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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

Flowchart for inclusion and exclusion of studies in the meta-analysis. HCC =  hepatocellular carcinoma.
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Figure 1: Flowchart for inclusion and exclusion of studies in the meta-analysis. HCC =  hepatocellular carcinoma.

Mentions: A total of 22 studies21–42 were included in the meta-analysis, with 2424 subjects in total, including 1280 patients with HCC. The 1144 patients without HCC were included in these studies as control groups, which comprised healthy volunteers, or chronic hepatitis (HBV-related or HCV-related) or cirrhosis patients. Most of these studies had presented a composite control population. The flowchart for the inclusion and exclusion of these studies is presented in Figure 1. Most of the subjects were from Asia, with the remaining patients from Italy,21 the United States,33 and Egypt.36 All the trials were prospective 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)

Flowchart for inclusion and exclusion of studies in the meta-analysis. HCC =  hepatocellular carcinoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Flowchart for inclusion and exclusion of studies in the meta-analysis. HCC =  hepatocellular carcinoma.
Mentions: A total of 22 studies21–42 were included in the meta-analysis, with 2424 subjects in total, including 1280 patients with HCC. The 1144 patients without HCC were included in these studies as control groups, which comprised healthy volunteers, or chronic hepatitis (HBV-related or HCV-related) or cirrhosis patients. Most of these studies had presented a composite control population. The flowchart for the inclusion and exclusion of these studies is presented in Figure 1. Most of the subjects were from Asia, with the remaining patients from Italy,21 the United States,33 and Egypt.36 All the trials were prospective 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