Genomic instability-associated two-miRNA signature as a novel prognostic biomarker in breast cancer

Abstract

Background: Breast cancer (BC) is the most common cancer among women worldwide and a leading cause of cancer-associated deaths among women. However, there is a lack of accurate prognostic biomarkers for BC. In the present study, we aimed to identify a genomic instability (GI)-associated microRNA signature as a novel potential prognostic biomarker in BC. Methods: We performed an integrative analysis to investigate the relationship between GI and BC and identify GI-associated microRNAs (miRNAs). Subsequently, we conducted a discovery and validation study using multicenter cohorts. The GI-associated miRNA signature was developed in the discovery cohort and independently validated in internal and external cohorts. Results: GI-associated miRNAs expression in BC showed heterogeneity and was significantly correlated with BC prognosis. We identified a GI-associated two-miRNA signature (miR-105-5p and miR-767-5p), termed GI2miR, that stratified BC patients into high-risk and low-risk groups with significantly different clinical outcomes (log-rank p = 0.027) in The Cancer Genome Atlas (TCGA) discovery cohort (n = 763). The prognostic value of GI2miR was further validated in internal TCGA validation cohort (n = 253) (log-rank p = 0.035) and independent GSE22216 cohort (n = 210) (log-rank p = 0.036). The GI2miR demonstrated independent prognostic value in multivariate Cox proportional hazard regression analyses and stratification analysis. Conclusions: We have developed a novel prognostic signature based on GI-associated two miRNAs for BC, which may lay the foundation for BC to improve prognosis prediction.