Skip to main content

Table 3 Overall and stage-wise diagnostic performance of individual DNA methylation markers in stool for detection of colorectal neoplasms

From: Fecal DNA methylation markers for detecting stages of colorectal cancer and its precursors: a systematic review

Gene First author, year, Ref. No. Country Study group No. DNAm assay Sn (%) AUC (95%CI), p-value CRC stage No. Stage-specific Sn (%) Specificity (%)
CDKN2A (promoter) Abbaszadegan, 2007 [42] Iran CRC
Cn
25
20
MSP 20   II/B
III/C
14
5
7
60
100
COL4A1 (promoter/exon 1) Liu, 2019 [40] China AA
CRC
Cn
77
80
83
qMSP 58
89
0.76 (0.69–0.84)
0.97 (0.94–0.99)
I/II
III/IV
43
37
88
89
88
COL4A2 (promoter/exon 1) Liu, 2019 [40] China AA
CRC
Cn
77
80
83
qMSP 49
93
0.78 (0.70–0.85)
0.97 (0.94–0.99)
I/II
III/IV
43
37
91
95
92
FBN1 (promoter) Guo, 2013 [25] China CRC
Cn
75
30
MSP 72   I
II
III
IV
12
30
30
3
92
63
73
67
93
FBN1 (promoter) Li, 2015 [27] China CRC
Cn
89
30
MSP 71*   I/A
II/B
III/C
17
36
36
77*
69*
94*
93
GATA4 (promoter) Hellebrekers, 2009 [37] Netherlands CRC
Cn
28
45
qMSP 71 0.81 (0.70–0.89) I/II
III/IV
18
10
55
100
84
CRC
Cn
47
30
qMSP 51   I/II
III/IV
29
17
48
59
93
GATA4 (promoter) Lu, 2014 [49] China CRC
Cn
56
40
MSP 43   I/II
III/IV
32
24
38
50
95
GATA5 (promoter) Lu, 2014 [49] China CRC
Cn
56
40
MSP 84   I/II
III/IV
32
24
78
92
83
HIC1 (promoter) Lenhard, 2005 Germany AA
CRC
Cn
13
26
50
MSP 31
42
  I/II
III/IV
6
20
67
25
98
ING1 (promoter) He, 2014 [26] China AA
CRC
Cn
27
61
20
n-MSP 63
74
  A/B
C/D
33
28
70
79
95
ITGA4 (promoter/exon 1) Liu, 2019 [40] China AA
CRC
Cn
77
80
83
qMSP 42
83
0.74 (0.66–0.81)
0.95 (0.92–0.99)
I/II
III/IV
43
37
81
84
96
miR-34a (promoter) Wu, 2014 [36] China CRC
Cn
82
40
MSP 77   I 13 62 95
miR-34b/c (promoter) Wu, 2014 [36] China CRC
Cn
82
40
MSP 94   I 13 85 100
miR-34b/c (promoter) Kalimutho, 2011 [33] Italy 0/ AA
CRC
Cn
5
23
39
MSP 60
78
  I
II
III
2
6
3
100
50
67
87
NDRG4 (promoter) Xiao , 2015 [32] China CRC
Cn
84
16
n-MSP 76   I/II
III/IV
48
36
81
69
89
NDRG4 (promoter) Lu, 2014 [49] China CRC
Cn
56
40
MSP 29   I/II
III/IV
32
24
22
38
98
OSMR (promoter) Kim, 2009 [24] Belgium CRC
Cn
69
81
qMSP 38   I
II
III
IV
18
27
18
6
11
56
44
17
95
RASSF2: Region 1 (promoter) Nagasaka, 2009 [45] Japan NAA
AA
Ad
CRC
Cn
29
27
56
84
113
Hi-SA
(n-MSP)
0
19
9
27
  I/II
III/IV
40
44
25
30
97
RASSF2: Region 2 (promoter) Nagasaka, 2009 [45] Japan NAA
AA
Ad
CRC
Cn
29
27
56
84
113
Hi-SA
(n-MSP)
4
7
5
36
  I/II
III/IV
40
44
23
48
97
SDC2 Niu, 2017 [51] China AA
CRC
Cn
122
196
179
qMSP 58
81
0.79 (0.74–0.85)
0.92 (0.89–0.95)
I/II
III/IV
87
109
84
79
93
SDC2 Han, 2019 [28] South Korea NAA
0/ AA
Ad
CRC
Cn
41
6
47
242
245
LTE-qMSP 24
83
32
90
