Review Article

Cell-free DNA as a Promising Diagnostic Biomarker in Prostate Cancer: A Systematic Review and Meta-Analysis

Table 1

Characteristics of the included studies.

CountryEthnicityCase (Age, N)Control (Age, N)Control typeTargetMethylationSpecimenAssay methodsCutoffSensitivitySpecificity

ChinaAsianN/A, 96N/A, 112Benign diseaseCfDNANoPlasmaqPCR (quantitative)0.86473.20%72.70%
ChinaAsianN/A, 96N/A, 112Benign diseaseCfDNANoPlasmaqPCR (quantitative)0.9181.70%78.80%
AmericanAmerican65.5, 8962.9, 163Benign diseaseGSTP1NoSerumqPCR (quantitative)180 ng/ml44.90%71.80%
AmericanAmerican65.5, 8563.1, 156Benign diseaseCfDNANoSerumqPCR (quantitative)180 ng/ml94.10%21.80%
AmericanAmerican65.5, 8563.1, 156Benign diseaseCfDNANoSerumPico green53.1 ng/ml94.10%15.40%
AmericanAmerican65.5, 8563.1, 156Benign diseaseCfDNANoSerumUv absorbanceN/A94.10%11.50%
BrazilAmerican66.81, 13366.40, 33Benign diseaseCfDNANoPlasmaPico green dsDNA quantification reagent kit140 ng/ml66.20%87.90%
AmericanAmerican64.9, 3464.5, 48Benign diseaseGADD45aYesSerumMs-SNuPE89.638.20%97.90%
AmericanAmerican64.9, 3464.5, 48Benign diseaseCfDNANoSerumqPCR (quantitative)18850.00%89.58%
ItalyEuropeanN/A, 29N/A, 25Benign diseaseCfDNANoUrine SupernatantqPCR (quantitative)0.04 ng/ul79.00%84.00%
ItalyEuropeanN/A, 55N/A, 55Benign diseaseCfDNANoUrine SupernatantqPCR (quantitative)0.04 ng/ul58.00%47.00%
ChinaAsianN/A, 98N/A, 47Benign diseaseCDH13promoterYesSerumMethylation-specific polymerase chain reaction (MSP)N/A44.90%100.00%
JapanAsian72.2, 7669.4, 20Benign diseaseHypermethylation APCYesSerumMethylation-specific polymerase chain reaction (MSP)0.00215.00%100.00%
JapanAsian72.2, 7669.4, 20Benign diseaseHypermethylation GSTP1YesSerumMethylation-specific polymerase chain reaction (MSP)0.14729.00%100.00%
JapanAsian72.2, 7669.4, 20Benign diseaseHypermethylation MDR1YesSerumMethylation-specific polymerase chain reaction (MSP)0.03746.00%100.00%
JapanAsian72.2, 7669.4, 20Benign diseaseHypermethylation RASSF1YesSerumMethylation-specific polymerase chain reaction (MSP)0.11924.00%100.00%
JapanAsian72.2, 7669.4, 20Benign diseaseHypermethylation PTGS2YesSerumMethylation-specific polymerase chain reaction (MSP)0.09112.00%100.00%
RomaniaEuropean68.0, 9164.0, 94Benign diseaseRARβ2YesSerumMethylation-specific polymerase chain reaction (MSP)N/A98.00%89.00%
RomaniaEuropean64.0, 3168.0, 44Benign diseaseGSTP1Yesplasmamethylation-specific polymerase chain reaction (MSP)N/A87.10%93.18%
AmericanAmerican59.0, 84N/A, 30ACMCAMYesSerumPyrosequencingN/A66.00%73.00%
AmericanAmerican59.0, 84N/A, 30ACMCAM/ERα/ErβYesSerumPyrosequencingN/A75.00%70.00%
DenmarkEuropeanN/A, 27N/A, 10BPHCCDC181/ST6GALNAC3/HAPLN3YesSerumqMSPN/A67.00%100.00%
DenmarkEuropeanN/A, 27N/A, 10BPHZNF660YesSerumddMSPN/A22.00%100.00%
PortugalEuropean71.0, 12157.0, 136ACFOXA1/RARβ2/RASSF1A/GSTP1YesPlasmaMultiplex qMSPN/A72.00%72.00%
PortugalEuropean71.0, 12157.0, 136ACFOXA1/RARβ2/RASSF1A)YesPlasmaMultiplex qMSPN/A64.00%70.00%
PortugalEuropean71.0, 12157.0, 136ACFOXA1YesPlasmaMultiplex qMSPN/A61.00%77.00%
PortugalEuropean71.0, 12157.0, 136ACGSTP1YesPlasmaMultiplex qMSPN/A15.00%98.00%
PortugalEuropean71.0, 12157.0, 136ACHOXD3YesPlasmaMultiple qMSPN/A80.00%43.00%
PortugalEuropean71.0, 12157.0, 136ACRARβ2YesPlasmaMultiplex qMSPN/A22.00%96.00%
PortugalEuropean71.0, 12157.0, 136ACRASSF1AYesPlasmaMultiplex qMSPN/A13.00%96.00%
PortugalEuropean71.0, 12157.0, 136ACSEP-19YesPlasmaMultiplex qMSPN/A12.00%99.00%
PortugalEuropean71.0, 12157.0, 136ACSOX17YesPlasmaMultiplex qMSPN/A29.00%93.00%

BPH, benign prostatic hyperplasia; AC, asymptomatic control; cfDNA, cell-free DNA; qMSP, quantitative methylation-specific PCR; ddMSP, methylation-specific droplet digital PCR; N/A, not available; N, number.