High diagnostic value of miRNAs for NSCLC: quantitative analysis for both single and combined miRNAs in lung cancer

MicroRNAs (miRNAs) are good candidates as biomarkers for Lung cancer (LC). The aim of this article is to figure out the diagnostic value of both single and combined miRNAs in LC. Normative meta-analysis was conducted based on PRISMA. We assessed the diagnostic value by calculating the combined sensitivity (Sen), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) and the area under the curve (AUC) of single and combined miRNAs for LC and specific subgroups. A total of 80 qualified studies with a total of 8971 patients and 10758 controls were included. In non-small cell lung carcinoma (NSCLC), we involved 20 single-miRNAs and found their Sen, Spe and AUC ranged from 0.52-0.81, 0.66-0.88, and 0.68-0.90, respectively, specially, miR-19 with the maximum Sen, miR-20 and miR-10 with the highest Spe as well as miR-17 with the maximum AUC. Additionally, we detected miR-21 with the maximum Sen of 0.74 [95%CI: 0.62-0.83], miR-146 with the maximum Spe and AUC of 0.93 [95%CI: 0.79-0.98] and 0.89 [95%CI: 0.86-0.92] for early-stage NSCLC. We also identified the diagnostic power of available panel (miR-210, miR-31 and miR-21) for NSCLC with satisfying Sen, Spe and AUC of 0.82 [95%CI: 0.78-0.84], 0.87 [95%CI: 0.84-0.89] and 0.91 [95%CI: 0.88-0.93], and furtherly constructed 2 models for better diagnosis. We identified several single miRNAs and combined groups with high diagnostic power for NSCLC through pooled quantitative analysis, which shows that specific miRNAs are good biomarker candidates for NSCLC and further researches needed.

微小RNA（MicroRNAs, miRNAs）是肺癌（Lung cancer, LC）极具潜力的生物标志物候选分子。本研究旨在明确单一miRNA及联合miRNA对肺癌的诊断价值。本研究遵循PRISMA规范开展规范性荟萃分析，通过计算单一及联合miRNA针对肺癌及特定亚组的合并灵敏度（Sensitivity, Sen）、特异度（Specificity, Spe）、阳性似然比（Positive Likelihood Ratio, PLR）、阴性似然比（Negative Likelihood Ratio, NLR）、诊断比值比（Diagnostic Odds Ratio, DOR）以及受试者工作特征曲线下面积（Area Under the Curve, AUC），评估其诊断效能。
最终纳入符合标准的研究共80项，涉及患者8971例、对照个体10758例。在非小细胞肺癌（Non-Small Cell Lung Carcinoma, NSCLC）亚组中，共纳入20种单一miRNA，其合并灵敏度、特异度及AUC分别介于0.52~0.81、0.66~0.88与0.68~0.90之间；其中miR-19的灵敏度最高，miR-20与miR-10的特异度最优，miR-17的AUC最大。
针对早期非小细胞肺癌，本研究检测发现miR-21的灵敏度最高，达0.74[95%置信区间（95%CI）：0.62~0.83]；miR-146的特异度与AUC均为最优，分别为0.93[95%CI：0.79~0.98]与0.89[95%CI：0.86~0.92]。此外，本研究还明确了由miR-210、miR-31与miR-21组成的miRNA联合检测组对非小细胞肺癌的诊断效能，其合并灵敏度、特异度及AUC分别为0.82[95%CI：0.78~0.84]、0.87[95%CI：0.84~0.89]与0.91[95%CI：0.88~0.93]，并进一步构建了2种优化诊断模型。
本研究通过合并定量分析，筛选出数种对非小细胞肺癌具有高诊断效能的单一miRNA及联合检测组，证实特定miRNA是非小细胞肺癌极具潜力的生物标志物候选分子，同时提示后续仍需开展进一步相关研究。