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. 2020 Apr 23;15(4):e0229593. doi: 10.1371/journal.pone.0229593

Table 4. Cox regression analysis of potential confounding variables conducted for the TCGA (N = 122), GSE6891 (N = 439), and meta-cohort (N = 561).

Cohorts were limited to samples with complete records for all explanatory variables investigated. Results are shown for the (A) univariate Cox regression analysis per explanatory variable and (B) associated multivariate Cox regression analyses limited to confounding variables tested significant in univariate Cox regression analyses. Table columns are as described in Table 3. Analyses were performed for overall survival.

A) Simple Cox Regression
TCGA cohort (N = 122) GSE6891 cohort (N = 439) AML meta-cohort (N = 561)
N Events HR 95% CI P N Events HR 95% CI P N Events HR 95% CI P
MAGS HSC 37 32 1 120 93 1 157 125 1
MEP 26 15 0.523 0.282–0.971 0.040* 108 56 0.491 0.352–0.685 2.75E-05*** 134 71 0.486 0.363–0.650 1.26E-06***
GMP 40 26 0.595 0.353–1.005 0.052 147 89 0.632 0.472–0.846 0.002** 187 115 0.622 0.483–0.802 2.50E-04***
UC 19 9 0.309 0.146–0.652 0.002** 64 40 0.666 0.460–0.965 0.032* 83 49 0.580 0.417–0.807 0.001**
Cytogenetic riska GOOD 24 10 1 97 40 1 NA NA NA NA NA
INTER 60 42 2.636 1.319–5.268 0.006** 247 160 1.900 1.341–2.690 3.02E-04*** NA NA NA NA NA
POOR 35 27 2.828 1.362–5.872 0.005** 85 69 3.222 2.173–4.778 5.84E-09*** NA NA NA NA NA
UC 3 3 8.159 2.188–30.431 0.002** 10 9 3.801 1.839–7.857 3.14E-04*** NA NA NA NA NA
FABb M0 13 9 1 16 13 1 29 22 1
M1 28 21 1.773 0.805–3.904 0.155 94 60 0.646 0.355–1.177 0.153 122 81 0.772 0.481–1.236 0.281
M2 27 17 1.156 0.520–2.659 0.697 104 64 0.629 0.346–1.142 0.128 131 81 0.698 0.435–1.119 0.135
M3 6 3 0.542 0.146–2.013 0.360 24 11 0.469 0.210–1.048 0.065 30 14 0.492 0.251–0.962 0.038*
M4 27 16 0.861 0.379–1.955 0.720 79 48 0.635 0.344–1.173 0.147 106 64 0.683 0.420–1.108 0.123
M4E NA NA NA NA NA 5 2 0.325 0.073–1.444 0.140 5 2 0.330 0.077–1.403 0.133
M5 14 10 1.957 0.785–4.879 0.150 103 72 0.780 0.432–1.407 0.408 117 82 0.846 0.528–1.356 0.488
M6 3 3 2.452 0.649–9.272 0.186 6 3 0.415 0.118–1.456 0.170 9 6 0.702 0.284–1.731 0.442
M7 3 3 2.311 0.615–8.679 0.215 0 0 NA NA NA 3 3 1.920 0.573–6.429 0.290
UC 1 0 2.751 NA 0.996 8 5 0.869 0.310–2.438 0.790 9 5 0.865 0.328–2.286 0.771
CEBPA NEG 119 80 1 406 262 1 525 342 1
POS 3 2 1.184 0.289–4.851 0.815 29 13 0.555 0.318–0.968 0.038* 32 15 0.556 0.332–0.933 0.026*
FLT3-ITD NEG 121 81 1 315 187 1 436 268 1
POS 1 1 5.724 0.766–42.766 0.089 124 91 1.665 1.294–2.141 7.18E-05*** 125 92 1.428 1.127–1.811 0.003**
FLT3-TKD NEG 107 71 1 390 254 1 497 325 1
POS 15 11 1.478 0.778–2.810 0.233 48 24 0.699 0.460–1.062 0.093 63 35 0.820 0.579–1.163 0.265
IDH1 NEG 116 78 1 405 256 1 521 334 1
POS 6 4 0.772 0.282–2.114 0.614 31 19 0.901 0.565–1.436 0.661 37 23 0.863 0.565–1.316 0.493
IDH2 NEG 113 78 1 400 254 1 513 332 1
POS 9 4 0.509 0.186–1.394 0.189 36 21 0.849 0.544–1.324 0.470 45 25 0.765 0.509–1.148 0.196
KRAS NEG 116 78 1 436 276 1 552 354 1
POS 6 4 0.669 0.244–1.836 0.435 3 2 1.028 0.256–4.132 0.970 9 6 1.031 0.460–2.311 0.941
