Dynamic Changes of Circulating Mir-155 Expression and the Potential Application as a Non-Invasive Biomarker in Breast Cancer

Document Type: Research Articles

Authors

1 Division of Surgical Oncology - Department of Surgery, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

2 Graduate Program, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

3 PT Etana Biotechnologies Indonesia, Jakarta, Indonesia.

4 Medical Laboratory Technology, Health and Nursing Faculty, Universitas Muhammadiyah Semarang, Semarang, Indonesia.

5 Fakultas Ilmu Kesehatan, Universitas Setia Budi, Surakarta, Indonesia.

6 Politeknik Kesehatan Kemenkes Banjarmasin, Banjarmasin, Indonesia.

7 Departement of Pharmacology and Therapy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

8 Department of Histology and Cell Biology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

Abstract

Background: Breast cancer incidence rates have been continuously increasing in majority nations with significant higher portion of cancer-related mortality in low- and middle-income countries. Developing new biomarker is an emerging field in the breast cancer research. Application of a promising minimally invasive biomarker, circulating microRNA, for additional improvement of diagnosis, prognosis, and therapeutic monitoring in breast cancer is not well corroborated. Materials and Methods: To uncover the potential use of circulating miR-155 expression as a clinical biomarker in breast cancer, we analyzed 102 breast cancer patients at diagnosis and after treatment as well as 15 healthy women. Total RNA was isolated from patient’s plasma and expression of circulating miR-155 was measured with quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression levels of circulating miR-155 were compared according to the effect of treatment, clinicopathological variables, and progression-free survival.  Results: In comparison to the healthy women, expression of circulating miR-155 levels were significantly higher (medians were 18.49±19 and 1.28±0.18, respectively; p<0.0001). The expression levels of miR-155 were significantly diminished after patients completed surgery and chemotherapy (medians were 18.49±19 at diagnosis and 1.32±0.22 after treatment, respectively; p<0.0001). Patients older than 40 years old expressed higher circulating miR-155 than those younger than 40 years-old (medians were 28.92±22 and 4.19±2.49, respectively; p<0.0001). Circulating miR-155 was significantly higher in patients with tumors larger than 5 cm (44.27±2.6 vs 9.17±6.9, p=0.03). MiR-155 expression levels were not significantly different according to various tumor grades, subtypes, and clinical stages. Although longer follow-up is required, progression-free survivals of patients with upregulation of circulating miR-155 were significantly longer (mean survivals were 77 and 65 weeks, Log-rank (Mantel-Cox) test p=0.038). Conclusion: Expression of circulating miR-155 expression was significantly elevated in breast cancer patients and was decreased after treatment. Therefore, circulating miR-155 is potentially applicable as diagnostic therapeutic monitoring marker in breast cancer.
 

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