Diagnostic accuracy of circulating exosomal circRNAs in malignances: A meta-analysis and systematic review

Abstract

Background: Pathogenesis of malignant tumors are often accompanied by aberrant expression of circular RNAs (circRNAs), indicating the potential diagnostic value of circRNAs in tumors. CircRNAs have been found to be enriched, stable and ubiquitous in serum and plasma exosomes. The study aims at evaluating the diagnostic performance of circulating (plasma and serum) exosomal circRNA in different types of cancer by synthesis of published data.

Methods: A comprehensive literature search was conducted in PubMed, Embase, Medline and the Web of Science databases to identify potentially eligible studies published before April 2021. We conducted the meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.

Results: Eleven articles comprising 21 studies were included, and a total of 1609 cases and 1498 controls were evaluated. Six types of cancer were involved in these studies, including lung cancer, hepatocellular carcinoma, colorectal cancer, gastric cancer, multiple myeloma and osteosarcoma. The pooled sensitivity and specificity were 0.72 (95% confidence interval [CI], 0.62-0.81) and 0.83 (95% CI, 0.78-0.88), respectively. Summary receiver operating characteristic curve was constructed and the pooled value of area under curve was 0.86 (95% CI, 0.83-0.89), indicating a favorable diagnostic efficacy of circulating exosomal circRNAs in malignancies.

Conclusions: In conclusion, our study evaluated the diagnostic power of circulating exosomal circRNAs in 6 types of cancer by synthesis of published data comprising 21 studies from eleven articles. The pooled analysis provided the evidence supporting circulating exosomal circRNAs as a promising noninvasive diagnostic biomarkers for malignancies.

Figure 1.

Flow chart of selection process for eligible studies.

Figure 2.

Overall quality assessment of all included articles using the QUADAS-2 tool.

Figure 3.

Heterogeneity test of all included studies by bivariate boxplot.

Figure 4.

Forest plot of sensitivity and specificity for the diagnosis of circulating exosomal circRNA in malignancies.

Figure 5.

Forest plot of DLR+ and DLR− for the diagnosis of circulating exosomal circRNA in malignancies. DLR = diagnostic likelihood ratio.

Figure 6.

Forest plot of diagnostic score and diagnostic odds ratio of circulating exosomal circRNA in malignancies.

Figure 7.

The SROC curve and pooled AUC value for the diagnosis of circulating exosomal circRNA in malignancies. AUC = area under the curve, SROC = summary receiver operator characteristic.

Figure 8.

The assessment of publication bias among the included studies by Deek’s funnel plot asymmetry test.

Figure 9.

The estimating of the clinical significance in malignance diagnosis of circulating exosomal circRNA by Fagan plot.

Figure 10.

The likelihood ratio scattergram to estimate the clinical significance in malignance diagnosis of circulating exosomal circRNA.