Circulating miR-34a and miR-125b as Promising non Invasive Biomarkers in Egyptian Locally Advanced Breast Cancer Patients

Abstract

Background: Breast cancer (BC) is the second most common cancer worldwide. MicroRNAs are a group of<br />non-coding, single stranded RNAs of ~ 22 nucleotides, which regulate gene expression at the post-transcriptional level.<br />Circulating miRNAs have been found as potential blood based predictive biomarkers. Purpose: we aim to evaluate<br />miR-34a and miR-125b to predict outcome from neoadjuvant chemotherapy in Egyptian BC patients. Methodology:<br />Quantitative assessment of plasma miR-34a and miR-125b expression was performed by qRT-PCR. Thirty nine<br />newly diagnosed locally advanced BC female patients with 10 age and sex matched healthy volunteers were included<br />in the study. Results: We performed ROC curve analysis to evaluate the diagnostic value for the miR-34a with<br />AUCs = 0.995, cutoff point of 2.57 sensitivity 97.4%, specificity 100%, PPV 100%, NPV 83.3% and accuracy 97.7%.<br />miR-125b had AUC = 0.68 and a cutoff point of 8.69 with sensitivity 66.7%, specificity 70.0%, PPV 90.6%, NPV<br />41.2% and accuracy 73.5%. miR-34a expression were significantly higher in BC patients compared to controls with p<br />value <0.001*. Also, miR-34a expression level was significantly higher in patients with progressive disease with P value<br />=0.03*. However, miR-125b expression levels were insignificantly higher in responsive patients with p value = 0.2.<br />Conclusion: miRNAs are crucial candidates for novel molecular targeted therapies due to their capability to regulate<br />numerous genes in molecular pathways. Our data suggest that circulating miR-34a and miR-125b expression levels<br />could be promising highly accurate non-invasive biomarkers in diagnosing BCs. miR-34a can predict chemotherapeutic<br />resistance associated with higher expression levels in non-responsive patients.