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Table 4 Overall and stage-wise association of methylation panels in stool with risk of colorectal neoplasms

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

Gene panel First author, year, Ref. No. Country Study group No. DNAm assay OR (95% CI) p-valuea CRC stage N Stage-specific OR (95% CI) p-valuea p-valueb
MGMT, MLH1, and VIM (promoters) Baek, 2009 [44] South Korea NAA
AA
Ad
CRC
Cn
30
22
52
60
37
MSP 14.9 (4.4–50.8)
5.3 (1.5–18.8)
9.5 (3.2–28.2)
19.2 (6.3–58.2)
< 0.001
0.01
< 0.001
< 0.001
I/II
III/IV
35
25
16.0 (4.9–52.8)
25.6 (6.6–99.7)
< 0.001
< 0.001
0.450
ITGA4, SFRP2, and CDKN2A (promoters) Chang, 2010 [46] Korea NAA
AA
Ad
CRC
Cn
17
8
25
30
31
MSP 55.0 (5.9–509.9)
210.0 (11.7–3783.8)
77.1 (8.8–679.2)
70.0 (8.2–594.9)
< 0.001
< 0.001
< 0.001
< 0.001
I/II
III/IV
14
16
54.0 (5.6–524.0)
90.0 (9.1–889.9)
< 0.001
< 0.001
0.694d
SFRP2, GATA4/5, NDRG4, and VIM (promoters) Lu, 2014 [49] China CRC
Cn
56
40
MSP 50.1 (10.6–237.1) < 0.001 I/II
III/IV
32
24
27.9 (5.8–134.2)
89.6 (5.1–1583.0)c
< 0.001
< 0.001
0.501d
SFRP2 and WIF-1 (promoters) Zhang, 2014 [50] China NAA
AA
Ad
CRC
Cn
20
15
35
48
30
MSP 35.4 (4.0–313.4)
116.0 (10.9–1229.9)
55.6 (6.7–459.5)
125.7 (15.1–1048.2)
< 0.001
< 0.001
< 0.001
< 0.001
I/A
II/B
III/C
IV/D
7
20
14
7
174.0 (9.5–3187.4)
116.0 (11.9–1128.2)
72.5 (7.2–727.6)
295.0 (10.9–7994.2)c
< 0.001
< 0.001
< 0.001
< 0.001
0.605d
SFRP2, TFPI2, NDRG4, and BMP3 (promoters) Park, 2017 [34] South Korea AA
CRC
Cn
36
35
40
MSP 3.2 (1.2–8.3)
20.2 (4.3–95.7)
0.017
< 0.001
I/II
III/IV
17
18
9.2 (1.9–45.5)
45.0 (2.5–798.2)c
0.003
0.000
0.229d
COL4A2 and TLX2 (promoter/exon 1) Liu, 2019 [40] China AA
CRC
Cn
77
80
83
qMSP 43.8 (10.0–190.9)
422.4 (85.0–2098.2)
< 0.001
< 0.001
I/II
III/IV
43
37
249.8 (48.1–1296.4)
1458.0 (128.1–16,600.2)
< 0.001
< 0.001
0.168
  1. Note: Stages I/II/III/IV as per UICC classification and stages A/B/C/D as per Dukes classification
  2. Ref. reference, No. number, DNAm DNA methylation, MSP methylation-specific polymerase chain reaction, qMSP quantitative methylation-specific real-time 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. aStatistical significance for OR
  4. bStatistical significance for association between methylation level and CRC stage
  5. cCalculated using Haldane–Anscombe correction (0.5 added to each cell) [53, 54]
  6. dCalculated using Fisher’s exact test