MicroRNA-200 families and prognostic value in various carcinomas: A systematic review and meta-analysis

Abstract

Background: Recently, some studies have showed that miR-200 families act as novel biomarkers for the prediction of cancer outcomes.

Aims: This meta-analysis was designed to investigate the associations between miR-200 families and the prognosis of patients with various cancers.

Materials & methods: Eligible published databases including PubMed, Embase and Chinese National Knowledge Infrastructure (CNKI) databases were searched for articles until October 18, 2016. We performed a meta-analysis by calculating pooled hazard ratios (HR) and 95% confidence intervals (CI). Data were extracted from studies comparing overall survival (OS), progression-free survival (PFS) or recurrence-free survival (RFS).

Results: For OS, the pooled HR was 1.54 (95% CI: 1.01-2.33), showing that high miR-200 family was clearly related to poor survival in various carcinomas, but no significantly association was found in PFS or RFS. Subgroup analysis indicated that upregulated miR-200 family was linked to poor OS in Asians (HR = 2.19, 95% CI: 1.27-3.78) but not in Caucasians (HR = 0.94, 95% CI: 0.46-1.91). Similarly, high miR-200 expression could not clearly predict the relationship with PFS and RFS. For cancer type, high miR-200 also predicted poor OS among lung cancer patients (HR = 3.09, 95% CI: 1.75-5.46). Besides, only elevated miR-200c of the miR-200 family indicated a significantly poor OS (HR = 2.25, 95% CI: 1.39-3.64).

Discussion: Aberrant expression of miRNAs played a crucial role in the area of human carcinomas. Many studies have indicated that miRNAs are considered promising tumor biomarkers for prognosis and potential targets for clinical treatment. We have testified that high levels of miR-200 family expression (predominantly miR-200c) are significantly associated with poor survival and prognostic outcomes of patients with cancers, especially in lung cancer. However, no statistically significant results were calculated for miR-200a/b and miR-429, and this might result from a relatively small number of articles about them. In other tumor models except lung cancer, our results indicated that high miR-200 family was not obviously associated with OS (Gastric or Colorectal cancer; Ovarian cancer; Others). In addition, some other records showed the opposite results, for they exhibited that upregulated miR-200 family level was linked to longer survival. For ethnic group, our stratified analyses showed that the Asian population predicted poor OS. While the Caucasian population did not exhibit an significant association with OS. This discrepancy might result from different hereditary backgrounds and environment exposure. Although these results have indicated that miR-200 families were promising biomarkers to predict prognosis for patients with cancers, there were several limitations in this analysis that would impact its quality. Generally, further studies should be warranted to clarify this question and to provide a new novel idea for routine clinical application.

Conclusion: Our findings suggest that miR-200 family might be a potentially useful biomarker for predicting cancer prognosis, especially for lung cancer in Asians.

Keywords: biomarker; carcinoma; miR‐200 family; prognosis.

Figure 1

Flow diagram of the study selection process

Figure 2

Forest plots of total analyses for patient survival associated with miR‐200 family expression. The squares and horizontal lines correspond to study‐specific hazard ratio (HR) and 95% confidence interval (CI). The area of the squares reflects the weight. The diamond represents HR and 95% CI

Figure 3

Funnel plot of publication bias test for overall analysis of overall survival. Each point represents a separate study