Abnormally expressed circular RNAs as novel non-invasive biomarkers for hepatocellular carcinoma: A meta-analysis

BACKGROUND: Circular RNAs (circRNAs) are a newly discovered class of endogenous non-coding RNAs that may have roles in cancer genesis and development. In the recent literature, dysregulated circRNAs have been extensively investigated in hepatocellular carcinoma (HCC). Whether or not circRNAs are of clinical value for the management of HCC has not been characterized. AIM: To meta-analyze the diagnostic and prognostic value of abnormally expressed circRNAs in HCC. METHODS: Eligible studies were sourced from PubMed, EMBASE, and CNKI online databases. Data on patients’ clinical characteristics, including diagnostic efficacy and overall survival, were extracted. The diagnostic and prognostic parameters were respectively synthesized using the bivariate meta-analysis model and multivariate Cox hazard regression analysis based on Stata 12.0. The trim and fill method was adopted to assess the possible effects from publication bias. RESULTS: A total of 21 eligible studies were included. The pooled sensitivity, specificity, and area under the curve of abnormally expressed circRNAs in distinguishing HCC from non-cancer controls were 0.78 (95%CI: 0.69–0.85), 0.80 (95%CI: 0.74–0.86), and 0.86, respectively. Survival analyses showed that the down-regulated circRNA expression signature correlated perfectly with HCC survival [hazard ratio (HR) = 0.42, 95%CI: 0.19–0.91, P = 0.028; I(2) = 92.7%, P = 0.000], whereas the HCC cases with high circRNA levels had significantly poorer prognoses than those of patients with low circRNA levels (HR = 2.22, 95%CI: 1.50–3.30, P = 0.000; I(2) = 91%, P = 0.000). Moreover, abnormally expressed circRNAs were intimately associated with tumor size, differentiation grade, microvascular invasion, metastasis, TNM stage, and serum alpha fetal protein level in patients with HCC. Stratified analysis based on sample type, control source, and expression status also yielded robust results. CONCLUSION: Abnormally expressed circRNA signatures show immense potential as novel non-invasive biomarker(s) for HCC diagnosis and prognosis.