Table 1. Summary of studies included in the meta-analysis.
| First author | Year | QUADAS score | Patients | M/F | Sample | Assay method | Assay indicators | Cutoff | TP | FP | TN | FN | Sensitivity | Specificity | Youden index |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Aselmann et al. (14) | 2001 | 6 | 66 | NA | Blood | RT-PCR | Methylation (AFP) | 14 ng/mL | 6 | 5 | 39 | 16 | 13 | 89 | 0.02 |
| Bahnassy et al. (15) | 2014 | 6 | 183 | 121/12 | Blood | RT-PCR | Methylation (AFP) | 7.5 ng/mL | 115 | 5 | 57 | 6 | 96 | 91 | 0.87 |
| 2014 | 6 | 183 | 121/13 | Blood | RT-PCR | Methylation (CD133) | 73 ng/mL | 48 | 72 | 4 | 59 | 40 | 6 | 0.54 | |
| 2014 | 6 | 183 | 121/14 | Blood | RT-PCR | Methylation (CK19) | 49.8 ng/mL | 105 | 15 | 51 | 12 | 87 | 81 | 0.72 | |
| 2014 | 6 | 183 | 121/15 | Blood | RT-PCR | Methylation (CD90) | 400 ng/mL | 99 | 21 | 56 | 7 | 83 | 90 | 0.68 | |
| Chang et al. (16) | 2008 | 6 | 37 | NA | Plasma | MS-PCR | Methylation (APC) | N/A | 14 | 12 | 6 | 5 | 62 | 88 | 0.49 |
| 2008 | 6 | 37 | NA | Plasma | MS-PCR | Methylation (P16) | N/A | 15 | 9 | 4 | 9 | 79 | 50 | 0.20 | |
| 2008 | 6 | 37 | NA | Plasma | MS-PCR | Methylation (GSTP1) | N/A | 13 | 6 | 6 | 12 | 68 | 67 | 0.35 | |
| 2008 | 6 | 37 | NA | Plasma | MS-PCR | Methylation (RASSF1A) | N/A | 12 | 4 | 7 | 14 | 63 | 78 | 0.29 | |
| 2008 | 6 | 37 | NA | Plasma | MS-PCR | Methylation (Ecadherin) | N/A | 18 | 14 | 1 | 4 | 98 | 22 | 0.41 | |
| Chen et al. (17) | 2012 | 9 | 210 | 144/66 | Blood | qPCR | Methylation (cfDNA) | 213.8 ng/mL | 69 | 11 | 103 | 27 | 86 | 79 | 0.54 |
| Chen et al. (18) | 2013 | 8 | 84 | 68/17 | Serum | Chemiluminescense | Methylation (cfDNA) | N/A | 22 | 17 | 37 | 8 | 56 | 96 | 0.45 |
| 2013 | 8 | 84 | 68/18 | Serum | Chemiluminescense | Methylation (AFP) | N/A | 21 | 18 | 36 | 9 | 54 | 91 | 0.42 | |
| 2013 | 8 | 84 | 68/19 | Serum | Chemiluminescense | Methylation (AFU) | N/A | 26 | 13 | 29 | 16 | 67 | 76 | 0.52 | |
| 2013 | 8 | 84 | 68/20 | Serum | Chemiluminescense | Methylation (cfDNA + AFP) | N/A | 28 | 11 | 34 | 11 | 72 | 87 | 0.65 | |
| 2013 | 8 | 84 | 68/21 | Serum | Chemiluminescense | Methylation (CFDNA + AFU) | N/A | 34 | 5 | 28 | 17 | 87 | 71 | 0.59 | |
| 2013 | 8 | 84 | 68/22 | Serum | Chemiluminescense | Methylation (CFDAN + AFP + AFU) | N/A | 35 | 4 | 25 | 20 | 90 | 64 | 0.58 | |
| Chu et al. (19) | 2004 | 7 | 69 | 45/24 | Serum | MS-PCR | Methylation (P16) | N/A | 22 | 4 | 19 | 24 | 48 | 83 | 0.30 |
| Fu et al. (20) | 2017 | 7 | 1647 | NA | Blood | ELISA | Methylation (Hsp90a) | 62.44 ng/mL | 838 | 66 | 4 | 677 | 93 | 90 | 0.67 |
| 2017 | 7 | 1647 | NA | Blood | ELISA | Methylation (AFP20 | 6.98 ng/mL | 678 | 226 | 686 | 517 | 75 | 92 | 0.49 | |
| 2017 | 7 | 1647 | NA | Blood | ELISA | Methylation (HSP90a+AFP) | N/A | 847 | 57 | 701 | 686 | 94 | 94 | 0.39 | |
| Han et al. (21) | 2014 | 11 | 293 | 221/72 | Blood | MS-PCR | Methylation (AFP) | 20 ng/mL | 93 | 46 | 87 | 67 | 58 | 48 | 0.20 |
