Abnormally Expressed Circular RNAs as Novel Non-Invasive Biomarkers for Hepatocellular Carcinoma: A Pair-wise Meta-Analysis
Abstract Background: In the recent literature, dysregulated circular RNAs (circRNAs) have been extensively investigated in hepatocellular carcinoma (HCC). This study strives to evaluate the diagnostic as well as the predictive 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 (OS) 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 approach was employed to evaluate the impacts of publication bias. Results: A sum of 21 eligible types of research was incorporated. The pooled sensitivity, specificity and area under the curve (AUC) of abnormally expressed circRNAs in distinguishing HCC from non-cancer controls were estimated to be 0.78 (95% confidence interval (CI): 0.69–0.85), 0.80 (95% CI: 0.74–0.86) and 0.86, respectively. Survival analyses expressed 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; I2 = 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; I2 = 91%; p = 0.000). Moreover, abnormally expressed circRNAs were intimately linked with tumor size, differentiation grade, microvascular invasion, metastasis, TNM stage, and serum AFP level in patients with HCC. Stratified analysis based on sample type, control source, and expression status also yielded robust results. Conclusions: Abnormally expressed circRNA signatures show immense potential as novel non-invasive biomarker(s) in complementing HCC diagnosis and prognosis.