Dysregulated Expression of Circular RNAs Serve as Prognostic and Clinicopathological Markers in Cancer

Purpose: Circular RNAs (circRNAs) as prognostic biomarkers have spurred considerable interest in several types of tumors. In the present study, we aimed to elucidate the clinicopathological and prognostic values of circRNAs in human cancer. Methods: We systematically searched PubMed Central (PMC), PubMed, Web of Science, EMBASE, Scopus, CBM and the Cochrane Library databases up to Nov 29, 2018. Eligible studies reporting on the association between circRNAs expression and clinicopathological and prognostic outcomes in cancer were incorporated. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess clinicopathological parameters, and hazard ratios (HRs) and 95% CIs to estimate overall survival (OS). Results: Thirty-two studies involving 4529 patients were incorporated into our meta-analysis. Pooled results showed that high expression of oncogenic circRNAs was significantly associated with poor clinicopathological characteristics (tumor size: OR=1.29, 95%Cl: 1.10-1.51; TNM stage: OR=1.62, 95%Cl: 1.41-1.87; differentiation grade: OR=1.41, 95%Cl: 1.11-1.78; lymph node metastasis: OR=1.69; 95%Cl: 1.34-2.13; distant metastasis: OR=2.75; 95%Cl: 1.92-3.95) and a poor prognosis (OS: HR=2.75; 95%Cl: 2.34-3.15). Furthermore, we found that high expression of tumor-suppressor circRNAs was correlated with improved clinical characteristics (tumor size: OR=0.72; 95%Cl: 0.56-0.92; TNM stage: OR=0.77, 95%Cl: 0.68-0.88) and longer survival times (OS: HR=0.49; 95%Cl: 0.42-0.56). Subgroup analyses based on cancer types and circRNA types were also performed. Conclusion: Our study indicates that circRNAs may serve as important biomarkers for clinicopathologic features and prognosis in human cancer.