This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.
Testing the association between 17380 genes and 9 clinical features across 263 samples, statistically thresholded by Q value < 0.05, 8 clinical features related to at least one genes.
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334 genes correlated to 'Time to Death'.
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PPP3CB , RPRD2 , RIOK3 , ARHGEF12 , PTK2B , ...
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16 genes correlated to 'AGE'.
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ELOVL2 , MRPS33 , UNC80 , DOK6 , TSPYL5 , ...
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86 genes correlated to 'GENDER'.
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UTP14C , KIF4B , CCDC146 , CAV2 , UQCRH , ...
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621 genes correlated to 'PATHOLOGY.T'.
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KDR , DBX2 , ACTA1 , OPRK1 , NR5A1 , ...
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8 genes correlated to 'PATHOLOGY.N'.
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CARD16 , CASP1 , SFXN5 , LOC339535 , VGF , ...
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46 genes correlated to 'PATHOLOGICSPREAD(M)'.
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CMTM8 , C20ORF112 , OPRK1 , HTR6 , PLCD1 , ...
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648 genes correlated to 'TUMOR.STAGE'.
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KDR , ACTA1 , OPRK1 , DBX2 , FAM38B , ...
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130 genes correlated to 'NEOADJUVANT.THERAPY'.
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ALDOB , NKIRAS2 , PLXNB2 , MREG , UQCRH , ...
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No genes correlated to 'KARNOFSKY.PERFORMANCE.SCORE'
Complete statistical result table is provided in Supplement Table 1
Clinical feature | Statistical test | Significant genes | Associated with | Associated with | ||
---|---|---|---|---|---|---|
Time to Death | Cox regression test | N=334 | shorter survival | N=203 | longer survival | N=131 |
AGE | Spearman correlation test | N=16 | older | N=14 | younger | N=2 |
GENDER | t test | N=86 | male | N=8 | female | N=78 |
KARNOFSKY PERFORMANCE SCORE | Spearman correlation test | N=0 | ||||
PATHOLOGY T | Spearman correlation test | N=621 | higher pT | N=314 | lower pT | N=307 |
PATHOLOGY N | t test | N=8 | n1 | N=1 | n0 | N=7 |
PATHOLOGICSPREAD(M) | t test | N=46 | m1 | N=43 | m0 | N=3 |
TUMOR STAGE | Spearman correlation test | N=648 | higher stage | N=418 | lower stage | N=230 |
NEOADJUVANT THERAPY | t test | N=130 | yes | N=51 | no | N=79 |
Time to Death | Duration (Months) | 0.1-109.9 (median=28.3) |
censored | N = 169 | |
death | N = 91 | |
Significant markers | N = 334 | |
associated with shorter survival | 203 | |
associated with longer survival | 131 |
HazardRatio | Wald_P | Q | C_index | |
---|---|---|---|---|
PPP3CB | 0 | 2.657e-11 | 4.6e-07 | 0.332 |
RPRD2 | 50 | 7.839e-11 | 1.4e-06 | 0.676 |
RIOK3 | 6001 | 1.019e-10 | 1.8e-06 | 0.661 |
ARHGEF12 | 38 | 2.288e-10 | 4e-06 | 0.64 |
