A pair-wise meta-analysis highlights circular RNAs as potential biomarkers for colorectal cancer

Background: Circular RNAs (circRNAs) have emerged as a special subset of endogenous RNAs that are implicated in tumorigenesis and cancer progression. Herein we aim to carry out a meta-analysis to evaluate the clinicopathologic, diagnostic and prognostic significance of circRNA expression in colorectal cancer (CRC). Methods: A systematic search of online databases was performed for original articles published in English, which investigated the diagnostic accuracy, prognostic utility, and clinicopathologic association of circRNA(s) in CRC. Data were strictly extracted and study bias was judged using the Quality Assessment for Studies of Diagnostic Accuracy II (QUADAS II) and Newcastle-Ottawa Scale (NOS) checklists. Results: A total of 13 studies, involving 1430 patients with CRC, were included in the meta-analysis. The clinicopathologic study showed that abnormally expressed circRNAs were correlated with tumor diameter (P = 0.0350), differentiation (P = 0.0038), lymphatic metastasis (P = 0.0119), distant metastasis (P < 0.0001), TNM stage (P = 0.0002), and depth of invasion (P = 0.001) in patients with CRC. The summary area under the curve (AUC) of circRNA for the discriminative efficacy between patients with and without CRC was estimated to be 0.79, corresponding to a weighted sensitivity of 0.77 [95% confidence interval (CI): 0.74-0.79], specificity of 0.67 (95%CI: 0.64-0.70), and diagnostic odds ratio (DOR) of 7.52 (95%CI: 4.66-12.12). Survival analysis showed that highly expressed circRNAs were correlated with significantly worse overall survival (OS) [hazard ratio (HR) = 2.66, 95% CI: 2.03-3.50, P = 0.000; X-2 = 4.34, P = 0.740, I-2 = 0.0%], whereas lower expression of circRNAs was associated with prolonged OS (weighted HR = 0.30, 95%CI: 0.17-0.53, P = 0.000; X-2 = 1.34, P = 0.909, I-2 = 0.0%). Stratified analysis in circRNA expression status, and test matrix also showed robust results. Conclusion: Abnormally expressed circRNAs may be auxiliary biomarkers facilitating CRC diagnosis, and promising prognostic biomarkers in predicting the survival of CRC patients.