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

Abstract

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-1405p as non-invasive liquid biopsy biomarkers. This study enrolled 50 breast cancer patients (25 primary nonmetastatic and 25 metastatic patients), and 15 control subjects. The expression of miR-20a and miR-140-5p was measured using qRT-PCR. Serum level of vascular endothelial growth factor (VEGF) was determined by ELISA. The predictive value of the studied markers was examined by Receiver-operating characteristics (ROC) curve analysis. MiR-20a was significantly upregulated, miR-140-5p downregulated, together with elevated serum VEGF levels in all breast cancer patients in comparison to controls and 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 were associated with positive lymph node metastasis (p<0.05) and correlated with VEGF levels (p<0.0001). In 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.