Change of Circulating and Tissue-Based miR-20a in Human Cancers and Associated Prognostic Implication: A Systematic Review and Meta-Analysis

BACKGROUND: Previous literatures have investigated the change of miR-20a expression level in the progression of multiple cancers and its influence on patients' survival outcome, but results of now-available evidence are inconsistent. OBJECTIVE: To elucidate the prognostic value of circulating and tissue-based miR-20a for patients with various cancers. METHODS: A systematic search and review of eligible publications were carried out in three electronic databases including the Cochrane Library, PubMed, and Embase, and the methodological quality of included studies was assessed according to Newcastle-Ottawa Scale (NOS). Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS), and progressive-free survival (PFS) of each study were pooled using a random effect model. RESULTS: In total, 24 studies involving 4186 samples of multiple cancers published in 20 articles were included in the statistical analysis. As for circulating miR-20a, five kinds of cancers containing gastric cancer, lymphoma, glioblastoma, prostate cancer, and non-small-cell lung cancer reported upregulated level in patients compared with normal healthy control, and overexpressed circulating miR-20a could confer an unfavorable factor for OS (HR = 1.71, 95% CIs: 1.43 -2.04, p < 0.01) and DFS (HR = 1.90, 95% CIs: 1.45-2.49, p < 0.01). As for tissue-based samples, 6 kinds of malignancies including colorectal cancer, salivary adenoid cystic carcinoma, gallbladder carcinoma, colon cancer, gastrointestinal cancer, and alveolar rhabdomyosarcoma revealed upregulated miR-20a expression level compared with paired nontumorous tissue, of which high expression of miR-20a was significantly associated with poor OS (HR = 2.74, 95% CIs: 1.38-5.42, p < 0.01) and DFS (HR = 2.68, 95% CIs: 1.32-5.45, p < 0.01); meanwhile, other 5 tumors containing breast cancer, cutaneous squamous cell carcinoma, hepatocellular carcinoma, oral squamous cell carcinoma, and epithelial ovarian cancer demonstrated downregulated miR-20a expression level compared with benign tissue, of which low miR-20a expression was significantly related to shorter OS (HR = 3.48, 95% CIs: 2.00-6.06, p < 0.01) and PFS/RFS (HR = 4.05, 95% CIs: 2.89-5.66, p < 0.01). CONCLUSION: Change of circulating and tissue-based miR-20a expression possesses vital prognostic implication for human cancers. Augmented expression of circulating miR-20a predicts poor survival outcome for patients with cancers. Tissue-based miR-20a level may be upregulated or downregulated depending on cancer types; in the former condition, high expression of tissue miR-20a is a risk factor for unfavorable prognosis and in the latter condition low expression of tissue miR-20a is associated with shorter survival.