Circulating miRNA 20a, miRNA 140-5p and VEGF as Predictive Biomarkers of Metastasis in Liquid Biopsy of Breast Cancer Patients

Abstract

Background: MicroRNAs (miRNAs) are critical modulators in breast carcinogenesis. Metastasis remains the underlying cause of breast cancer related mortality. We sought to elucidate the predictive potential of circulating miR-20a and miR-140-5p as non-invasive liquid biopsy biomarkers. Subjects and methods: The study comprised 50 breast cancer patients (25 primary non-metastatic and 25 metastatic patients), and 15 healthy controls. The expression of miR-20a, miR-140-5p was measured using qRT-PCR. Serum levels of vascular endothelial growth factor (VEGF) was determined by ELISA. The predictive value of studied markers was evaluated by Receiver-operating characteristics (ROC) curve analysis. Results: MiR-20a was significantly upregulated, miR-140-5p downregulated, together with elevated serum VEGF levels in all breast cancer patients compared to controls and in the metastatic compared to non-metastatic group (p < 0.001 for each). MiR-20a, miR-140-5p and VEGF exhibited significant predictive value for metastasis (AUC of 1 in all), with high specificity and sensitivity. MiR-20a and miR-140-5p expression was associated with lymph node involvement (p < 0.05) and correlated with VEGF levels (p < 0.0001). Conclusion: Our findings suggest that circulating miR-20a and miR-140-5p are promising non-invasive predictive biomarkers to discriminate between metastatic and locally-confined breast cancer. They may also hold a promise as targets for miRNA-based treatments.