Exosome-Derived Long Non-Coding RNAs as Non-Invasive Biomarkers of Bladder Cancer.

Abstract Objective: As a result of the inconsistency between reports, a meta-analysis was designed to appraise the clinical implications of long non-coding RNAs (lncRNAs) in exosomes for the diagnosis of bladder cancer. Methods: The PubMed, EMBASE, and Cochrane library databases were searched to identify the relevant literature on lncRNAs in exosomes for bladder cancer diagnosis from database inception to May 2021. The literature was screened according to the inclusion and exclusion criteria, and the Quality Assessment of Diagnostic Accuracy Studies-2 entry tool was applied to evaluate the quality of the literature, and the sources of heterogeneity were explored using meta-regression and subgroup analysis. Stata 14.0 and RevMan 5.3 software were used for statistical analysis. Results: A total of 23 studies described in 10 articles were included, with a total of 1883 patients with bladder cancer and 1721 patients in the non-cancerous control group. The exosome-derived lncRNAs performed better in the diagnosis of bladder cancer with a pooled sensitivity of 0.74 (95% CI, 0.69-0.77), specificity of 0.76 (95% CI, 0.72-0.80), and area under the curve of 0.83. The heterogeneity between studies was partly as a result of differences in specimen type, number of lncRNAs, lncRNA expression form, and reference gene type. Subgroup analysis showed that the detection efficacy based on the combination of multiple lncRNAs (0.86, 95% CI, 0.82-0.88) was higher than that based on a single lncRNA (0.81, 95% CI, 0.78-0.85), and exosomal lncRNAs with blood as the detection sample had a high diagnostic efficacy (0.86, 95% CI, 0.82-0.86). Conclusions: Exosome-derived lncRNAs hold great promise as non-invasive diagnostic biomarkers of bladder cancer; however, their clinical value needs to be examined in further comprehensive prospective studies.