Combination of Exosomal MiRNA Markers with BI-RADS for Accurate Diagnosis of Breast Tumor

Abstract Background Early and accurate identification of breast masses is of vital importance in clinic. Ultrasound imaging is an efficient strategy for breast mass screening, while the accuracy needs further improvement. Plasma exosomes have recently been suggested as promising candidate as disease markers. In this study, we aimed to explore the potential of plasma exosomal miRNAs in differentiation of breast masses. Methods Plasma exosomes were collected from patients with benign or malignant breast masses using a novel, facile, low-cost, and effective method of sequential salting-out and polyethylene glycol (PEG)-based approaches. Plasma exosomal miRNAs were extracted and profiled by RNA sequencing. Differential exosomal miRNAs were then tested by qPCR for screening of potential biomarkers. The diagnostic efficiencies of exosomal miRNAs alone or in combination with breast imaging reporting and data system (BI-RADS) in differentiation of breast masses were evaluated on a validation cohort via analysis of receiver operating characteristic (ROC) curve. Results Prior salting-out strategy yielded exosomes with higher purity, thus guaranteeing the accuracy of exosome-based diagnosis. miRNA sequencing showed different exosomal miRNA expressions between patients with malignant or benign breast masses, among which, hsa-miR-423-5p, hsa-miR-103a-3p and hsa-let-7i-5p were chosen and tested for diagnostic ability. ROC curve showed that these three miRNAs could serve as promising biomarkers, with hsa-miR-423-5p showing the highest diagnostic efficiency. Combination of exosomal miRNAs with BI-RADS further improved the diagnostic efficacy. Conclusions Plasma exosomal miRNAs could serve as excellent biomarkers for breast mass diagnosis and could significantly improve diagnostic accuracy when combined with BI-RADS.