Extracellular vesicle biomarkers for prostate cancer diagnosis: A systematic review and meta-analysis

Extracellular vesicle (EV) biomarkers have promising diagnostic and screening capabilities for several cancers, and growing evidence indicates that EV biomarkers can be used as diagnostic markers for prostate cancer (CaP). However, data on the diagnostic accuracy of EV biomarkers for CaP diagnosis are conflicting. We performed a systematic review and meta-analysis, aimed to summarize the diagnostic performance of EV biomarkers for CaP. We systematically searched PubMed, Medline, and Web of Science from inception to 12 September 2022 for studies that assessed the diagnostic accuracy of EV biomarkers for CaP. We summarized the pooled sensitivity and specificity calculated using a random-effects model. We identified 19 studies involving 976 CaP patients and 676 noncancerous controls; one study conducted independent validation tests. Ten studies emphasized EV RNAs, 6 on EV proteins, and 9 on biomarker panels. MiR-141, miR-221, and PSMA were the most frequently reported RNAs and proteins for CaP diagnosis. For individual RNAs and proteins, the pooled sensitivity and specificity were 70% (95% CI: 68%-71%), 79% (95% CI: 77%-80%), 85% (95% CI: 81%-87%), and 83% (95% CI: 80%-86%), respectively. The pooled sensitivity and specificity of the EV panels were 84% (95% CI: 82%-86%) and 86% (95% CI: 84%-88%), respectively. The studies may have been somewhat limited by the EV isolation and detection techniques. EV biomarkers showed promising diagnostic capability for CaP. Addressing deficiencies in EV isolation and detection techniques has important implications for the application of these novel noninvasive biomarkers in clinical practice.