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

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.

Prognostic and Clinicopathological Significance of MiR-155 in Breast Cancer: A Systematic Review

“…Moreover, Huang et al [29] observed a significant decrease in miR-155 expression after treatment with the chemoterapic agent vinorelbune, suggesting miR-155 as a potential monitoring marker of clinical outcome. Similar results were reported also by Khalighfard et al [30] and Anwar and colleagues [37]. They proposed miR-155 as a biomarker for monitoring treatment response as its plasma levels were significantly downregulated after treatments.…”

“…On the contrary, Wang et al [22] found that serum miR-155 overexpression correlated with ER/PR-negative status. Similar discrepancies were found when other tumour parameters were assessed: Swellam et al [35] and Wang et al [22] found that serum miR-155 correlated with grade, whereas Jurkovicova et al [26] and Anwar et al [37] did not find this correlation. Regarding the TNM stage, five studies [25,27,29,30,35] reported that increased expression of circulating miR-155 was significantly associated with advanced stage, whereas the other four studies [23,30,31,37] did not find any correlations.…”

“…More concordant results have correlated miR-155 expression with therapeutic response [24,29,37]. In fact, in those studies, the authors found that circulating miR-155 decreased after treatment (surgical or pharmacological).…”

“…In single studies, circulating miR-155 was significantly associated with Ki-67 [26] and with TNBC [32]. Concerning the miR-155 association with tumour BC subtype, Lukiana et al found a significant correlation with TNBC subtypes, but opposing this were the results obtained by Anwar and colleagues [37]. Nevertheless, Zaleski et al [28] tested the diagnostic and prognostic relevance of miR-155 in serum of 103 BC subjects and did not find any clinical implications.…”

“…The studies focusing on the deregulation of miR-155 in blood samples of BC patients with prognostic factors provide heterogeneous results. Regarding tumour size, Answar et al [37] assessed the relationship between circulating miR-155 and tumour size, finding a significantly higher miR level in BC patients with tumours larger than 5 cm, whereas Jukovicova et al [26] and Soleimanpour et al [31] found no significant association. Concerning tumour hormonal status, Swellam et al [35] and Jurkovicova et al [26] did not find any significant correlations among serum and plasma miR-155 and ER/PR status, respectively.…”