Clinicopathologic significance and prognostic value of circRNAs in osteosarcoma: a systematic review and...

Osteosarcoma is the most prevalent malignant osseous sarcoma in children and adolescents, whose prognosis is still relatively poor nowadays. Recent studies have shown the critical function and potential clinical applications of circular RNAs (circRNAs) in osteosarcoma. Our review aimed to perform an updated meta-analysis to explore their clinicopathologic significance and prognostic value.

The structured literature was conducted via eight electronic databases and four gray literature sources until 20 Feb 2021 to identify eligible studies. The data was extracted directly from the articles or reconstructed based on Kaplan-Meier curves. The Newcastle-Ottawa Scale (NOS) tool was used to assess study quality. The clinicopathologic significance of circRNAs was measured through odds ratios (ORs) and their 95% confidence intervals (CIs), while the prognostic value was evaluated through hazard ratios (HRs) and their 95% CIs of overall survival (OS) and disease-free survival (DFS). Heterogeneity and publication bias were assessed. Sensitivity analyses were conducted. Subgroup analyses were performed according to study characteristics. An additional analysis was performed to investigate the relation between circ_0002052 and osteosarcoma.

Fifty-two studies were identified, in which 38 on clinicopathologic features and 36 on survival prognosis were included in quantitative analysis. The overall study quality was moderate with a median NOS score of 5.5 stars (range 3 to 8). For clinicopathologic features, dysregulated circRNAs were related to larger tumor size (OR 2.122, 95%CI 1.418-3.175), advanced clinical stage (OR 2.847, 95%CI 2.059-3.935), and present of metastasis (OR 2.630, 95%CI 1.583-4.371). For chemotherapy, dysregulated circRNAs suggest a better response (OR 0.443, 95%CI 0.231-0.849), but a higher probability of resistance (OR 9.343, 95%CI 5.352-16.309). For survival prognosis, dysregulated circRNAs were significantly correlated with poor OS (HR 2.437, 95%CI 2.224-2.670) and DFS (HR 2.125, 95%CI 1.621-2.786). The results did not show differences among subgroups. Higher circ_0002052 expression showed a relation with poor OS (HR 3.197, 95%CI 2.054-4.976).

Our review demonstrated that abnormally expressed circRNAs have a relation with advanced clinicopathologic features and better response, but a higher probability of resistance and poor survival prognosis in osteosarcoma patients. However, more studies are encouraged to provide more robust evidence to translate circRNAs into clinical practice.

PROSPERO ID: CRD42021235031.