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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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Related in: MedlinePlus

Funnel plots for the assessment of potential publication bias in the qualitative and quantitative analysis subgroups. (A) Funnel plots for the subgroup of quantitative analysis. (B) Funnel plots for the subgroup of qualitative analysis. The funnel graph indicates the results for the linear regression of the log odds ratios on the inverse root of the effective sample sizes. Each solid circle represents a study included in the meta-analysis. The line in the center indicates the summary DOR. (C) Funnel plots for the assessment of potential publication bias in the qualitative analysis subgroup using nonparametric “trim and fill” analysis. The funnel graph is a plot of the log of the DOR against the SE of the log of the DOR. “Theta” is the effect estimate and is the log DOR in this graph. DOR = diagnostic odds ratio, ESS = effective sample sizes.
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Figure 5: Funnel plots for the assessment of potential publication bias in the qualitative and quantitative analysis subgroups. (A) Funnel plots for the subgroup of quantitative analysis. (B) Funnel plots for the subgroup of qualitative analysis. The funnel graph indicates the results for the linear regression of the log odds ratios on the inverse root of the effective sample sizes. Each solid circle represents a study included in the meta-analysis. The line in the center indicates the summary DOR. (C) Funnel plots for the assessment of potential publication bias in the qualitative analysis subgroup using nonparametric “trim and fill” analysis. The funnel graph is a plot of the log of the DOR against the SE of the log of the DOR. “Theta” is the effect estimate and is the log DOR in this graph. DOR = diagnostic odds ratio, ESS = effective sample sizes.

Mentions: The Egger test, a linear regression of log odds ratios on the inverse root of the effective sample sizes, is used to test the funnel plot asymmetry in diagnostic meta-analyses.19 The funnel plot for the quantitative subgroup (Figure 5A) had a coefficient of 3.04 (95% CI: −84.96–91.05) and the P-value of 0.933, which indicated that the funnel plot was symmetric. Publication bias was not present in these studies.


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)

Funnel plots for the assessment of potential publication bias in the qualitative and quantitative analysis subgroups. (A) Funnel plots for the subgroup of quantitative analysis. (B) Funnel plots for the subgroup of qualitative analysis. The funnel graph indicates the results for the linear regression of the log odds ratios on the inverse root of the effective sample sizes. Each solid circle represents a study included in the meta-analysis. The line in the center indicates the summary DOR. (C) Funnel plots for the assessment of potential publication bias in the qualitative analysis subgroup using nonparametric “trim and fill” analysis. The funnel graph is a plot of the log of the DOR against the SE of the log of the DOR. “Theta” is the effect estimate and is the log DOR in this graph. DOR = diagnostic odds ratio, ESS = effective sample sizes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Funnel plots for the assessment of potential publication bias in the qualitative and quantitative analysis subgroups. (A) Funnel plots for the subgroup of quantitative analysis. (B) Funnel plots for the subgroup of qualitative analysis. The funnel graph indicates the results for the linear regression of the log odds ratios on the inverse root of the effective sample sizes. Each solid circle represents a study included in the meta-analysis. The line in the center indicates the summary DOR. (C) Funnel plots for the assessment of potential publication bias in the qualitative analysis subgroup using nonparametric “trim and fill” analysis. The funnel graph is a plot of the log of the DOR against the SE of the log of the DOR. “Theta” is the effect estimate and is the log DOR in this graph. DOR = diagnostic odds ratio, ESS = effective sample sizes.
Mentions: The Egger test, a linear regression of log odds ratios on the inverse root of the effective sample sizes, is used to test the funnel plot asymmetry in diagnostic meta-analyses.19 The funnel plot for the quantitative subgroup (Figure 5A) had a coefficient of 3.04 (95% CI: −84.96–91.05) and the P-value of 0.933, which indicated that the funnel plot was symmetric. Publication bias was not present in these studies.

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