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

Abstract

Background and aimSeveral 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.MethodsPooled 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.ResultsWe 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.ConclusionmiRNAs may provide a new approach for clinical application, and miR-21 may be a promising biomarker for diagnosis and prognosis of CCA.

Dihydromyricetin inhibits cell proliferation, migration, invasion and promotes apoptosis via regulating miR-21 in Human Cholangiocarcinoma Cells

“…Recently, a number of miRNAs including miR-424-5p [25] and miR-876 [26] have been reported to regulate cell proliferation, apoptosis, migration and invasion in CCA. MiR-21 is considered as a potential diagnostic and prognostic biomarker for CCA [8,9]. The plasma level of miR-21 is significantly upregulated in patients with CCA compared to healthy population [8] and CCA patients with elevated expression of miR-21 were related to poor survivals [9].…”

“…MicroRNA-21 (miR-21) is an oncogene in various types of human tumors. Recent studies indicate that miR-21 may be a potential diagnostic and prognostic biomarker for CCA [8,9]. As our previous study found that dihydromyricetin had great anti-atherosclerosis effects though regulating miR-21 [10], we were interested to investigate whether dihydromyricetin could exert anti-tumor effects in human CCA cell lines, and whether the underlying mechanism was through regulating miR-21.…”

“…Multiple studies have suggested that miR-21 plays an important role in the pathogenesis of CCA [9]. Increased expression of miR-21 was associated with poor overall survivals [8,9].…”

Systematic review and meta-analysis of cancer studies evaluating diagnostic test accuracy and prognostic values: approaches to improve clinical interpretation of results

“…The article, “Diagnostic and prognostic value of microRNAs in cholangiocarcinoma: a systematic review and meta-analysis”, published by Sun et al in the Cancer Management and Research journal, has caught our attention. 1 There are only few studies available on the subject of prognostic and diagnostic markers in cholangiocarcinoma, when compared with the literature available on other forms of cancer. For this reason, we believe that Sun et al’s study can be a valid reference point for future studies in this field.…”

“…Analysis of heterogeneity between diagnostic test accuracy studies: the study by Sun et al 1 has used the Chi-squared statistics to test against the null hypothesis and the I -squared statistics to study heterogeneity, but both these statistical values do not consider the threshold effect. It might be beneficial to also include the Tau-squared statistics as a part of the statistical analysis performed in this study.…”