Table 3. . Hazard ratios and 95% confidence intervals for the associations between average methylation across CpG loci in specific genomic regions and overall survival, disease-specific survival and progression-free interval.
| Genomic region | N CpG loci | β-value, mean (SD) | Expression | Overall survival | Disease-specific survival | Progression-free interval | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Spearman's ρ | p-value | HR (95% CI)† | p-value | HR (95% CI)† | p-value | HR (95% CI)† | p-value | |||
| IL10 | ||||||||||
| Entire gene | 6 | 0.79 (0.07) | -0.479 | <0.001 | 0.94 (0.76, 1.17) | 0.577 | 0.88 (0.70, 1.12) | 0.298 | 0.91 (0.75, 1.12) | 0.368 |
| Weak transcription | 1 | 0.75 (0.09) | -0.254 | 0.001 | 0.70 (0.56, 0.89) | 0.003 | 0.68 (0.52, 0.88) | 0.003 | 0.80 (0.64, 1.00) | 0.050 |
| Quiescent/low | 5 | 0.79 (0.07) | -0.499 | <0.001 | 1.01 (0.82, 1.26) | 0.911 | 0.95 (0.75, 1.19) | 0.641 | 0.95 (0.77, 1.16) | 0.584 |
| TGFβ2 | ||||||||||
| Entire gene | 23 | 0.22 (0.03) | -0.321 | <0.001 | 0.99 (0.77, 1.28) | 0.960 | 1.06 (0.81, 1.39) | 0.660 | 1.18 (0.93, 1.50) | 0.180 |
| Active TSS | 8 | 0.05 (0.02) | -0.277 | <0.001 | 1.00 (0.80, 1.26) | 0.972 | 1.02 (0.79, 1.30) | 0.893 | 1.16 (0.94, 1.42) | 0.167 |
| Flanking active TSS | 8 | 0.07 (0.05) | -0.350 | <0.001 | 0.96 (0.74, 1.25) | 0.776 | 1.01 (0.77, 1.34) | 0.936 | 1.24 (0.99, 1.57) | 0.067 |
| Weak transcription | 5 | 0.61 (0.08) | -0.377 | <0.001 | 0.97 (0.78, 1.20) | 0.768 | 1.02 (0.81, 1.30) | 0.849 | 1.00 (0.82, 1.22) | 0.996 |
| Enhancers | 1 | 0.35 (0.13) | 0.132 | 0.094 | 1.11 (0.88, 1.39) | 0.383 | 1.14 (0.89, 1.47) | 0.307 | 1.15 (0.93, 1.43) | 0.197 |
| Quiescent/low | 1 | 0.72 (0.13) | 0.311 | <0.001 | 1.07 (0.84, 1.36) | 0.584 | 1.04 (0.80, 1.36) | 0.753 | 0.97 (0.77, 1.22) | 0.793 |
| IL8‡ | ||||||||||
| Entire gene | 2 | 0.48 (0.04) | 0.009 | 0.915 | 0.89 (0.69, 1.14) | 0.358 | 0.76 (0.57, 1.00) | 0.052 | 0.70 (0.54, 0.91) | 0.008 |
| TNF | ||||||||||
| Entire gene | 28 | 0.60 (0.07) | -0.443 | <0.001 | 1.14 (0.88, 1.48) | 0.318 | 1.19 (0.90, 1.59) | 0.225 | 1.04 (0.82, 1.32) | 0.756 |
| Weak transcription | 9 | 0.78 (0.07) | -0.390 | <0.001 | 1.43 (1.04, 1.97) | 0.026 | 1.56 (1.10, 2.21) | 0.013 | 1.08 (0.82, 1.43) | 0.580 |
| Quiescent/low | 19 | 0.52 (0.07) | -0.417 | <0.001 | 1.05 (0.82, 1.33) | 0.714 | 1.08 (0.82, 1.41) | 0.592 | 1.02 (0.81, 1.28) | 0.857 |
