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.<br />.

Keywords: Biomarker; MicroRNA; breast cancer; miR-155.

Figure 1

Circulating miR-155 Expression Levels in Breast Cancer Patients were Frequently Upregulated and were Significantly Higher Compared to Healthy Women. Medians of miR-155 expression levels were 18.49±19 and 1.28±0.18, respectively; p<0.0001

Figure 2

Expression Levels of Circulating miR-155 were Significantly Higher in Breast Cancer Patients Older than 40 Years-Old (median expression levels were 28.92±22 and 4.19±2.49, respectively; p=0.0009).

Figure 3

Expression Levels of Circulating miR-155 were not Significantly Different between Good/Moderate Differentiation (Grade I-II) and Poor Differentiation (Grade III) (median expression levels were 17.13±14 and 25.87±35, respectively; p=0.67)

Figure 4

Expression Levels of Circulating miR-155 were also not Statistically Different between Early Stages (Stadium I-II) and Late Stages (Stadium III-IV) (median expression levels were 17.13±15 and 31.62±13, respectively; p=0.52).

Figure 5

Significant Reduction of Circulating miR-155 Expression after Surgery and Chemotherapy. In comparison to the baseline, expression of circulating miR-155 was significantly reduced after treatment (medians were 18.49±19 and 1.32±0.22, p<0.0001)

Figure 6

Upregulation of Circulating miR-155 Correlated with Better Progression-Free Survival (PFS). MiR-155 upregulation in breast cancer patients is associated with longer progression-free survival (median PFSs were 77 vs 65 weeks, Mantel-Cox test p=0.038).