MicroRNA-21 Identified as Predictor of Cancer Outcome: A Meta-Analysis

Background: Growing evidence from recent studies has revealed the association of microRNA-21 (mir-21) with outcomes in multiple cancers, but inconsistent findings have been reported, which rationalized a summary and analysis of available data to investigate the prognostic role of mir-21. Materials and Methods: Eligible studies were identified through several search strategies and assessed for quality. Data was extracted from studies in terms of baseline characteristics and key statistics such as hazard ratio (HR), 95% confidence interval (CI) and P value, which were utilized to calculate pooled effect size. Results: 25 studies were included in the meta-analysis to evaluate the prognostic role of mir-21 in malignant tumors. Elevated mir-21 level was demonstrated to moderately predict poor overall survival (OS) (HR = 1.903, 95% CI: 1.713-2.113, P = 0.000) and disease-free survival (DFS) (HR = 1.574, 95% CI: 1.139-2.175, P = 0.006) by the fixed and random effect model respectively. Importantly, subgroup analysis disclosed significant association between increased mir-21 level in cancerous tissue and worse survival status. Furthermore, over-expression of mir-21 was an independent prognostic factor for nonsmall cell lung cancer (NSCLC) and pancreatic cancer patients, with the pooled HR being 2.153 (95% CI: 1.693-2.739, P = 0.000) and 1.976 (95% CI: 1.639-2.384, P = 0.000). Conclusions: Over-expression of mir-21, especially in cancerous tissue, was effectively predictive of worse prognosis in various carcinomas. Non-invasive circulating mir-21, however, exhibited modest ability to discriminate outcomes. Major concerns about mir-21 assay standardization and selection of specimen need to be fully addressed before its practical implementation in management of cancer.