| IL6 | ||||||||||
| Entire gene | 11 | 0.43 (0.06) | -0.032 | 0.689 | 0.96 (0.77, 1.21) | 0.733 | 0.95 (0.74, 1.23) | 0.717 | 0.99 (0.80, 1.22) | 0.898 |
| Flanking active TSS | 4 | 0.39 (0.09) | -0.328 | <0.001 | 1.05 (0.82, 1.33) | 0.701 | 0.99 (0.75, 1.30) | 0.941 | 1.03 (0.82, 1.28) | 0.805 |
| Enhancers | 4 | 0.27 (0.05) | 0.191 | 0.015 | 0.91 (0.76, 1.10) | 0.339 | 0.93 (0.75, 1.16) | 0.537 | 0.96 (0.79, 1.15) | 0.644 |
| Weak repressed PolyComb | 1 | 0.50 (0.17) | 0.274 | <0.001 | 0.88 (0.72, 1.08) | 0.215 | 0.88 (0.70, 1.11) | 0.294 | 0.91 (0.75, 1.10) | 0.325 |
| Quiescent/low | 2 | 0.77 (0.08) | 0.049 | 0.540 | 1.14 (0.85, 1.53) | 0.387 | 1.21 (0.85, 1.70) | 0.290 | 1.14 (0.86, 1.52) | 0.372 |
| TGFβ3 | ||||||||||
| Entire gene | 16 | 0.39 (0.05) | -0.211 | 0.007 | 0.91 (0.72, 1.15) | 0.441 | 0.93 (0.72, 1.20) | 0.585 | 1.12 (0.90, 1.38) | 0.317 |
| Active TSS | 10 | 0.31 (0.04) | -0.160 | 0.043 | 0.98 (0.78, 1.24) | 0.879 | 1.00 (0.77, 1.28) | 0.970 | 1.17 (0.94, 1.46) | 0.169 |
| Flanking active TSS | 5 | 0.47 (0.08) | -0.221 | 0.005 | 0.86 (0.69, 1.09) | 0.220 | 0.88 (0.67, 1.15) | 0.342 | 1.05 (0.84, 1.30) | 0.676 |
| Strong transcription | 1 | 0.81 (0.03) | -0.264 | 0.001 | 0.88 (0.72, 1.09) | 0.244 | 0.87 (0.69, 1.09) | 0.211 | 1.01 (0.80, 1.26) | 0.955 |
| TGFβ1 | ||||||||||
| Entire gene | 25 | 0.32 (0.02) | 0.336 | <0.001 | 1.20 (0.94, 1.52) | 0.142 | 1.27 (0.96, 1.67) | 0.090 | 1.09 (0.86, 1.38) | 0.478 |
| Active TSS | 1 | 0.08 (0.04) | 0.105 | 0.184 | 0.98 (0.71, 1.36) | 0.915 | 0.94 (0.67, 1.33) | 0.741 | 0.83 (0.60, 1.15) | 0.260 |
| Flanking active TSS | 14 | 0.04 (0.01) | -0.384 | <0.001 | 1.11 (0.86, 1.45) | 0.418 | 1.15 (0.86, 1.54) | 0.351 | 0.99 (0.74, 1.32) | 0.945 |
| Weak transcription | 7 | 0.70 (0.06) | 0.480 | <0.001 | 1.17 (0.93, 1.48) | 0.174 | 1.26 (0.96, 1.65) | 0.096 | 1.11 (0.88, 1.41) | 0.379 |
| Enhancers | 3 | 0.78 (0.03) | -0.161 | 0.042 | 0.96 (0.77, 1.20) | 0.720 | 0.91 (0.71, 1.16) | 0.445 | 0.99 (0.79, 1.23) | 0.922 |
†
Fully adjusted models adjusted for age, sex, race, stage and six surrogate variables.
‡
Both CpG loci for IL8 were associated with the Quiescent/Low chromatin state.
Models were run using complete case analysis. Maximum sample sizes were 181 for overall survival, 174 for disease-specific survival and 181 for progression-free interval.
TSS: Transcription start site.