NMP1 NEG 109 73 1 303 198 1 412 271 1
POS 13 9 1.739 0.864–3.501 0.121 136 80 0.874 0.674–1.133 0.310 149 89 0.845 0.665–1.074 0.169
NRAS NEG 115 77 1 396 253 1 511 330 1
POS 7 5 1.435 0.578–3.563 0.436 42 25 0.826 0.548–1.246 0.362 49 30 0.843 0.580–1.225 0.370
WBC WBC 122 82 1.002 0.998–1.006 0.402 NA NA NA NA NA NA NA NA NA NA
Age Age 122 82 1.041 1.022–1.060 1.44E-05*** 439 278 1.015 1.005–1.026 0.003** 561 360 1.025 1.017–1.033 2.64E-09***
Cohort TCGA NA NA NA NA NA NA NA NA NA NA 122 82 1
GSE6891 NA NA NA NA NA NA NA NA NA NA 439 278 0.579 0.451–0.744 1.99E-05***
B) Multivariate Cox Regression
TCGA cohort (N = 122) GSE6891 cohort (N = 439) AML meta-cohort (N = 561)
N Events HR 95% CI P N Events HR 95% CI P N Events HR 95% CI P
MAGS HSC 37 32 1 120 93 1 157 125 1
MEP 26 15 0.781 0.404–1.511 0.464 108 56 0.600 0.419–0.862 0.006** 134 71 0.524 0.374–0.734 1.69E-04***
GMP 40 26 0.780 0.445–1.365 0.383 147 89 0.723 0.537–0.973 0.032* 187 115 0.593 0.443–0.793 4.32E-04***
UC 19 9 0.467 0.213–1.025 0.058* 64 40 0.742 0.508–1.084 0.123 83 49 0.561 0.398–0.791 9.55E-04***
Cytogenetic riska GOOD 24 10 1 97 40 1 - - - - -
INTER 60 42 1.996 0.964–4.129 0.063 247 160 1.529 1.045–2.239 0.029 - - - - -
POOR 35 27 1.911 0.870–4.195 0.107 85 69 2.751 1.825–4.147 1.36E-06*** - - - - -
UC 3 3 7.440 1.928–28,712 0.004** 10 9 3.036 1.445–6.379 0.003** - - - - -
FABb M0 - - - - - - - - - - 29 22 1
M1 - - - - - - - - - - 122 81 1.267 0.769–2.087 0.353
M2 - - - - - - - - - - 131 81 1.266 0.766–2.094 0.358
M3 - - - - - - - - - - 30 14 1.089 0.531–2.233 0.816
M4 - - - - - - - - - - 106 64 1.143 0.684–1.911 0.610
M4E - - - - - - - - - - 5 2 0.861 0.196–3.790 0.844
M5 - - - - - - - - - - 117 82 1.595 0.934–2.723 0.087
M6 - - - - - - - - - - 9 6 1.140 0.418–3.112 0.798
M7 - - - - - - - - - - 3 3 2.006 0.573–7.021 0.276
UC - - - - - - - - - - 9 5 1.186 0.442–3.181 0.735
CEBPA NEG - - - - - 406 262 1 525 342 1
POS - - - - - 29 13 0.703 0.386–1.283 0.251 32 15 0.759 0.433–1.331 0.336
FLT3-ITD NEG - - - - - 315 187 1 436 268 1
POS - - - - - 124 91 1.621 1.230–2.135 6.04E-04*** 125 92 1.542 1.193–1.994 9.52E-04***
Age Age 122 82 1.035 1.017–1.054 1.71E-04*** 435 275 1.011 1.001–1.022 0.036* 557 357 1.021 1.012–1.030 4.56E-06***
Cohort TCGA NA NA NA NA NA NA NA NA NA NA 122 82 1
GSE6891 NA NA NA NA NA NA NA NA NA NA 439 278 0.640 0.472–0.869 0.005**

a Cytogenetic risk was excluded from Cox regression analyses conducted for the meta-cohort due to differences in cytogenetic risk group stratification between the TCGA (stratification based on cytogenetic and molecular genetics) and GSE6891 (stratification based on cytogenetic abnormalities only) cohorts.

b Samples recorded as FAB-Mx (N = 1), FAB-RAEB (N = 4), and FAB-RAEBt (N = 13) were removed.

Significance levels:

* ≤ 0.05;

** ≤0.01;

*** ≤ 0.001;

Abbreviations: N, total sample size; HR, hazards ratio; CI, confidence intervals; HSC, hematopoietic stem cells; MEP, megakaryocyte-erythroid progenitors; GMP, granulocytic- monocytic progenitors; UC, unclassified; INTER, intermediate