Prognostic and clinicopathological significance of microRNA-21 overexpression in breast cancer: a meta-analysis

Abstract

Recent studies have highlighted the role of microRNA-21 (miR-21) as a prognostic biomarker of breast cancer. However, controversy still remains. The present study aimed to summarize available evidences and obtain a more precise estimation of a prognostic role of miR-21 in breast cancer patients. All eligible studies were searched from PubMed and EMBASE through multiple search strategies. Data were extracted from studies comparing survival in breast cancer patients having higher miR-21 expression with those having lower expression. A meta-analysis was performed to clarify prognostic role of miR-21 in patients with breast cancer. Subgroup analysis was also performed according to patients' ethnicity. A total of 6 eligible articles comprising 951 cases were selected for this meta-analysis. The combined hazard ratios (HRs) and 95% confidence intervals (95% CIs) for overall survival (OS) were 2.11 (1.09-4.08) and for disease free survival (DFS) was 1.6 (1.30-1.96). Subgroup analysis indicated high miR-21 expression was significantly associated with worse OS in Asian patients (HR = 4.39, 95% CI: 2.47-7.80) but not in non-Asian patients (HR = 1.18, 95% CI: 0.81-1.70). Sensitivity analysis revealed results of this meta-analysis were robust. Odds ratios (ORs) showed that miR-21 expression was closely associated with estrogen receptor (ER), progesterone receptor (PR), lymph node metastasis, histological grade, Her2/neu. The pooled ORs and 95% CIs were 0.53 (0.35-0.80), 0.49 (0.32-0.74), 2.32 (1.54-3.50), 2.44 (1.58-3.75), 4.29 (2.34-7.85), respectively. Our results indicated that elevated miR-21 expression could potentially predict poor survival in patients with breast cancer.

Keywords: MicroRNA-21; biomarker; breast cancer; meta-analysis; prognosis.

Figure 1

Flow diagram of the study selection process.

Figure 2

Forest plot of studies evaluating hazard ratio (HR) for the association of high miR-21 expression with overall survival (OS) (A) and disease-free survival (DFS) (B) in patients with breast cancer patients.

Figure 3

Forest plot of studies evaluating hazard ratio (HR) for the association of high miR-21 expression with overall survival (OS) stratified according to source of ethnicity.

Figure 4

Forrest plot of odds ratios (ORs) for the association of miR-21 expression with clinicopathological features in breast cancer. A. ORs with corresponding 95% CIs of miR-21 expression with Estrogen Receptor (ER). B. ORs with corresponding 95% CIs of miR-21 expression with Progesterone Receptor (PR). C. ORs with corresponding 95% CIs of miR-21 expression with lymphnode metastasis. D. ORs with corresponding 95% CIs of miR-21 expression with Histologic grade. E. ORs with corresponding 95% CIs of miR-21 expression with HER2/neu. F. ORs with corresponding 95% CIs of miR-21 expression with age.

Figure 5

A: Funnel Plots of elevated miR-21 expression and OS in patients with breast cancer. B: Funnel Plots of elevated miR-21 expression and DFS in patients with breast cancer.