Table 2 DNA methylation validation results
Publication | Gene/region tested | Methylation threshold | Mean methylation levels in healthy donors (n = 11) | Logrank test | Multivariate Cox analysisa of results significant in Kaplan–Meier analysis | ||
|---|---|---|---|---|---|---|---|
p-value for OS | p-value for EFS | p-value for OS | p-value for EFS | ||||
Lin et al. [13] | CEBPA distal promoter | 4.4%—Cutoff Finder [35] | 6% | 0.005b/0.3b | 0.05b/0.6c | 0.02b/- | 0.03b/- |
Hájková et al. [8] | CDKN2B, ESR1, MYOD1, CALCA, SOCS1, CDH1 | cumulative methylation valued ≥ 6 (median cumulative value) | CDKN2B—3%, ESR1—4%, MYOD1—5%, CALCA—16%, SOCS1—0.4%, CDH1—7% | 0.10f | 0.60f | – | – |
number of hypermethylated genese ≥ 4 (median number of hypermethylated genes) | 0.04f | 0.10f | 0.19 | – | |||
SOCS1 promoter | 1% (AML median) | 0.20f | 0.20f | – | – | ||
Treppendahl et al. [18] | VTRNA2-1 promoter | 10% | 38% | 0.90 | 0.50 | – | – |
38% | 0.70 | 0.40 | – | – | |||
Hájková et al. [10] | PBX3 (TAF1 binding site) | 27% (mean healthy donors) | 27% | 0.01 | 0.01 | 0.08 | 0.01 |
Jost et al. [11] | 1 CpG in DNMT3A promoter | 10% (AML mean) | 1% | 1/0.60g | 1/0.60g | – | – |
whole DMR | 1% | 0.80/0.905g | 0.80/0.70g | – | – | ||
Marcucci et al. [15] | CD34, RHOC, SCRN1, F2RL1, FAM92A1, MIR155HG, VWA8 | 10%/10.6%h (AML median of average methylation for all genes) | CD34—6%, RHOC—14%, SCRN1—6%, F2RL1—5%, FAM92A1—11%, MIR155HG—10%, VWA8—9% | 0.08/0.3h | 0.01/0.4h | – | 0.29/- |
13.7/16.95h (median of weighted summary scorei) | 0.02/0.2h | 0.01/0.7h | 0.8/- | 0.9/- | |||
≥ 6 genes have higher methylation than median in AML | 0.1/0.2h | 0.2/0.5h | – | – | |||
Božić et al. [21] | 1 CpG in C1R 5'UTR region | 19% (AML median) | 22% | 0.30 | 0.06 | – | – |
27% (AML median in the original study) | 0.30 | 0.1 | |||||
40%—Cutoff Finder [35] | 0.02 | 0.03 | 0.3 | 0.1 | |||
Zhou et al. [19] | GPX3 | 3.6% (mean of healthy donors + SD) | 2% | 0.04 | 0.01 | 0.006 | < 0.0001 |
Zhou et al. [20] | DLX4 | 8%—Cutoff Finder [35] | 11% | 0.02 | 0.02 | 0.03 | 0.03 |
Guo et al. [9] | SFRP1 promoter | 12% (AML mean)/10%—Cutoff Finder [35] | SFRP1—4% SFRP2—3% | 0.07/0.02 | 0.02/0.02 | -/0.21 | 0.06/0.06 |
SFRP2 promoter | 6% (AML mean)/5%—Cutoff Finder [35] | 0.3/0.3 | 0.5/0.8 | –/– | –/– | ||
SFRP1, SFRP2 | 9% (AML mean)/8.5%—Cutoff Finder [35] | 0.1/0.05 | 0.06/0.04 | -/0.44 | -/0.08 | ||
Li et al. [12] | NKD2 promoter | 6%—Cutoff Finder [35] | 3% | 0.5 | 0.2 | – | – |
11.5%—Cutoff Finder [35], CN-AML | 0.09 | 0.1 | – | – | |||
Liu et al. [14] | RASSF1A promoter | 0.4% (AML mean) | 1% | 0.4 | 0.4 | – | – |
Qu et al. [16] | LZTS2 | 37% (AML median) | LZTS2—57% NR6A1—16% | 0.02/0.01h | 0.008/0.02h | 0.05/0.01h | 0.0003/0.01h |
NR6A1 | 11% (AML median) | 0.001/0.002h | 0.001/0.004h | 0.004/0.0002h | 0.0003/0.0005h | ||
LTZS2, NR6A1 | methylation < median methylation level in both genes | 0.001/0.0001h | 0.001/0.0002h | 0.01/ < 0.0001h | < 0.0001/ < 0.0001h | ||
Šestáková et al. [17] | 2 CpGs in GZMB associated IGR | 45% (AML mean) at both/one/none of the two CpGs | 21% | 0.10 | 0.10 | – | – |