microRNA和ctDNA诊断上皮性卵巢癌间接比较的Meta分析

目的采用Meta分析和基于共同参考标准的间接比较方法评价microRNA和ctDNA在上皮性卵巢癌(EOC)诊断中的临床价值。方法计算机检索PubMed、EMbase、Medline、The Cochrane Library、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)、万方科技期刊全文数据库、维普中文科技期刊全文数据库(VIP),检索时限均从建库至2020年9月。由两名研究者根据事先制定的纳入及排除标准独立进行文献筛选并提取基本资料,依据诊断准确性研究的质量评估(QUADAS-2)工具评价文献质量。采用Meta-Disc 1.4软件和Stata 12.0软件进行Meta分析,计算合并敏感性、合并特异性、合并阳性似然比、合并阴性似然比、合并诊断优势比(DOR)。采用RevMan 5.3软件绘制汇总受试者工作特征曲线(SROC),采用敏感性分析评估结果的稳定性。采用Deek's漏斗图非对称检验评估是否存在发表偏倚。通过R软件实现microRNA和ctDNA间接比较的相对诊断比值比(RDOR)结果。结果最终纳入19篇文献,包含1351例EOC患者,1194例对照。异质性检验提示存在非阈值效应引起的明显异质性。采用随机效应模型对microRNA诊断EOC的研究进行Meta分析,结果显示,合并敏感性为0.74(95%CI:0.72~0.76),合并特异性为0.82(95%CI:0.80~0.84),合并阳性似然比为4.62(95%CI:3.35~6.38),合并阴性似然比为0.24(95%CI:0.17~0.35),合并DOR为21.62(95%CI:13.57~34.44),AUC为0.894。ctDNA诊断EOC的Meta分析结果显示,合并敏感性为0.76(95%CI:0.72~0.80),合并特异性为0.86(95%CI:0.83~0.89),合并阳性似然比为5.81(95%CI:3.60~9.38),合并阴性似然比为0.29(95%CI:0.21~0.41),合并DOR为22.61(95%CI:13.27~38.52),AUC为0.884。间接比较结果显示microRNA、ctDNA对EOC诊断的准确性之间差异无统计学意义。Deek's漏斗图非对称检验提示不存在明显发表偏倚。结论microRNA、ctDNA对EOC的临床诊断价值相当。

A Meta-analysis of indirect comparison between microRNA and ctDNA in the diagnosis of epithelial ovarian cancer

Objective To evaluate the clinical value of microRNA and ctDNA in the diagnosis of epithelial ovarian cancer(EOC)by Meta-analysis and indirect comparison based on common reference standard.Methods The PubMed,EMbase,Medline,The Cochrane Library,China biology medicine(CBM),China national knowledge infrastructure(CNKI),Wanfang database,Chinese Weipu database(VIP)were searched by computer from inception to September 2020.The literatures screening and data extraction were conducted independently by two reviewers according to the inclusion and exclusion criteria,and the literature quality was evaluated according to the second version of the quality assessment of diagnostic accuracy studies(QUADAS-2).Meta-analysis was performed with Meta-Disc 1.4 software and Stata 12.0 software to calculate the pooled sensitivity,pooled specificity,pooled positive likelihood ratio,pooled negative likelihood ratio and pooled diagnostic odds ratio(DOR).The summary receiver operating characteristic(SROC)curve was plotted by RevMan 5.3,and the stability of the results was evaluated by sensitivity analysis.The publication bias was evaluated by the asymmetry test of the Deek's funnel plot.The relative diagnostic odds ratio(RDOR)results of indirect comparison between microRNA and ctDNA were obtained by R software.Results A total of 19 literatures were included finally,including a total of 1351 EOC cases,and 1194 control cases.Heterogeneity test showed that there was significant heterogeneity caused by non-threshold effect.The Meta-analysis of the studies on microRNA diagnosis of EOC was conducted by random effect model,then the results showed that the pooled sensitivity,pooled specificity,pooled positive likelihood ratio,pooled negative likelihood ratio,pooled DOR and AUC were 0.74(95%CI 0.72-0.76),0.82(95%CI 0.80-0.84),4.62(95%CI 3.35-6.38),0.24(95%CI 0.17-0.35),21.62(95%CI 13.57-34.44)and 0.894 respectively.The Meta-analysis results of ctDNA in the diagnosis of EOC showed that the pooled sensitivity,pooled specificity,pooled positive likelihood ratio,pooled negative likelihood ratio,pooled DOR and AUC were 0.76(95%CI 0.72-0.80),0.86(95%CI 0.83-0.89),5.81(95%CI 3.60-9.38),0.29(95%CI 0.21-0.41),22.61(95%CI 13.27-38.52)and 0.884 respectively.The results of indirect comparison showed that there was no significant difference in the diagnostic accuracy of EOC between microRNA and ctDNA.The asymmetry test of Deek's funnel plot showed no significant publication bias.Conclusion MicroRNA and ctDNA have similar clinical diagnostic value for EOC.