Cell-free microRNAs as non-invasive biomarkers in glioma: a diagnostic meta-analysis

Objective: Since the diagnostic value of microRNAs for detecting glioma is contentious, we aimed to carry out a meta-analysis to synthetically evaluate the diagnostic significance of cell-free microRNAs in cerebrospinal fluid and blood in the detection of glioma. Methods: A systematic document retrieval of public databases was performed to obtain eligible studies. Specificity was applied to draw the summary receiver operator characteristic (SROC) curve against sensitivity, and the pooled diagnostic efficiency was assessed by generating the area under the SROC curve. Meta-regression and subgroup analyses were utilized to explore the latent sources of heterogeneity. STATA 12.0, RevMan 5.3 and Meta-DiSc 1.4 were used to conduct all statistical analyses. Results: A total of 47 studies from 20 articles comprising 2262 glioma patients and 1986 controls were included in our meta-analysis. Cell-free microRNAs exhibited relatively good diagnostic efficiency in glioma detection, with a sensitivity of 0.83, a specificity of 0.87, and an area under the curve of 0.91. Cell-free miR-21 performed best with pooled area under the curve of 0.88, followed by miR-125 and miR-222. Subgroup analyses and meta-regression indicated that there was substantial heterogeneity existing among the studies, which was in part caused by sample size, World Health Organization grade, reference gene, microRNA origin (extracellular vesicles or non-extracellular vesicle-based-microRNA), microRNA profiling (single- or multiple-microRNA), specimen types, and ethnicity. Conclusions: Cell-free microRNAs in cerebrospinal fluid and blood may play an important role as promising non-invasive biomarkers in the early diagnosis of glioma. Further comprehensive forward-looking research is required to validate their clinical significance in glioma diagnosis.