| 2014 | 11 | 293 | 221/73 | Blood | MS-PCR | Methylation (AFP) | 200 ng/mL | 49 | 7 | 126 | 111 | 31 | 92 | 0.06 | |
| 2014 | 11 | 293 | 221/74 | Blood | MS-PCR | Methylation (AFP) | 400 ng/mL | 39 | 1 | 132 | 121 | 24 | 99 | 0.23 | |
| 2014 | 11 | 293 | 221/75 | Blood | MS-PCR | Methylation (TRG5 + AFP) | 20 ng/mL | 130 | 54 | 79 | 30 | 81 | 39 | 0.23 | |
| 2014 | 11 | 293 | 221/76 | Blood | MS-PCR | Methylation (TRG5 + AFP) | 200 ng/mL | 109 | 19 | 114 | 51 | 68 | 78 | 0.47 | |
| 2014 | 11 | 293 | 221/77 | Blood | MS-PCR | Methylation (TRG5 + AFP) | 400 ng/mL | 104 | 13 | 120 | 56 | 65 | 85 | 0.50 | |
| Hosny et al. (22) | 2008 | 8 | 255 | NA | Tissue | PCR | Methylation (249ser P53) | NA | 1 | 168 | 11 | 75 | 1 | 94 | 0.28 |
| Huang et al. (23) | 2003 | 8 | 75 | 67/18 | Blood samples | RT PCR | Methylation (249ser P53) | 254 ng/mL | 10 | 6 | 44 | 15 | 40 | 88 | 0.80 |
| Huang et al. (24) | 2015 | 5 | 109 | NA | Serum | Pyrosequencing | Methylation (P16) | 5% | 49 | 8 | 35 | 17 | 65 | 87 | 0.38 |
| 2015 | 5 | 109 | NA | Serum | Pyrosequencing | Methylation (P16) | 7% | 33 | 2 | 41 | 33 | 39 | 97 | 0.53 | |
| 2015 | 5 | 109 | NA | Serum | Pyrosequencing | Methylation (P16) | 10% | 18 | 1 | 42 | 48 | 20 | 99 | 0.36 | |
| Huang et al. (25) | 2012 | 8 | 150 | 61/11 | Plasma | RQ-PCR | Quantitative analysis of CfDNA | 18 ng/mL | 65 | 7 | 71 | 7 | 90 | 90 | 0.19 |
| 2012 | 8 | 150 | 61/12 | Plasma | RQ-PCR | Quantitative analysis of CfDNA | 143 ng/mL | 43 | 29 | 49 | 29 | 60 | 78 | 0.07 | |
| Igetei et al. (26) | 2008 | 8 | 162 | NA | Plasma | Nested-PCR | Methylation (249ser P53) | N/A | 6 | 0 | 77 | 79 | 7 | 100 | 0.43 |
| Iizuka et al. (27) | 2006 | 9 | 82 | 65/35 | Serum | Real-time PCR | Quantitative analysis CfDNA | 73 ng | 36 | 16 | 14 | 16 | 69 | 93 | 0.63 |
| Iizuka et al. (28) | 2010 | 11 | 258 | 123/135 | Serum | MS-PCR | Methylation (SRD5A2) | NA | 4 | 144 | 2 | 108 | 4 | 99 | 0.50 |
| 2010 | 11 | 258 | 123/135 | Serum | MS-PCR | Methylation (SPINT2) | NA | 18 | 146 | 0 | 94 | 16 | 100 | 0.01 | |
| 2010 | 11 | 258 | 123/135 | Serum | MS-PCR | Methylation (AFP) | 20 ng/mL | 68 | 105 | 41 | 44 | 86 | 67 | 0.33 | |
| 2010 | 11 | 258 | 123/135 | Serum | MS-PCR | Methylation (PIVKA-2) | 40 mAU/ml | 59 | 138 | 8 | 53 | 89 | 70 | 0.50 | |
| Jeng et al. (29) | 2004 | 7 | 111 | 57/54 | Blood | RT-PCR | Methylation (AFP mRNA) | 1,000 ng/mL | 61 | 20 | 28 | 2 | 75 | 93 | 0.50 |
| Ji et al. (30) | 2014 | 9 | 289 | 100/21 | Serum | MS-PCR | Methylation (MT1G) | NA | 85 | 36 | 6 | 62 | 70 | 91 | 0.50 |
| Jiang et al. (31) | 2015 | 8 | 205 | NA | Serum/plasma | RT-PCR | Methylation (HBB) | 76 | 14 | 32 | 83 | 80 | 94 | 0.50 | |
| Julich-Haertel et al. (32) | 2017 | 8 | 517 | 310/145 | Serum/plasma | Fluorescence | Methylation (taMPs) | 9.3 | 63 | 23 | 355 | 76 | 73 | 82 | 0.50 |
| 2017 | 8 | 517 | 310/146 | Serum/plasma | Fluorescence | Methylation (taMPs) | 4.305 | 60 | 26 | 178 | 253 | 70 | 41 | 0.50 | |