PTK2B | 0 | 3.038e-10 | 5.3e-06 | 0.327 |
IGLL1 | 0.01 | 4.758e-10 | 8.3e-06 | 0.315 |
MBNL2 | 26 | 5.475e-10 | 9.5e-06 | 0.666 |
EVI2A | 0.04 | 5.908e-10 | 1e-05 | 0.352 |
CCL26 | 0.07 | 6e-10 | 1e-05 | 0.358 |
SALL1 | 10.1 | 9.264e-10 | 1.6e-05 | 0.601 |
AGE | Mean (SD) | 61.45 (12) |
Significant markers | N = 16 | |
pos. correlated | 14 | |
neg. correlated | 2 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
ELOVL2 | 0.4639 | 1.942e-15 | 3.38e-11 |
MRPS33 | 0.3348 | 2.626e-08 | 0.000456 |
UNC80 | 0.3241 | 7.597e-08 | 0.00132 |
DOK6 | 0.3232 | 8.284e-08 | 0.00144 |
TSPYL5 | 0.3108 | 2.681e-07 | 0.00466 |
RANBP17 | 0.3102 | 2.837e-07 | 0.00493 |
ZYG11A | 0.3056 | 4.319e-07 | 0.0075 |
C7ORF13 | 0.3039 | 5.048e-07 | 0.00877 |
RNF32 | 0.3039 | 5.048e-07 | 0.00877 |
PVT1 | -0.3001 | 7.108e-07 | 0.0123 |
GENDER | Labels | N |
FEMALE | 89 | |
MALE | 174 | |
Significant markers | N = 86 | |
Higher in MALE | 8 | |
Higher in FEMALE | 78 |
T(pos if higher in 'MALE') | ttestP | Q | AUC | |
---|---|---|---|---|
UTP14C | 17.16 | 3.173e-32 | 5.52e-28 | 0.9707 |
KIF4B | -11.32 | 3.408e-23 | 5.92e-19 | 0.875 |
CCDC146 | -10.37 | 3.088e-21 | 5.37e-17 | 0.8014 |
CAV2 | -9.9 | 2.448e-19 | 4.25e-15 | 0.8063 |
UQCRH | 9.84 | 6.178e-19 | 1.07e-14 | 0.7634 |
DNAJB13 | -9.53 | 1.652e-18 | 2.87e-14 | 0.7841 |
SNORA48 | -9.2 | 1.193e-16 | 2.07e-12 | 0.8144 |
TLE1 | -9.1 | 3.69e-16 | 6.41e-12 | 0.8029 |
RERG | -8.38 | 7.736e-15 | 1.34e-10 | 0.7701 |
ADAMTS10 | -8.1 | 2.187e-14 | 3.8e-10 | 0.733 |
No gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.
KARNOFSKY.PERFORMANCE.SCORE | Mean (SD) | 92.92 (8.6) |
Score | N | |
70 | 1 | |
80 | 3 | |
90 | 8 | |
100 | 12 | |
Significant markers | N = 0 |
PATHOLOGY.T | Mean (SD) | 1.99 (0.99) |
N | ||
T1 | 121 | |
T2 | 32 | |
T3 | 102 | |
T4 | 8 | |
Significant markers | N = 621 | |
pos. correlated | 314 | |
neg. correlated | 307 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
KDR | 0.4995 | 5.251e-18 | 9.13e-14 |
DBX2 | 0.4605 | 3.275e-15 | 5.69e-11 |
ACTA1 | 0.456 | 6.593e-15 | 1.15e-10 |
OPRK1 | 0.452 | 1.196e-14 | 2.08e-10 |
NR5A1 | 0.436 | 1.251e-13 | 2.17e-09 |
SLC35F1 | 0.4346 | 1.528e-13 | 2.66e-09 |
AVPR1A | 0.4299 | 2.97e-13 | 5.16e-09 |
RRM2 | -0.4298 | 3.015e-13 | 5.24e-09 |
FAM38B | 0.4207 | 1.047e-12 | 1.82e-08 |
DLL3 | 0.4205 | 1.08e-12 | 1.88e-08 |
PATHOLOGY.N | Labels | N |
N0 | 118 | |
N1 | 9 | |
Significant markers | N = 8 | |
Higher in N1 | 1 | |
Higher in N0 | 7 |
T(pos if higher in 'N1') | ttestP | Q | AUC | |
---|---|---|---|---|
CARD16 | -6.25 | 1.428e-08 | 0.000248 | 0.6638 |
CASP1 | -6.25 | 1.428e-08 | 0.000248 | 0.6638 |
SFXN5 | -6.21 | 3.299e-07 | 0.00573 | 0.7109 |
LOC339535 | 6.16 | 7.641e-07 | 0.0133 | 0.7881 |
VGF | -5.16 | 9.519e-07 | 0.0165 | 0.6544 |
ALKBH2 | -5.09 | 1.458e-06 | 0.0253 | 0.6704 |
SYNCRIP | -5.02 | 2.001e-06 | 0.0348 | 0.7354 |
PLAG1 | -4.91 | 2.814e-06 | 0.0489 | 0.7702 |
PATHOLOGICSPREAD(M) | Labels | N |
M0 | 213 | |
M1 | 50 | |
Significant markers | N = 46 | |
Higher in M1 | 43 | |
Higher in M0 | 3 |
T(pos if higher in 'M1') | ttestP | Q | AUC | |
---|---|---|---|---|
CMTM8 | 7.28 | 1.127e-11 | 1.96e-07 | 0.7229 |
