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Value of quantitative and qualitative analyses of circulating cell-free DNA as diagnostic tools for hepatocellular carcinoma: a meta-analysis.

Liao W, Mao Y, Ge P, Yang H, Xu H, Lu X, Sang X, Zhong S - Medicine (Baltimore) (2015)

Bottom Line: The results in this meta-analysis suggest that circulating cfDNA have potential value for HCC diagnosis.However, it would not be recommended for using independently, which is based on the nonrobust results.After combining with AFP, the diagnostic performance will be improved.

View Article: PubMed Central - PubMed

Affiliation: From the Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China.

ABSTRACT
Qualitative and quantitative analyses of circulating cell-free DNA (cfDNA) are potential methods for the detection of hepatocellular carcinoma (HCC). Many studies have evaluated these approaches, but the results have been variable. This meta-analysis is the first to synthesize these published results and evaluate the use of circulating cfDNA values for HCC diagnosis. All articles that met our inclusion criteria were assessed using QUADAS guidelines after the literature research. We also investigated 3 subgroups in this meta-analysis: qualitative analysis of abnormal concentrations of circulating cfDNA; qualitative analysis of single-gene methylation alterations; and multiple analyses combined with alpha-fetoprotein (AFP). Statistical analyses were performed using the software Stata 12.0. We synthesized these published results and calculated accuracy measures (pooled sensitivity and specificity, positive/negative likelihood ratios [PLRs/NLRs], diagnostic odds ratios [DORs], and corresponding 95% confidence intervals [95% CIs]). Data were pooled using bivariate generalized linear mixed model. Furthermore, summary receiver operating characteristic curves and area under the curve (AUC) were used to summarize overall test performance. Heterogeneity and publication bias were also examined. A total of 2424 subjects included 1280 HCC patients in 22 studies were recruited in this meta-analysis. Pooled sensitivity and specificity, PLR, NLR, DOR, AUC, and CIs of quantitative analysis were 0.741 (95% CI: 0.610-0.840), 0.851 (95% CI: 0.718-0.927), 4.970 (95% CI: 2.694-9.169), 0.304 (95% CI: 0.205-0.451), 16.347 (95% CI: 8.250-32.388), and 0.86 (95% CI: 0.83-0.89), respectively. For qualitative analysis, the values were 0.538 (95% CI: 0.401-0.669), 0.944 (95% CI: 0.889-0.972), 9.545 (95% CI: 5.298-17.196), 0.490 (95% CI: 0.372-0.646), 19.491 (95% CI: 10.458-36.329), and 0.87 (95% CI: 0.84-0.90), respectively. After combining with AFP assay, the values were 0.818 (95% CI: 0.676-0.906), 0.960 (95% CI: 0.873-0.988), 20.195 (95% CI: 5.973-68.282), 0.190 (95% CI: 0.100-0.359), 106.270 (95% CI: 22.317-506.055), and 0.96 (95% CI: 0.94-0.97), respectively. The results in this meta-analysis suggest that circulating cfDNA have potential value for HCC diagnosis. However, it would not be recommended for using independently, which is based on the nonrobust results. After combining with AFP, the diagnostic performance will be improved. Further investigation with more data is needed.

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SROC curves for qualitative, quantitative analysis and multiple analysis (combined with AFP assay). (A) SROC curves for the subgroup of quantitative analysis; (B) SROC curves for the subgroup of qualitative analysis; (C) SROC curves for multiple analysis (combined with α-fetoprotein (AFP) assay). The confidence ellipse indicates that the mean values for sensitivity and specificity were more likely to be in this region. The prediction ellipse (increased uncertainty) indicates that individual values for sensitivity and specificity were more likely to be in this region. AFP = α-fetoprotein, AUC = area under the curve, SROC = summary receiver operating characteristic.
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Figure 3: SROC curves for qualitative, quantitative analysis and multiple analysis (combined with AFP assay). (A) SROC curves for the subgroup of quantitative analysis; (B) SROC curves for the subgroup of qualitative analysis; (C) SROC curves for multiple analysis (combined with α-fetoprotein (AFP) assay). The confidence ellipse indicates that the mean values for sensitivity and specificity were more likely to be in this region. The prediction ellipse (increased uncertainty) indicates that individual values for sensitivity and specificity were more likely to be in this region. AFP = α-fetoprotein, AUC = area under the curve, SROC = summary receiver operating characteristic.

Mentions: Estimation of the SCOR curve is 1 method that can be used in meta-analysis to estimate overall diagnostic performance. It can demonstrate the trade-off between sensitivity and specificity values in multiple studies.14 In Figure 3, the observed data, together with the confidence and predictive ellipses, are presented in graphs of the SROC curves. In the quantitative analysis subgroup (Figure 3A), the AUC was 0.86 (95%CI: 0.83–0.89), which indicated a higher level of moderate overall accuracy.15 The LRT_I2 statistic value was 96.9 (95% CI: 94.70–99.09), indicating that an evident heterogeneity was present in these 7 studies. The LRT_Q (χ2) statistic was 64.42 (P = 0.000), indicating that the heterogeneity was likely the result of nonthreshold effects.


