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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

Forest plots of estimates of sensitivity and specificity for the different subgroups. The point estimates (brown squares) and 95% CIs (error bars) for studies in different subgroups are presented in these Forest plots. (A and B) Forest plots for the quantitative analysis subgroup with the diagnostic indicator of abnormal concentration of total circulating cfDNA; (C and D) Forest plots for the qualitative analysis subgroup. This group of studies used tumor-specific single-gene methylation alterations as the evaluation indicator; (E and F) Forest plots for the multiple analysis subgroup (ie, combined with [AFP] assay). The sensitivity and specificity values in this group were re-estimated after adding AFP. AFP = α-fetoprotein, cfDNA = circulating cell-free DNA, CI = confidence interval.
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Figure 2: Forest plots of estimates of sensitivity and specificity for the different subgroups. The point estimates (brown squares) and 95% CIs (error bars) for studies in different subgroups are presented in these Forest plots. (A and B) Forest plots for the quantitative analysis subgroup with the diagnostic indicator of abnormal concentration of total circulating cfDNA; (C and D) Forest plots for the qualitative analysis subgroup. This group of studies used tumor-specific single-gene methylation alterations as the evaluation indicator; (E and F) Forest plots for the multiple analysis subgroup (ie, combined with [AFP] assay). The sensitivity and specificity values in this group were re-estimated after adding AFP. AFP = α-fetoprotein, cfDNA = circulating cell-free DNA, CI = confidence interval.

Mentions: However, when the AFP assay was added as a combined diagnostic indicator, all results improved—the values for pooled sensitivity and specificity were 0.818 (95% CI: 0.676–0.906) and 0.960 (95% CI: 0.873–0.988), respectively. PLR was 20.195 (95% CI: 5.973–68.282), NLR was 0.190 (95% CI: 0.100–0.359), and DOR was 106.270 (95% CI: 22.317–506.055). The results for the Forest plots are presented in Figure 2.


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)

Forest plots of estimates of sensitivity and specificity for the different subgroups. The point estimates (brown squares) and 95% CIs (error bars) for studies in different subgroups are presented in these Forest plots. (A and B) Forest plots for the quantitative analysis subgroup with the diagnostic indicator of abnormal concentration of total circulating cfDNA; (C and D) Forest plots for the qualitative analysis subgroup. This group of studies used tumor-specific single-gene methylation alterations as the evaluation indicator; (E and F) Forest plots for the multiple analysis subgroup (ie, combined with [AFP] assay). The sensitivity and specificity values in this group were re-estimated after adding AFP. AFP = α-fetoprotein, cfDNA = circulating cell-free DNA, CI = confidence interval.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Forest plots of estimates of sensitivity and specificity for the different subgroups. The point estimates (brown squares) and 95% CIs (error bars) for studies in different subgroups are presented in these Forest plots. (A and B) Forest plots for the quantitative analysis subgroup with the diagnostic indicator of abnormal concentration of total circulating cfDNA; (C and D) Forest plots for the qualitative analysis subgroup. This group of studies used tumor-specific single-gene methylation alterations as the evaluation indicator; (E and F) Forest plots for the multiple analysis subgroup (ie, combined with [AFP] assay). The sensitivity and specificity values in this group were re-estimated after adding AFP. AFP = α-fetoprotein, cfDNA = circulating cell-free DNA, CI = confidence interval.
Mentions: However, when the AFP assay was added as a combined diagnostic indicator, all results improved—the values for pooled sensitivity and specificity were 0.818 (95% CI: 0.676–0.906) and 0.960 (95% CI: 0.873–0.988), respectively. PLR was 20.195 (95% CI: 5.973–68.282), NLR was 0.190 (95% CI: 0.100–0.359), and DOR was 106.270 (95% CI: 22.317–506.055). The results for the Forest plots are presented in Figure 2.

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