Review Article

Quantitative and Qualitative Analysis of Circulating Cell-Free DNA Can Be Used as an Adjuvant Tool for Prostate Cancer Screening: A Meta-Analysis

Table 1

Characteristics and quality assessment of diagnostic clinical trials included in the meta-analysis.

Included studiesCountryCaseControlControl typeSample typeCutoffAssay methodsAssay indicatorsSensitivity (%) Specificity (%) Score
Mean ageMean age

Reis et al. (2015) [10]America3464.94864.5Benign patientSerum188 ng/mLqRT-PCRQuantitative analysis50.00%89.60%10

Wroclawski et al. (2013) [11]Brazil13366.83364.6Negative biopsiesPlasma140 ng/mLSAQuantitative analysis66.00%88.00%8

Feng et al. (2013) [12]China9663.211260.3BPHPlasma10 ng/mLqRT-PCRQuantitative analysis73.20%72.70%7

Ellinger et al. (2008) [13]Germany16865.84268.8BPHSerum19.7 ng/mL qRT-PCRQuantitative analysis87.50%64.00%9

Altimari et al. (2008) [14]Italy6464.545naHealthy volunteerPlasma8 ng/mLqRT-PCRQuantitative analysis80.00%82.00%9

Papadopoulou et al. (2004) [15]Greece12na13naHealthy volunteerPlasma10 ng/mLqRT-PCRQuantitative analysis58.00%92.00%7

Allen et al. (2004) [16]England15681067Healthy volunteerPlasma1000 GE/mLqRT-PCRQuantitative analysis85.00%73.00%8

Reis et al. (2015) [10]America3464.94864.5Benign patientSerum89.6Pyrosequencing (quantitative) Methylation (GADD45a) 38.20%97.90%10

Wang et al. (2014) [18]China98na47naBPH/bladder stone/healthy volunteerSerumnaMS-PCR (nonquantitative) Methylation (CDH13) 44.70%100.00%6

Okegawa et al. (2010) [19]Japan7672.22069.4Benign patientSerumnaMS-PCR (quantitative) Methylation (MDR1) 46.00%100.00%8
Methylation (GSTP1) 22.00%100.00%
Methylation (RASSF1A) 18.00%100.00%
Methylation (APC) 15.00%100.00%
Methylation (PTGS2) 12.00%100.00%

Sunami et al. (2009) [17] Canada8370.440naHealthy volunteerSerumnaMS-PCR (quantitative) Methylation (RASSF1) 24.00%100.00%10
Methylation (GSTP1) 13.00%100.00%
Methylation (RARB2) 12.00%100.00%

Ellinger et al. (2008) [32] Germany16865.84268.9BPHSerumnaqMS-PCR (quantitative) Methylation (GSTP1) 42.30%92.30%10
Methylation (TIG1) 9.50%100.00%
Methylation (PTGS2) 2.40%100.00%
Methylation (Reprimo) 1.20%100.00%

Rouprêt et al. (2008) [21] France22732262BPHBloodnaqMS-PCR (quantitative) Methylation (GSTP1) 91.00%91.00%11
Methylation (APC) 91.00%91.00%
Methylation (RARβ) 68.00%91.00%

Altimari et al. (2008) [14]Italy18na22naHealthy volunteerPlasmanaMS-PCR (nonquantitative) Methylation (GSTP1) 33.00%95.00%

Bryzgunova et al. (2008) [26]Russia5na5naHealthy volunteerPlasmanaBS (quantitative) Methylation (GSTP1) 100.00%100.00%

Bastian et al. (2008) [20]Germany19258.93560.1Negative biopsiesSerumnaqMS-PCR (quantitative) Methylation (MDR1) 32.00%100.00%10

Reibenwein et al. (2007) [27] Austria1470 (median) 49naHealthy volunteerSerumnaMS-PCR (nonquantitative) Methylation (GSTP1) 21.40%100.00%12
Methylation (AR) 40.30%73.50%

Chuang et al. (2007) [28]Taiwan36na27naBPHPlasmanaqMS-PCR (quantitative) Methylation (GSTP1) 31.00%93.00%8

Papadopoulou et al. (2004) [15]Greece12na9naHealthy volunteerPlasmanaMS-PCR (nonquantitative) Methylation (GSTP1) 75.00%100.00%7

Sunami et al. (2009) [17]America8560.24658.6Negative biopsiesSerumnaqMS-PCR (quantitative) Methylation (GSTP1) 12.00%100.00%10

Jerónimo et al. (2002) [29] America6963 (median) 3164 (median) BPHSerumnaMS-PCR (nonquantitative) Methylation (GSTP1) 36.00%100.00%9
qMSP (quantitative) Methylation (GSTP1) 13.00%100.00%

Goessl et al. (2001) [31]Germany33662664BPHPlasma/serumnaMS-PCR (nonquantitative) Methylation (GSTP1) 72.00%100.00%7

BPH = benign prostatic hyperplasia; MS-PCR = methylation-specific PCR; qMS-PCR = quantitative methylation-sensitive PCR; qMSP = quantitative methylation-specific PCR; SA = spectrophotometric assay; GE = genome equivalents, and BS = bisulphite sequencing.
19 patients under therapy were not included.
Methylation index.