Value of quantitative and qualitative analyses of circulating cell-free DNA as diagnostic tools for hepatocellular carcinoma: a meta-analysis.

Liao W, Mao Y, Ge P, Yang H, Xu H, Lu X, Sang X, Zhong S - Medicine (Baltimore) (2015)

SROC curves for qualitative, quantitative analysis and multiple analysis (combined with AFP assay). (A) SROC curves for the subgroup of quantitative analysis; (B) SROC curves for the subgroup of qualitative analysis; (C) SROC curves for multiple analysis (combined with α-fetoprotein (AFP) assay). The confidence ellipse indicates that the mean values for sensitivity and specificity were more likely to be in this region. The prediction ellipse (increased uncertainty) indicates that individual values for sensitivity and specificity were more likely to be in this region. AFP = α-fetoprotein, AUC = area under the curve, SROC = summary receiver operating characteristic.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554041&req=5

Figure 3: SROC curves for qualitative, quantitative analysis and multiple analysis (combined with AFP assay). (A) SROC curves for the subgroup of quantitative analysis; (B) SROC curves for the subgroup of qualitative analysis; (C) SROC curves for multiple analysis (combined with α-fetoprotein (AFP) assay). The confidence ellipse indicates that the mean values for sensitivity and specificity were more likely to be in this region. The prediction ellipse (increased uncertainty) indicates that individual values for sensitivity and specificity were more likely to be in this region. AFP = α-fetoprotein, AUC = area under the curve, SROC = summary receiver operating characteristic.
Mentions: Estimation of the SCOR curve is 1 method that can be used in meta-analysis to estimate overall diagnostic performance. It can demonstrate the trade-off between sensitivity and specificity values in multiple studies.14 In Figure 3, the observed data, together with the confidence and predictive ellipses, are presented in graphs of the SROC curves. In the quantitative analysis subgroup (Figure 3A), the AUC was 0.86 (95%CI: 0.83–0.89), which indicated a higher level of moderate overall accuracy.15 The LRT_I2 statistic value was 96.9 (95% CI: 94.70–99.09), indicating that an evident heterogeneity was present in these 7 studies. The LRT_Q (χ2) statistic was 64.42 (P = 0.000), indicating that the heterogeneity was likely the result of nonthreshold effects.

Bottom Line: The results in this meta-analysis suggest that circulating cfDNA have potential value for HCC diagnosis.However, it would not be recommended for using independently, which is based on the nonrobust results.After combining with AFP, the diagnostic performance will be improved.

View Article: PubMed Central - PubMed

Affiliation: From the Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China.

ABSTRACT
Qualitative and quantitative analyses of circulating cell-free DNA (cfDNA) are potential methods for the detection of hepatocellular carcinoma (HCC). Many studies have evaluated these approaches, but the results have been variable. This meta-analysis is the first to synthesize these published results and evaluate the use of circulating cfDNA values for HCC diagnosis. All articles that met our inclusion criteria were assessed using QUADAS guidelines after the literature research. We also investigated 3 subgroups in this meta-analysis: qualitative analysis of abnormal concentrations of circulating cfDNA; qualitative analysis of single-gene methylation alterations; and multiple analyses combined with alpha-fetoprotein (AFP). Statistical analyses were performed using the software Stata 12.0. We synthesized these published results and calculated accuracy measures (pooled sensitivity and specificity, positive/negative likelihood ratios [PLRs/NLRs], diagnostic odds ratios [DORs], and corresponding 95% confidence intervals [95% CIs]). Data were pooled using bivariate generalized linear mixed model. Furthermore, summary receiver operating characteristic curves and area under the curve (AUC) were used to summarize overall test performance. Heterogeneity and publication bias were also examined. A total of 2424 subjects included 1280 HCC patients in 22 studies were recruited in this meta-analysis. Pooled sensitivity and specificity, PLR, NLR, DOR, AUC, and CIs of quantitative analysis were 0.741 (95% CI: 0.610-0.840), 0.851 (95% CI: 0.718-0.927), 4.970 (95% CI: 2.694-9.169), 0.304 (95% CI: 0.205-0.451), 16.347 (95% CI: 8.250-32.388), and 0.86 (95% CI: 0.83-0.89), respectively. For qualitative analysis, the values were 0.538 (95% CI: 0.401-0.669), 0.944 (95% CI: 0.889-0.972), 9.545 (95% CI: 5.298-17.196), 0.490 (95% CI: 0.372-0.646), 19.491 (95% CI: 10.458-36.329), and 0.87 (95% CI: 0.84-0.90), respectively. After combining with AFP assay, the values were 0.818 (95% CI: 0.676-0.906), 0.960 (95% CI: 0.873-0.988), 20.195 (95% CI: 5.973-68.282), 0.190 (95% CI: 0.100-0.359), 106.270 (95% CI: 22.317-506.055), and 0.96 (95% CI: 0.94-0.97), respectively. The results in this meta-analysis suggest that circulating cfDNA have potential value for HCC diagnosis. However, it would not be recommended for using independently, which is based on the nonrobust results. After combining with AFP, the diagnostic performance will be improved. Further investigation with more data is needed.

Show MeSH
Related in: MedlinePlus