C20ORF112 | 7.2 | 2.774e-11 | 4.82e-07 | 0.7599 |
OPRK1 | 7.21 | 1.558e-10 | 2.71e-06 | 0.7607 |
HTR6 | 6.94 | 8.291e-10 | 1.44e-05 | 0.7642 |
PLCD1 | 6.33 | 1.963e-09 | 3.41e-05 | 0.7057 |
SESN1 | 6.03 | 1.465e-08 | 0.000255 | 0.7013 |
GFPT1 | 5.96 | 2.322e-08 | 0.000403 | 0.6902 |
MUSK | 5.95 | 2.423e-08 | 0.000421 | 0.7065 |
STK24 | 6.09 | 2.51e-08 | 0.000436 | 0.7486 |
ASB4 | 5.98 | 3.053e-08 | 0.00053 | 0.7233 |
TUMOR.STAGE | Mean (SD) | 2.22 (1.2) |
N | ||
Stage 1 | 119 | |
Stage 2 | 21 | |
Stage 3 | 68 | |
Stage 4 | 55 | |
Significant markers | N = 648 | |
pos. correlated | 418 | |
neg. correlated | 230 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
KDR | 0.5203 | 1.214e-19 | 2.11e-15 |
ACTA1 | 0.4863 | 5.134e-17 | 8.92e-13 |
OPRK1 | 0.4738 | 3.991e-16 | 6.93e-12 |
DBX2 | 0.4657 | 1.47e-15 | 2.56e-11 |
FAM38B | 0.4601 | 3.481e-15 | 6.05e-11 |
NR5A1 | 0.4537 | 9.253e-15 | 1.61e-10 |
DLL3 | 0.4516 | 1.267e-14 | 2.2e-10 |
AVPR1A | 0.4515 | 1.287e-14 | 2.24e-10 |
NEUROD2 | 0.4464 | 2.764e-14 | 4.8e-10 |
RRM2 | -0.4402 | 6.83e-14 | 1.19e-09 |
NEOADJUVANT.THERAPY | Labels | N |
NO | 4 | |
YES | 259 | |
Significant markers | N = 130 | |
Higher in YES | 51 | |
Higher in NO | 79 |
T(pos if higher in 'YES') | ttestP | Q | AUC | |
---|---|---|---|---|
ALDOB | -12.78 | 1.119e-24 | 1.94e-20 | 0.8243 |
NKIRAS2 | 12.69 | 2.189e-23 | 3.8e-19 | 0.8909 |
PLXNB2 | 11.55 | 6.458e-22 | 1.12e-17 | 0.7761 |
MREG | 11.5 | 6.338e-20 | 1.1e-15 | 0.7597 |
UQCRH | 9.8 | 1.679e-19 | 2.91e-15 | 0.6467 |
RDX | 20.73 | 8.317e-19 | 1.44e-14 | 0.9479 |
METTL3 | -17.65 | 1.49e-18 | 2.59e-14 | 0.8983 |
KIAA0114 | 8.87 | 5.748e-16 | 9.98e-12 | 0.7191 |
GRIN1 | -10.33 | 6.6e-16 | 1.15e-11 | 0.8485 |
GTF2A1L | -8.6 | 7.988e-16 | 1.39e-11 | 0.6525 |
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Expresson data file = KIRC.meth.for_correlation.filtered_data.txt
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Clinical data file = KIRC.clin.merged.picked.txt
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Number of patients = 263
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Number of genes = 17380
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Number of clinical features = 9
For survival clinical features, Wald's test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values using the 'coxph' function in R. Kaplan-Meier survival curves were plot using the four quartile subgroups of patients based on expression levels
For continuous numerical clinical features, Spearman's rank correlation coefficients (Spearman 1904) and two-tailed P values were estimated using 'cor.test' function in R
For two-class clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the log2-expression levels between the two clinical classes using 't.test' function in R
For multiple hypothesis correction, Q value is the False Discovery Rate (FDR) analogue of the P value (Benjamini and Hochberg 1995), defined as the minimum FDR at which the test may be called significant. We used the 'Benjamini and Hochberg' method of 'p.adjust' function in R to convert P values into Q values.
This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.