A novel six-microRNA-based model to improve prognosis prediction of breast cancer

Abstract

Current tumor-node-metastasis (TNM) stage is unable to accurately predict the overall survival (OS) in breast cancer (BC) patients. This study aimed to construct a microRNA (miRNA)-based model to improve survival prediction of BC. We confirmed 99 differentially expressed miRNAs (DEMs) in 1044 BC samples compared to 102 adjacent normal breast tissues from The Cancer Genome Atlas (TCGA) database. Prognostic DEMs were used to establish a miRNA-based nomogram via Cox regression model. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses (KEGG) were executed to analyze target genes of miRNAs. A six-miRNA signature was screened to effectively distinguish high-risk patients in the primary and validation cohort (all P<0.001). Furthermore, we established a novel prognostic model incorporating the six-miRNA signature and clinical risk factors to predict 5-year OS of BC. Time-dependent receiver operating characteristic analysis suggested that the predictive accuracy of the six-miRNA-based nomogram was distinctly higher than that of TNM stage (0.758 vs 0.650, P<0.001). GO and KEGG pathway analyses showed that the 39 target genes mainly enrichment in protein binding, cytoplasm and MAPK signaling pathway. Our six-miRNA-based model is a reliable prognostic tool for survival prediction and provides information for individualized treatment decisions in BC patients.