer

// Ines Block 1 , Mark Burton 1, 2 , Kristina P. Sorensen 1 , Lars Andersen 1, 2 , Martin J. Larsen 1, 2 , Martin Bak 3 , Soren Cold 4 , Mads Thomassen 1, 2 , Qihua Tan 2, 5 and Torben A. Kruse 1, 2 1 Department of Clinical Genetics, Odense University Hospital, Odense, Denmark 2 Human Genetics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark 3 Department of Pathology, Odense University Hospital, Odense, Denmark 4 Department of Oncology, Odense University Hospital, Odense, Denmark 5 Epidemiology, Department of Public Health, University of Southern Denmark, Odense, Denmark Correspondence to: Ines Block, email: Ines.Block@rsyd.dk Keywords: low-risk breast cancer; microRNA; prognosis; lymph node negative; estrogen receptor positive Received: September 24, 2017      Accepted: January 02, 2018      Published: January 09, 2018 ABSTRACT Current prognostic markers allocate the majority of lymph node (LN) negative and estrogen receptor (ER) positive breast cancer patients into the high-risk group. Accordingly, most patients receive systemic treatments although approximately 40% of these patients may have been cured by surgery and radiotherapy alone. Two studies identified seven prognostic microRNAs in systemically untreated, LN negative and ER positive breast cancer patients which may allow more precise patient classification. However, six of the seven microRNAs were analyzed in both studies but only found to be prognostic in one study. To validate their prognostic potential, we analyzed microRNA expression in an independent cohort ( n = 110) using a pair-matched study design minimizing dependence of classical markers. The expression of hsa-miR-548c-5p was significantly associated with abridged disease-free survival (hazard ratio [HR]:1.96, p = 0.027). Contradicting published results, high hsa-miR-516-3p expression was associated with favorable outcome (HR:0.29, p = 0.0068). The association is probably time-dependent indicating later relapse. Additionally, re-analysis of previously published expression data of two matching cohorts ( n = 100, n = 255) supports an association of hsa-miR-128-3p with shortened disease-free survival (HR:2.48, p = 0.0033) and an upregulation of miR-7-5p ( p = 0.0038; p = 0.039) and miR-210-3p ( p = 0.031) in primary tumors of patients who experienced metastases. Further analysis may verify the prognostic potential of these microRNAs.