MicroRNA-223 is Associated with Resistance Towards Platinum-based Chemotherapy and Worse Prognosis in Indonesian Triple-negative Breast Cancer Patients.

Abstract

PurposeDetermining the optimal strategy to implement systemic treatment modalities has been challenging in triple-negative breast cancer (TNBC). We aim to investigate the role of microRNA-223 (miR-223) as prognostic factor and predictor of response toward chemotherapy in TNBC.Patients and MethodsWe retrospectively analyzed the association of pretreatment miR-223 expression with clinicopathologic characteristics and 36-month overall survival (OS) of 53 all stages TNBC patients. Tumor level of miR-223 was measured using real-time quantitative polymerase chain reaction (expressed in fold change). Cutoff value for miR-223 was determined by using receiver operating curve (ROC). Kaplan–Meier curve was used to perform survival analysis.ResultsThe optimum cutoff value for miR-223 was 23.435 (AUC: 0.706, 95%CI: 0.565–0.848; p:0.01; sensitivity: 78.6%; specificity: 56%) and was used to categorize mir-223 expression into over- and underexpressed group. Overexpression of miR-223 was associated with increased expression of EGFR (69.7% vs 35%, p: 0.022) and lower 36-month OS (33.3% vs 70%; median OS±SE (months): 25.66±1.58 vs 30.23±1.99; log rank p<0.05). Worse survival is observed in miR-223 overexpressed group receiving platinum-based chemotherapy compared to miR-223 underexpressed group (mean OS (95%CI) months: 24.7 (20.3–29.1) vs 34.3 (31.2–37.4); p<0.01), while no significant difference observed in non-platinum containing regimen. No significant association was observed between miR-223 expression with other clinicopathologic characteristics.ConclusionOverexpression of miR-223 is associated with increased expression of EGFR, worse prognosis, and resistance toward platinum-based chemotherapy in Indonesian TNBC patients.