Diagnostic and Prognostic Performance of Liquid Biopsy-Derived Exosomal MicroRNAs in Thyroid Cancer Patients: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Circulatory tumor-derived exosomal miRNAs play key roles in cancer development and progression. Studies have shown that serum and plasma miRNAs have the potential to be promising biomarkers for cancer diagnosis. This meta-analysis aimed to assess the diagnostic and prognostic performance of exosomal miRNAs in thyroid cancer. Our study analysis included 12 articles. We found that specific exosomal miRNAs found in blood provide high diagnostic value with high sensitivity and specificity. Furthermore, certain panels of exosomal microRNAs showed remarkable diagnostic value. The best discriminative ability to differentiate between cancer and non-cancer individuals were for miR-146b-5p + miR-223-5p + miR-182-5p. The novel and non-invasive use of miRNAs to diagnose TC can significantly improve patient outcomes by preventing the burden of unnecessary surgery and providing prognosis information on thyroid cancer. ABSTRACT: Circulatory tumor-derived exosomal microRNAs (miRNAs) play key roles in cancer development/progression. We aimed to assess the diagnostic/prognostic value of circulating exosomal miRNA in thyroid cancer (TC). A search in PubMed, Scopus, Web of Science, and Science Direct up to 22 May 2021 was performed. The true/false positive (TP/FP) and true/false negative (TN/FN) rates were extracted from each eligible study to obtain the pooled sensitivity, specificity, positive/negative likelihood ratios (PLR/NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (95%CIs). The meta-analysis included 12 articles consisting of 1164 Asian patients and 540 controls. All miRNAs were quantified using qRT-PCR assays. The pooled sensitivity was 82% (95%CI = 77–86%), pooled specificity was 76% (95%CI = 71–80%), and pooled DOR was 13.6 (95%CI = 8.8–21.8). The best biomarkers with high sensitivity were miR-16-2-3p (94%), miR-223-5p (91%), miR-130a-3p (90%), and miR182-5p (94%). Similarly, they showed high specificity, in addition to miR-34c-5p. Six panels of two to four exosomal miRNAs showed higher diagnostic values with an area under the curve (AUC) ranging from 0.906 to 0.981. The best discriminative ability to differentiate between cancer and non-cancer individuals was observed for miR-146b-5p + miR-223-5p + miR-182-5p (AUC = 0.981, sensitivity = 93.8% (84.9–98.3), specificity = 92.9% (76.5–99.1)). In conclusion, the expression levels of exosomal miRNAs could predict TC.