In silico identification of ADRA2A-associated miRNA expression as biomarkers for disease-free survival in breast cancer subtypes

Abstract

Breast cancer (BC) is the most frequently diagnosed and leading cause of cancer death among women worldwide. We previously described that the expression of the α2A adrenoceptor (ADRA2A) is an independent good prognostic factor in luminal tumors. We interrogated in the public TCGA database the expression of miRNAs able to bind to the ADRA2A 3´UTR and we selected for further studies those which correlated with ADRA2A expression. The cutoff points for disease-free survival (DFS) were selected using the Evaluate Cutpoint. Survival analysis was performed by Kaplan?Meier and log‐rank (Mantel?Cox).A high expression of ADRA2A was significantly associated with better DFS as previously shown. hsa-miR 23a-3p, 30a-5p, 30e-5p, 33a-5p, 33b-5p, 135b-5p and 138-5p correlated with ADRA2A expression. When they were evaluated for prognosis ability, a high expression of 135b-5p proved significantly associated with DFS in the whole cohort and in basal-like tumors in particular. The opposite was found for 23a-3p. A high expression of 30e-5p was associated with better DFS in luminal A, while 33a-5p was associated with longer DFS in luminal tumors in general, and luminal B in particular. In fact, high 30e-5p and 33a-5p expression exhibited 100% DFS in these subtypes. 30e-5p was overexpressed in luminal A (as has already been described) and 23a-3p, 30e-5p, 33a-5p, 135b-5p and 138-5p in basal-like tumors. These miRNAs and ADRA2A might be selectively used as prognostic biomarkers in the different BC subtypes.