循环肿瘤DNA对结直肠癌KRAS基因突变检测诊断价值的Meta分析

Diagnostic value of circulating tumor DNA for determination of KRAS mutation in colorectal cancer:a meta-analysis

目的系统评价采用结直肠癌患者外周血循环肿瘤DNA(ctDNA)来检测KRAS基因突变状态的诊断价值.方法依据纳入和排除标准,检索PubMed、Embase、Cochrane图书馆3大数据库中有关采用结直肠癌患者外周血ctDNA检测KRAS基因突变状态的相关文献,采用诊断试验准确性质量评价工具(QUADAS-2)评价纳入文献的质量,应用Meta-DiSc 1.4及Stata 13.0等软件对纳入文献进行数据分析,并绘制森林图和SROC曲线,评估ctDNA的诊断价值.结果共检索文献1068篇,根据纳入及排除标准筛选出27篇文献,共31组数据.随机效应模型合并统计显示:外周血ctDNA检测KRAS基因突变状态的合并灵敏度、特异度、阳性似然比、阴性似然比、诊断比值比及SROC曲线下面积分别为0.61[95%CI:0.58~0.64]、0.94[95%CI:0.93~0.95]、10.10[95%CI:7.01~14.55]、0.38[95%CI:0.31~0.47]、34.79[95%CI:21.78~55.56]和0.92[95%CI:0.90~0.94].结论外周血ctDNA对结直肠癌KRAS基因突变状态检测的特异度较好,可用来实时监测基因状态的变化指导靶向治疗.

Objective To systematically evaluate the diagnostic value of peripheral blood circulating tumor DNA(ctDNA)for the determination of KRAS mutation in patients with colorectal cancer.Methods According to the inclusion and exclusion criteria,the relevant articles on the determination of KRAS mutation in peripheral blood ctDNA of patients with colorectal cancer were searched in three databases including PubMed,Embase and Cochrane Library.A Revised Tool for Quality Assessment on Diagnostic Accuracy Studies(QUADAS-2)was used to evaluate the quality of included articles.The data were analyzed by using software such as Meta-DiSc 1.4 and Stata 13.0.Forest plots and summary ROC(SROC)curve were used to assess the diagnostic value of ctDNA.Results A total of 1068 articles were searched,and 27 articles were included according to the inclusion and exclusion criteria,including 31 groups of data.The combined statistical analysis of random effect model showed that the combined sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,diagnostic odds ratio and area under the SROC curve of the KRAS gene mutation determined by peripheral blood ctDNA were 0.61[95%CI:0.58-0.64],0.94[95%CI:0.93-0.95],10.10[95%CI:7.01-14.55],0.38[95%CI:0.31-0.47],34.79[95%CI:21.78-55.56]and 0.92[95%CI:0.90-0.94],respectively.Conclusion Peripheral blood ctDNA shows a good specificity for the determination of KRAS gene mutation in colorectal cancer,and can be used to monitor the changes of gene status in real time to guide targeted therapy.