Diagnostic and Prognostic Significance of Dysregulated Expression of Circular RNAs in Osteosarcoma

Abstract

Background CircRNAs have emerged as pivotal regulators in osteosarcoma tumorigenesis and progression, but their prognostic and diagnostic significance remain unclear. Herein, we aimed to perform an updated meta-analysis to explore the clinical, diagnostic and prognostic values of circRNAs in osteosarcoma. Methods Several databases, including PubMed, Web of Science, EMBASE, Scopus and Cochrane Library, were systematically searched up to April 10, 2020. Eligible studies regarding the relationship between circRNAs levels and clinicopathological, diagnostic and prognostic values in osteosarcoma patients were included in this study. Pooled odds ratios with corresponding 95% confidence intervals were used to measure clinical characteristics, while hazard ratios with 95% CIs were adopted to assess overall survival (OS) and disease-free survival (DFS). Results Overall, 26 relevant studies involving 1,652 patients with osteosarcoma were enrolled, with eighteen studies on clinicopathological parameters, ten on diagnosis and eighteen on prognosis. For clinical parameters, overexpression of oncogenic circRNAs was intimately correlated with larger tumor size (P < 0.00001), advanced Enneking stage (P < 0.00001), poor differentiation (P = 0.0001), and distant metastasis (DM) (P < 0.00001). In contrast, the downregulated circRNAs showed negative correlation with Enneking stage (P = 0.002) and DM (P < 0.0001). For the diagnostic values, the summary area under the curve of circRNA for the discriminative efficacy between osteosarcoma patients and non-cancer counterparts was estimated to be 0.86 (95% CI: 0.83–0.89), with a weighted sensitivity of 0.80 (95% CI: 0.74–0.84), specificity of 0.80 (95%: 0.75–0.84), and diagnostic odds ratio of 15.48 (10.85–22.10), respectively. For the prognostic significance, oncogenic circRNAs had poor OS (HR = 1.92, 95% CI: 1.68–2.19) and DFS (HR = 2.65, 95% CI: 2.02–3.49), while elevated expression of tumor-suppressor circRNAs were closely related to longer OS (HR = 0.44, 95% CI: 0.28–0.69). Conclusions Taken together, our study showed that aberrantly expressed circRNA signatures could serve as potential biomarkers in diagnosis and prognosis in patients with osteosarcoma.