Sun Chao, Zhu Jie, Wu Bin, Chen Jianlei, Zhu Zhenwei, Cai Peng, Guo Wanliang, Gu Zhicheng, Wang Jian, Huang Shungen
General Surgery Department, Children's Hospital of Soochow University, Suzhou, 215003, People's Republic of China,
Radiology Department, Children's Hospital of Soochow University, Suzhou, 215003, People's Republic of China.
Cancer Manag Res. 2018 Jul 18;10:2125-2139. doi: 10.2147/CMAR.S158155. eCollection 2018.
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.
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.
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.
miRNAs may provide a new approach for clinical application, and miR-21 may be a promising biomarker for diagnosis and prognosis of CCA.
多种失调的微小RNA（miRNA）与胆管癌（CCA）的发病机制有关；然而，样本量小和研究设计单一存在局限性，阻碍了对miRNA作为CCA诊断和预后工具的全面分析。本研究旨在系统总结miRNA在人类CCA中的临床价值，涵盖所有可用的miRNA以及多项研究中的单个miRNA。
汇总参数包括曲线下面积（AUC）、敏感性、特异性和风险比（HR），以分别确定总体诊断和预后性能。仅在存在异质性的情况下进行亚组分析和敏感性分析。34项研究，包括12项诊断性研究和22项预后性研究，符合纳入本荟萃分析的条件。
我们观察到miR-21、miR-26、miR-483、miR-106a、miR-150、miR-192和miR-194用于区分CCA患者与健康对照。汇总的敏感性、特异性和AUC分别为0.82（95%置信区间[CI]0.77 - 0.86）、0.83（95%CI 0.75 - 0.89）和0.88（95%CI 0.85 - 0.91）。患者中miR-21、miR-26a、miR-192、miR-200c、miR-221、miR-29a、miR-191、miR-181c、miR-34a、miR-106a、miR-203和miR-373的异常表达被证实与低生存率相关。使用STATA计算汇总的HR和95%CI，总生存（OS）的汇总HR为1.47（95%CI 0.91 - 2.37），无病生存（DFS）为0.67（95%CI 0.16 - 2.81），无进展生存（PFS）为2.31（95%CI 1.59 - 3.36），无复发生存（RFS）为2.68（95%CI 0.88 - 8.15）。因此，证实miRNA表达失调的CCA患者的OS、DFS、PFS和RFS较短。关于miR-21诊断和预后作用的数据表明，miR-21的汇总诊断结果的敏感性、特异性和AUC分别为0.85（95%CI 0.76 - 0.91）、0.92（95%CI 0.81 - 0.97）和0.93（95%CI 0.91 - 0.95），表明miR-21与其他miRNA相比具有更好的诊断性能。同时，miR-21的汇总预后结果的HR为1.88（95%CI 1.41 - 2.51），表明miR-21可以更恰当地预测CCA患者较短的OS。
miRNA可能为临床应用提供一种新方法，miR-21可能是CCA诊断和预后的有前景的生物标志物。
