The potential diagnostic value of extracellular vesicle miRNA for human non-small cell lung cancer: a systematic review and meta-analysis.

Background The purpose of the meta-analysis is to evaluate the accuracy of extracellular vesicles (EV) miRNAs in the diagnosis of Non-small cell lung cancer (NSCLC). Methods All eligible studies were searched electronically online database. STATA15.0, Meta-disc14.0 and Review Manager 5.2 software were used to perform all statistical analysis. Results The analysis included 16 articles searched electronically online database and a total of 70 studies. Pooled sensitivity (SE) and specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) were 0.77 (95% CI: 0.72-0.80), 0.83(95% CI: 0.78-0.86), 0.88 (95% CI: 0.86-0.90) and 0.63 (95% CI: 0.58-0.68), respectively. The overall diagnostic odds ratio (DOR) were 16(95% CI: 11-21) and the area under the curve (AUC) was 0.86 (95% CI: 0.83-0.89). Threshold analysis showed there was no threshold effect (P=0.11). Meta-regression suggested specimen, publication year and sample size might be the major source of heterogeneity. Subgroup analysis hinted that combined test had better diagnostic accuracy for NSCLC than alone. Conclusion Circulating EV miRNAs are significantly associated with NSCLC diagnosis, especially metastatic NSCLC, followed by early NSCLC, whose AUC values were 0.90 and 0.88, respectively. 3 of EV miRNAs might act as biomarkers for metastatic NSCLC diagnosis, and 10 for early stage of NSCLC. EV miR-21, miR-210, and miR-1290 might be associated with PK13/AKT related pathway and be the valuable diagnostic biomarkers for NSCLC. Besides, multitudinous EV miRNAs combined to diagnose NSCLC show a higher diagnostic value than alone.