Breast Cancer: Targets and Therapy (Jan 2021)

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

  • Purwanto I,
  • Heriyanto DS,
  • Widodo I,
  • Hakimi M,
  • Hardianti MS,
  • Aryandono T,
  • Haryana SM

Journal volume & issue
Vol. Volume 13
pp. 1 – 7

Abstract

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Ibnu Purwanto,1 Didik Setyo Heriyanto,2 Irianiwati Widodo,2 Mohammad Hakimi,3 Mardiah Suci Hardianti,1 Teguh Aryandono,4 Sofia Mubarika Haryana5 1Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia; 2Department of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia; 3Department of Clinical Epidemiology and Biostatistics Unit, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia; 4Department of Surgical Oncology, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia; 5Department of Histology and Cell Biology, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, IndonesiaCorrespondence: Ibnu PurwantoDivision of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Jalan Farmako, Sekip Utara, Yogyakarta 55281, IndonesiaTel/Fax (+62 274) 560300Email [email protected]: Determining 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 Methods: We 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.Results: The 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.Conclusion: Overexpression of miR-223 is associated with increased expression of EGFR, worse prognosis, and resistance toward platinum-based chemotherapy in Indonesian TNBC patients.Keywords: miR-223, chemotherapy, prognosis, EGFR, TNBC

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