| 2017 | 8 | 517 | 310/147 | Serum/plasma | Fluorescence | Methylation (taMPs) | 4.125 | 70 | 16 | 202 | 229 | 81 | 47 | 0.50 | |
| Kirk et al. (33) | 2000 | 8 | 119 | 97/22 | Blood | PCR | Methylation (249ser P53) | NA | 19 | 5 | 61 | 34 | 36 | 92 | 0.50 |
| Kuo et al. (34) | 2014 | 8 | 83 | NA | Plasma | MS-PCR | Methylation (HOXA9) | MI >0.88 | 23 | 14 | 42 | 7 | 73.3 | 97.1 | 0.50 |
| Mohamed et al. (35) | 2012 | 8 | 100 | 70/30 | Serum | Real-time PCR | Methylation (RASSF1A) | 640 nmol | 36 | 25 | 35 | 4 | 90 | 55 | 0.50 |
| Müller et al. (36) | 1997 | 8 | 91 | 12-Jul | Blood | PCR | Methylation (Albumin mRNA) | NA | 12 | 48 | 24 | 7 | 33 | 33 | 0.50 |
| Piciocchi et al. (37) | 2013 | 10 | 142 | 99/43 | Plasma | Real-time PCR | Quantitative analysis CfDNA | 1 ng | 40 | 31 | 45 | 26 | 91 | 43 | 0.50 |
| Ren et al. (38) | 2006 | 8 | 119 | NA | Plasma | Transilluminator | Quantitative analysis CfDNA | 36.6 ng | 41 | 38 | 9 | 31 | 52 | 95 | 0.50 |
| Schulze et al. (39) | 2013 | 7 | 78 | 60/18 | Blood | CellSearch | Methylation (EpCAM) | 18 | 1 | 18 | 41 | 56 | 92 | 0.50 | |
| Sun et al. (40) | 2013 | 10 | 93 | 36/7y | Serum | MS-PCR | Methylation (TFPI2) | NA | 20 | 9 | 41 | 23 | 47 | 82 | 0.50 |
| Tan et al. (41) | 2007 | 8 | 18 | NA | Serum | MS-PCR | Methylation (RUNX3) | NA | 7 | 1 | 0 | 10 | 88 | 100 | 0.50 |
| Witzigmann et al. (42) | 2002 | 5 | 201 | 118/92 | Blood | RT-PCR | Methylation (AFP mRNA) | 24 | 3 | 113 | 61 | 73 | 53 | 0.50 | |
| Wong et al. (43) | 2003 | 6 | 100 | NA | Serum/plasma | MS-PCR | Methylation (P16) | NA | 24 | 21 | 0 | 55 | 53 | 100 | 0.50 |
| Briefs et al. (44) | 1998 | 7 | 95 | NA | Serum/plasma | MS-PCR | Methylation (P16) | NA | 14 | 31 | 0 | 50 | 31 | 100 | 0.50 |
| Yang et al. (45) | 2005 | 6 | 130 | NA | Blood | RT-PCR | Methylation (AFPmRNA) | 35 | 3 | 62 | 30 | 54 | 95 | 0.50 | |
| Okajima (46) | 2017 | 8 | 110 | 79/31 | Plasma | RQ-PCR | Quantitative analysis CfDNA | 1.87×10 | 38 | 22 | 5 | 45 | 64 | 90 | 0.50 |
| Yeo et al. (47) | 2005 | 10 | 50 | 33/7y | Plasma | MS-PCR | Methylation (RASSF1A) | NA | 17 | 23 | 0 | 10 | 43 | 100 | 0.50 |
| Zhang et al. (48) | 2013 | 8 | 58 | 30/28 | Serum | Chip/Pyrosequencing | Methylation (DBX2) | NA | 28 | 3 | 3 | 24 | 88. 9 | 87 | 0.50 |
| Zhang et al. (49) | 2007 | 12 | 100 | 78/22 | Serum | MS-PCR | Methylation (P16) | NA | 22 | 28 | 2 | 48 | 44 | 96 | 0.50 |
| 2007 | 12 | 58 | 78/23 | Serum | Chip/Pyrosequencing | Methylation (THY1) | NA | 26 | 5 | 5 | 22 | 85 | 81 | 0.50 | |
| 2007 | 12 | 100 | 78/24 | Serum | MS-PCR | Methylation (P15) | NA | 11 | 39 | 0 | 50 | 22 | 100 | 0.50 | |
| 2007 | 12 | 100 | 78/25 | Serum | MS-PCR | Methylation (RASSF1A) | NA | 35 | 15 | 3 | 47 | 70 | 94 | 0.02 |
QUADAS, quality assessment of diagnostic accuracy studies; M/F, male/female; TP, true positive; FP, false positive; TN, true negative; FN, false negative.