Abstract
BACKGROUND: As circular RNAs (circRNAs) have been found to significantly involve in the onset and progression of multiple malignant tumors including breast cancer (BC), this study aims at evaluating the diagnostic and prognostic values of circRNAs in this malady. METHODS: Available databases were thoroughly searched to collect studies on the diagnosis and/or prognosis of BC using circRNA profiling. The updated Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool and the Newcastle Ottawa Scale (NOS) were used to assess the underlying bias of included studies. Clinical characteristics of the studies were merged by the quantitative-weighted integral method to obtain the combined effects. RESULTS: Sixteen studies were included, comprising 2438 BC cases and 271 noncancerous controls. The expression signature covered 24 circRNAs (down-regulated: circ-VRK1, hsa_circ_0068033, hsa_circ_103110, hsa_circ_104689, and hsa_circ_104821; up-regulated: circAGFG1, hsa_circ_0001785, hsa_circ_0108942, hsa_circ_0001785, hsa_circ_006054, hsa_circ_100219, hsa_circ_406697, circEPSTI1, circANKS1B, circGFRA1, circ_0103552, CDR1-AS, has_circ_001569, hsa_circ_001783, circFBXL5, circ_0005230, circAGFG1, circ-UBAP2, and circ_0006528). The sensitivity and specificity of circRNAs in distinguishing BC patients from noncancerous controls were 0.65 and 0.68, and the corresponding area under the curve was 0.66. Survival analysis revealed that patients showing highly expressed oncogenic circRNAs were associated with increased mortality risks of BC in overall survival (univariate analysis: hazard ratio [HR] = 3.30, P = .000; multivariate analysis: HR = 3.07, P = .000), and disease-free survival (HR = 8.26, P = .000). Stratified analysis based on circRNA expression status and control type also showed robust results. CONCLUSIONS: Circular RNA profiling presents prominent diagnostic and prognostic values in BC, and can be rated as a promising tool facilitating its early diagnosis and survival.