0.90 (0.88–0.93)# I
II
III
IV
55
70
96
21
86
91
90
100
90
SDC2 Oh, 2017 [35] South Korea NAA
CRC
Cn
21
50
22
LTE-qMSP 33
90
0.93 (0.85–0.98) I
II
III
IV
12
17
10
11
83
88
90
100
91
SFRP2 (promoter) Kriegshäuser, 2017 [38] Austria CRC
Cn
18
22
MSRH 61   I
II
2
16
100
56
86
SFRP2 (promoter) Zhang, 2014 [50] China NAA
AA
Ad
CRC
Cn
20
15
35
48
30
MSP 55
80
66
56
  I/A
II/B
III/C
IV/D
7
20
14
7
71
50
57
57
100
SFRP2 (promoter) Lu, 2014 [49] China CRC
Cn
56
40
MSP 57   I/II
III/IV
32
24
50
67
90
SFRP2 (promoter) Tang, 2011 [47] China AA
CRC
Cn
63
169
30
MSP 46
84
  I/II
III/IV
99
70
83
86
93
SFRP2: Region 1 (promoter) Nagasaka, 2009 [45] Japan NAA
AA
Ad
CRC
Cn
29
27
56
84
113
Hi-SA
(n-MSP)
14
30
21
57
  I/II
III/IV
40
44
58
57
97
SFRP2: Region 2 (promoter) Nagasaka, 2009 [45] Japan NAA
AA
Ad
CRC
Cn
29
27
56
84
113
Hi-SA
(n-MSP)
14
22
18
38
  I/II
III/IV
40
44
38
39
96
SFRP2 (promoter) Wang, 2008 [43] China AA
CRC
Cn
34
69
30
qMSP
(Methy-Light)
62
87
  I/II
III/IV
30
39
83
90
93
SNCA (promoter) Yang, 2017 [52] China NAA
AA
Ad
CRC
Cn
36
13
49
31
64
qMSP 72
77
76
84
0.77, < 0.001
0.84, < 0.001
I/II
III/IV
17
13
82
85
75
SNCA (promoter) Li, 2015 [27] China CRC
Cn
89
30
MSP 70*   I/A
II/B
III/C
17
36
36
65*
81*
67*
100
SPART (promoter) Zhang, 2013 [48] China CRC
Cn
96
30
MSP 80   I 21 71 100
TLX2 (promoter/exon 1) Liu, 2019 [40] China AA
CRC
Cn
77
80
83
qMSP 55
89
0.79 (0.71–0.86)
0.96 (0.92–0.99)
I/II
III/IV
43
37
81
97
96
VIM (promoter) Lu, 2014 [49] China CRC
Cn
56
40
MSP 41   I/II
III/IV
32
24
41
42
85
VIM (promoter) Itzkowitz, 2008 [39] USA CRC
Cn
42
241
MSP 81   I
II
III
IV
11
14
14
3
91
86
64
100
82
VIM (exon 1) Chen, 2005 [41] USA CRC
Cn
94
198
MSP 46   I/II
III/IV
60
34
43
50
90
WIF-1 (promoter) Zhang, 2014 [50] China NAA
AA
Ad
CRC
Cn
20
15
35
48
30
MSP 35
53
46
60
  I/A
II/B
III/C
IV/D
7
20
14
7
57
70
50
57
97
  1. Notes: Stages I/II/III/IV as per UICC classification and stages A/B/C/D as per Dukes classification. Bold fonts represent results from validation set (non-bold fonts represent results without validation)
  2. Ref. reference, No. number, DNAm DNA methylation, MSP methylation-specific polymerase chain reaction, qMSP quantitative methylation-specific polymerase chain reaction, n-MSP nested methylation-specific polymerase chain reaction, Hi-SA high-sensitivity assay for bisulfite DNA, LTE linear target enrichment, MSRH methylation-specific reverse hybridization, NAA non-advanced adenoma, AA advanced adenoma, Ad adenoma, Cn control
  3. *The sum of methylation + stool samples divided by stages is not equal to the total number of methylation + CRC stool samples
  4. #For a combined group including three AA (stage 0 CRC) cases along with CRC cases