Three-microRNA expression signature predicts survival in triple-negative breast cancer.

Author information

1: Department of Thyroid and Breast Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China.

Abstract

Triple-negative breast cancer (TNBC) is a specific type of breast cancer with poor overall survival (OS) time. Previous studies revealed that microRNAs (miRNAs/miRs) serve important roles in the pathogenesis, progression and prognosis of TNBC. The present study analyzed the miRNA expression and clinical data of patients with TNBC downloaded from The Cancer Genome Atlas. A total of 194 differentially expressed miRNAs were identified between TNBC and matched normal tissues using the cut-off criteria of P<0.05 and |log2 fold change|>2. Of these miRNAs, 65 were downregulated and 129 were upregulated. Using Kaplan-Meier survival analysis, a total of 77 miRNAs that were closely associated with OS time were identified (P<0.05). The intersection of the 77 miRNAs and 194 differentially expressed miRNAs revealed six miRNAs. Log-rank tests based on survival curves were performed and two miRNAs were eliminated. The prognostic value of the remaining four miRNAs was evaluated with a Cox proportional hazards model using multiple logistic regression with forward stepwise selection of variables. Three miRNAs (miR-21-3p, miR-659-5p and miR-200b-5p) were subsequently identified as independent risk factors associated with OS time in the model. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that the target genes of these three miRNAs were mainly involved in 'cell protein metabolism', 'RNA transcriptional regulation', 'cell migration', 'MAPK signaling pathway', 'ErbB signaling pathway', 'prolactin signaling pathway' and 'adherens junctions'. Taken together, the results obtained in the present study suggested that the three-miRNA signature may serve as a prognostic biomarker for patients with TNBC.