Upregulation of Circulating MiR-21 Expression as a Potential Biomarker for Therapeutic Monitoring and Clinical Outcome 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 Faculty of Health Sciences, Setia Budi University, Surakarta, Indonesia.

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

5 Current position: PT Etana Biotechnologies Indonesia, Jakarta, 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: Aberrant patterns of microRNA expression have been highlighted as a potential clinical biomarker in
breast cancer as the most frequent cancer among women that contributes nearly a quarter of total cancer incidence in
2018. Upregulation of microRNA-21 (miR-21) is associated with adverse clinical outcomes in breast cancer. However,
the use of circulating free miR-21 as a non-invasive biomarker for diagnosis and therapeutic monitoring in breast
cancer is not well established. We quantified the levels of circulating miR-21 expression and analyzed their correlation
with clinicopathological variables and progression-free survival. Materials and Methods: This initial study included
a cohort of 102 breast cancer patients of different subtypes and clinicat stages. We also included 15 unrelated healthy
women. Venous blood from patients was collected at diagnosis and after treatment of surgery and chemotherapy.
MiR-21 expression was quantified from total RNA fraction isolated from patient’s plasma. Quantitative reverse
transcription polymerase chain reaction (qRT-PCR) was used to analyzed miR-21 expression. Results: Expression of
circulating miR-21 was significantly elevated in breast cancer patients compared to healthy women (median miR-21
expression levels were 7.67±2.2 and 1.28±0.16, respectively; p<0.0001). Significant reduction of miR-21 expression was
observed in breast cancer patients after completion of surgery and chemotherapy (median miR-21 expression levels were
7.67±2.2 at diagnosis and 2.16±1.28 after treatment, respectively; p<0.0001). MiR-21 expression was higher in breast
cancer patients younger than 40-year-old but was not significantly different according to different histopathological
grades and clinical stages at diagnosis. Patients with upregulation of circulating miR-21 were associated with poor
progression-free survival (median survival 72 vs 86 weeks, respectively; log-rank (Mantel-Cox) test, p=0.049).
Conclusion: MiR-21 expression was upregulated in breast cancer patients and might serve as a therapeutic monitoring
marker.

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