| Objective:Quantitative and qualitative analysis of circulating tumor DNA(ct DNA)are potential methods for clinical diagnosis of epithelial ovarian cancer(EOC).At present,many studies have evaluated it.This study systematically evaluated the clinical value and accuracy of circulating tumor DNA in the diagnosis of epithelial ovarian cancer by meta-analysis.Methods:We searched Pub Med,Embase,Cochrane Library,Web of science,Clinical Trails.gov,Google Scholar,OVID,Elsevier Journals,Wiley Journals,CNKI,WANFANG DATA,and CJFD from building of these database to January 2019.We selected relevant clinical studies on the diagnosis of epithelial ovarian cancer using qualitative or quantitative analysis of ct DNA,and screened them according to the inclusive and exclusive criteria.The sensitivity and specificity data of ct DNA for EOC diagnosis were summarized.Meta-regression was performed to determine the heterogeneity of the source,and all analyses were performed using Review Manager5.3 and Stata 12.0 software.Results:According to the PRISMA statement for papers screening,a total of 14 studies were included.One of the papers adopted three different combinations of genes for ct DNA methylation analysis.Two papers adopted two different genes for quantitative analysis of ct DNA.So a total of 18 studies were enrolled,including 778 patients with epithelial ovarian cancer were included,and 1,019 patients in the control group.Estimates of circulating tumor DNA for the diagnosis of epithelial ovarian cancer were as follows: Sensitivity was 0.80,(95% CI: 0.74-0.85);specificity was 0.85,(95%CI: 0.79-0.89);The area under curve(AUC)of the systematic receiver operating curve(SROC)was 0.89,(95% CI: 0.85-0.91).The qualitative method of ct DNA methylation was used to diagnose epithelial ovarian cancer: Sen 0.87(95%CI:0.82-0.91);Spe 0.81,(95%CI: 0.70-0.89);The AUC of SROC curve was 0.89(95%CI:0.86-0.91).The ct DNA quantitative method wasused to diagnose EOC: Sen0.76(95%CI:0.68-0.82);Spe 0.87,(95%CI: 0.80-0.92);The AUC of SROC curve was 0.87(95%CI: 0.84-0.90).When we analysis of total sample size group(n≥100)compared with(n < 100)group,we found sensitivity of 0.82 versus 0.77,specificity of 0.85 versus 0.85,+LR of 5.57 versus 5.16,-LR of0.21 versus 0.27,DOR of 26.38 versus 19.33 and AUC of 0.90 versus 0.87.And analysis of serum sample group compared with plasma group,we found sensitivity of0.87 versus 0.74,specificity of 0.85 versus 0.85,+LR of 5.70 versus 5.03,-LR of 0.16 versus 0.30,DOR of 35.99 versus 16.58 and AUC of 0.90 versus 0.85.Conclusions:In the diagnosis of EOC,ct DNA has considerable sensitivity and specificity.The method of ct DNA methylation has higher sensitivity,and the method of ct DNA quantification has higher specificity.We found that studies on larger sample size groups(n≥100)had a higher overall accuracy ascompared with that of those on smaller sample size groups,and studies serum-based assays had a higher overall accuracy as compared with that of those on plasma-based assays.However,further large-scale prospective studies are needed to verify the potential applicability of ct DNA alone or in combination with conventional markers as diagnostic biomarkers for EOC,and to explore possible factors that influence the diagnostic accuracy of EOC. |
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