Upregulation of Circulating MiR-21 Expression as a Potential Biomarker for Therapeutic Monitoring and Clinical Outcome in Breast Cancer

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.

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

“…Although expression of miR-155 in primary breast cancer tissue has been associated with the prognosis, limited study has reported the correlation of circulating miR-155 with clinical outcomes (Jang et al, 2017;Lü et al, 2017). In contrast to our previous study using circulating miR-21 (Anwar et al, 2019b), our current study showed that upregulation of circulating miR-155 was associated with better PFS. Although miR-155 is commonly associated as oncomir, our study showed the upregulation with better PFS.…”

Candidate circulating microRNAs as potential diagnostic and predictive biomarkers for the monitoring of locally advanced breast cancer patients

“…This study aims at evaluating the diagnostic and predictive role of the expression of some candidate miRs, including miR-10b, miR-21, miR-155, miR-181a, miR-145, and let-7a, in LABC. In agreement with previous findings, 40,45–52 we demonstrated that the expression of the oncomiR-10b, oncomiR-21, and oncomiR-181a was significantly increased in LABC patients, whereas tumor suppressor miR-145 and let-7a expressions were significantly down-regulated, compared to healthy subjects. Similarly, the dysregulation of serum miR-10b, miR-21, miR-125b, miR-145, miR-155, miR-191, and miR-382 in breast cancer patients has been reported by Mar-Aguilar et al, 53 who concluded that these seven miRs can be used as a biomarker in breast cancer.…”

How metformin affects various malignancies by means of microRNAs: a brief review

“…MiR-21 is one of the prominent up-regulated oncomiRs in many types of cancers such as breast cancer cells [ 26 , 27 ]. Metformin inhibits proliferation and metastasis via down-regulation of miR-21-5p in breast cancer cell lines.…”