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

Abstract

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.

Circulating miR-20a and miR-26a as Biomarkers in Prostate Cancer

“…Porkka et al, (2007) identified 51 individual miRNAs which differentially expressed between benign and malignant tumors, among which, 37 showed down-regulation and 14 showed up-regulation in carcinoma samples. In other studies higher levels of miR-20a expression were shown in more dedifferentiated PCa cells (Pesta et al, 2010) and other cancers (Zhang et al, 2018). Ambs et al, (2008) suggested that microRNA expression changes with development and progression of prostate cancer and microRNAs regulated some of the cancer-related genes.…”

“…We selected miR-20a and miR-26a for analysis based on previous impellent studies which described the importance of these miRNAs in cancers (ParvizHamidi et al, 2018;Xu et al, 2018). For example there are studies expressed that miR-20a regulates cell growth and plays important roles in prostate and other cancers initiation and progression (O'donnell et al, 2005;Pesta et al, 2010;Liu et al, 2012;Xu et al, 2018;Zhang et al, 2018). Shen et al, (2012) represented significant overexpression of miR-20a in plasma from patients with stage 3 PCa tumors compared to stage 2 or below.…”

Overexpression of miR-20a-5p in Tumor Epithelium Is an Independent Negative Prognostic Indicator in Prostate Cancer—A Multi-Institutional Study

“…Zhang et al performed a systematic review where they evaluated the prognostic implication of miR-20a in PCa [34]. In this article, miR-20a was found to be upregulated in the circulatory system in PCa, and this was correlated with a worse OS [34]. They also found miR-20a upregulated in gastric cancer, glioblastoma, lymphoma and non-small-cell lung cancer (NSCLC), correlating with a worse OS and DFS [34].…”

“…Zhang et al performed a systematic review where they evaluated the prognostic implication of miR-20a in PCa [34]. In this article, miR-20a was found to be upregulated in the circulatory system in PCa, and this was correlated with a worse OS [34].…”

Prognostic significance of microRNA-135 in patients with digestive system cancers: a systematic review and meta-analysis

“…It was convincing that changes in miRNA expression and patient survival was consistent in both the peripheral blood and tissues. However, the results may differ on occasion; for example, when Zhang et al [48] elucidated the prognostic value of miR-20a in human cancers, high expression of both circulating and tumorous miR-20a were associated with an unfavorable outcome only in gastrointestinal cancers. In this meta-analysis, all the included studies were related to tissue miRNAs with reliable results.…”