<b>Circulating MicroRNA Profiles as Early Indicators of Breast Cancer Metastatic Potential</b>

Background: Breast cancer outcomes are strongly influenced by metastatic progression, and conventional clinicopathological features may not fully reflect tumor aggressiveness. Circulating microRNAs are stable, blood-based molecules that may provide non-invasive molecular information about metastatic potential. Objective: To compare circulating microRNA expression patterns between localized and metastatic breast cancer patients and assess their discriminatory value as candidate non-invasive biomarkers. Methods: This laboratory-based comparative study included 80 female patients with histologically confirmed breast cancer at a tertiary care hospital in Sialkot, Pakistan. Patients were divided into localized breast cancer (n=40) and metastatic breast cancer (n=40) groups. Clinical and pathological data were recorded. Peripheral blood samples were collected and circulating microRNAs were extracted from serum or plasma. Expression levels of miR-21, miR-10b, miR-155, miR-200c, miR-31, miR-126, and miR-335 were measured using reverse transcription quantitative real-time polymerase chain reaction. Relative expression was compared between groups, and discriminatory performance was assessed using receiver operating characteristic curve analysis. Results: Metastatic cases showed significantly higher expression of miR-21, miR-10b, miR-155, and miR-200c compared with localized cases, while miR-31, miR-126, and miR-335 were significantly reduced (p<0.001 for all). miR-10b showed the highest fold increase in metastatic disease, followed by miR-21. Grade III tumors and lymph node-positive cases showed more frequent alterations in miR-21, miR-10b, and miR-155 expression. miR-21 alone showed good discriminatory performance, with an area under the curve of 0.86. A combined microRNA panel showed stronger performance, with an area under the curve of 0.92, sensitivity of 87.5%, and specificity of 85.0%. Conclusion: Circulating microRNA profiles differed clearly between localized and metastatic breast cancer patients. Increased miR-21, miR-10b, miR-155, and miR-200c, together with reduced miR-31, miR-126, and miR-335, formed a candidate non-invasive biomarker pattern associated with metastatic disease. Larger longitudinal studies are needed to validate their prognostic value.