Diagnostic and prognostic value of microRNAs in cholangiocarcinoma: a systematic review and meta-analysis

Background and aim: Several dysregulated microRNAs (miRNAs) have been implicated in the pathogenesis of cholangiocarcinoma (CCA); however, small sample sizes and invariable research designs are limitations, hindering a thorough analysis of miRNAs as diagnostic and prognostic tools for CCA. This study aimed to systematically summarize the clinical value of miRNAs in human CCA both for all available miRNAs and single miRNA with multiple researches. Methods: Pooled parameters included the area under the curve (AUC), sensitivity, specificity, and hazard ratios (HRs) to separately determine overall diagnostic and prognostic performance. Subgroup and sensitivity analyses were performed only in the event of heterogeneity. Thirty-four studies including 12 diagnostic studies and 22 prognostic studies were eligible for inclusion in this meta-analysis. Results: We observed that miR-21, miR-26, miR-483, miR-106a, miR-150, miR-192, and miR-194 were employed for distinguishing patients with CCA from healthy controls. Pooled sensitivity, specificity, and AUC were 0.82 (95% confidence interval [CI] 0.77-0.86), 0.83 (95% CI 0.75-0.89), and 0.88 (95% CI 0.85-0.91), respectively. Abnormal expression of miR-21, miR-26a, miR-192, miR-200c, miR-221, miR-29a, miR-191, miR-181c, miR-34a, miR-106a, miR-203, and miR-373 in patients was confirmed to associate with poor survival rate. Pooled HRs and 95% CIs were calculated using STATA, resulting in the pooled HR of 1.47 (95% CI 0.91-2.37) for overall survival (OS), 0.67 (95% CI 0.16-2.81) for disease-free survival (DFS), 2.31 (95% CI 1.59-3.36) for progression-free survival (PFS), and 2.68 (95% CI 0.88-8.15) for relapse-free survival (RFS). Thus, CCA patients with dysregulated miRNA expression were confirmed to have shorter OS, DFS, PFS, and RFS. Data regarding the diagnostic and prognostic roles of miR-21 suggested pooled diagnostic results of miR-21 for sensitivity, specificity, and AUC were 0.85 (95% CI 0.76-0.91), 0.92 (95% CI 0.81-0.97), and 0.93 (95% CI 0.91-0.95), respectively, suggesting better diagnostic performance of miR-21 compared with other miRNAs. Meanwhile, pooled prognostic result of miR-21 for HR was 1.88 (95% CI 1.41-2.51), indicating miR-21 could more appropriately predict shorter OS in patients with CCA. Conclusion: miRNAs may provide a new approach for clinical application, and miR-21 may be a promising biomarker for diagnosis and prognosis of CCA.