Prognostic Implications of microRNA-155, -133a, -21 and -205 in Breast Cancer Patients' Plasma

Abstract

Background: Breast cancer, being a heterogenous disease at the intra-tumoral and intertumoral levels, presents challenges in following the progress of the disease. Tumour-secreted aberrantly expressed miRNAs obtained from peripheral blood represent a non-invasive alternative resource for detecting and monitoring the development of the disease. This study evaluates the expression of miR-155, miR-133a, miR-21 and miR-205 as non-invasive, prognostic and follow-up markers for breast cancer.

Methods: Plasma expression levels of miR-155, miR-133a, miR-21 and miR-205 were measured using real-time PCR in breast cancer patients (n=63) at presentation, healthy controls (n=25), and in post-treatment samples of 31 patients. A meta-analysis was performed using 43 studies identified from PubMed, Google Scholar and Scopus databases. Hedge's g values were used to calculate the overall effect size.

Results: Plasma miR-21 levels were higher in breast cancer patients at presentation compared to controls, while no difference was observed for miR-155, miR-133a and miR-205. These results were further supported by the meta-analysis. The altered levels of miR-155 during tamoxifen treatment indicated a potential role for miR-155 in monitoring treatment response. Further, high expressions of at least three miRNAs correlated with poor overall survival in the breast cancer patients.

Conclusion: Plasma levels of miR-155, miR-133a, miR-21 and miR-205 may be useful as prognostic and follow-up markers for breast cancer with further validation in a large cohort of patients.

Keywords: Circulating miRNA; breast cancer; liquid biopsy; non-invasive biomarkers; plasma.; real-time PCR.