A two-miRNA signature of upregulated miR-185-5p and miR-362-5p as a blood biomarker for breast cancer

Abstract

Background: Differentially expressed microRNAs (miRNAs) in the blood of breast cancer patients may serve as diagnostic biomarkers.

Methods: In this study, miRNA microarray of the blood of breast cancer patients and healthy controls was performed. Candidate differentially expressed miRNAs were further verified by real-time polymerase chain reaction in 68 breast cancer patients and 13 healthy controls.

Results: Six upregulated blood miRNAs (miR-26b-5p, miR-106b-5p, miR-142-3p, miR-142-5p, miR-185-5p, and miR-362-5p) were identified in breast cancer patients. These six miRNAs could discriminate breast cancer patients from healthy controls, with areas under the receiver operating characteristic curve (AUCs) of 0.8891, 0.8158, 0.8529, 0.8507, 0.9050, and 0.9333, respectively. Bioinformatic analysis showed that the six miRNAs were potentially involved in numerous cancer-related pathways, including the mitogen-activated protein kinase signaling pathway, nuclear factor-kappa B signaling pathway, and the transforming growth factor-beta signaling pathway. Importantly, two miRNAs (miR-185-5p and miR-362-5p) were used to construct a two-miRNA panel by logistic regression. The two-miRNA panel displayed a better diagnostic performance than each of the miRNAs alone, with a higher AUC (0.957), sensitivity (92.65 %), and specificity (92.31 %). Additionally, the high expression of the six miRNAs or the two-miRNA panel was associated with poor prognosis of breast cancer.

Conclusions: We identified six upregulated miRNAs and a two-miRNA panel in the blood as potential biomarkers for the diagnosis and prognosis of breast cancer.

Keywords: Blood biomarkers; Breast cancer; Diagnosis; Prognosis; microRNA.