This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.
Testing the association between 17341 genes and 8 clinical features across 263 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.
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442 genes correlated to 'Time to Death'.
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FLJ42289 , TLL2 , PPP3CB , ARHGEF12 , RPRD2 , ...
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16 genes correlated to 'AGE'.
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ELOVL2 , MRPS33 , UNC80 , DOK6 , RANBP17 , ...
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77 genes correlated to 'GENDER'.
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UTP14C , KIF4B , CCDC146 , CAV2 , C5ORF27 , ...
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647 genes correlated to 'PATHOLOGY.T'.
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KDR , DBX2 , OPRK1 , ACTA1 , NEUROD2 , ...
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6 genes correlated to 'PATHOLOGY.N'.
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CARD16 , CASP1 , SFXN5 , VGF , ZFP64 , ...
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53 genes correlated to 'PATHOLOGICSPREAD(M)'.
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C20ORF112 , OPRK1 , HTR6 , PLCD1 , SESN1 , ...
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720 genes correlated to 'TUMOR.STAGE'.
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KDR , NEUROD2 , OPRK1 , ACTA1 , DBX2 , ...
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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=442 | shorter survival | N=273 | longer survival | N=169 |
AGE | Spearman correlation test | N=16 | older | N=13 | younger | N=3 |
GENDER | t test | N=77 | male | N=7 | female | N=70 |
KARNOFSKY PERFORMANCE SCORE | Spearman correlation test | N=0 | ||||
PATHOLOGY T | Spearman correlation test | N=647 | higher pT | N=321 | lower pT | N=326 |
PATHOLOGY N | t test | N=6 | n1 | N=0 | n0 | N=6 |
PATHOLOGICSPREAD(M) | t test | N=53 | m1 | N=50 | m0 | N=3 |
TUMOR STAGE | Spearman correlation test | N=720 | higher stage | N=479 | lower stage | N=241 |
Time to Death | Duration (Months) | 0.1-109.6 (median=28) |
censored | N = 168 | |
death | N = 92 | |
Significant markers | N = 442 | |
associated with shorter survival | 273 | |
associated with longer survival | 169 |
HazardRatio | Wald_P | Q | C_index | |
---|---|---|---|---|
FLJ42289 | 0.03 | 4.452e-12 | 7.7e-08 | 0.305 |
TLL2 | 0.02 | 1.049e-11 | 1.8e-07 | 0.317 |
PPP3CB | 0 | 1.299e-11 | 2.3e-07 | 0.328 |
ARHGEF12 | 42 | 4.166e-11 | 7.2e-07 | 0.641 |
RPRD2 | 51 | 4.305e-11 | 7.5e-07 | 0.679 |
RIOK3 | 6001 | 7.395e-11 | 1.3e-06 | 0.663 |
GRIN2D | 0 | 7.721e-11 | 1.3e-06 | 0.323 |
IFFO1 | 0 | 8.133e-11 | 1.4e-06 | 0.347 |
PCCA | 52 | 9.75e-11 | 1.7e-06 | 0.662 |
MBNL2 | 28 | 1.28e-10 | 2.2e-06 | 0.671 |
AGE | Mean (SD) | 61.4 (12) |
Significant markers | N = 16 | |
pos. correlated | 13 | |
neg. correlated | 3 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
ELOVL2 | 0.4688 | 9.003e-16 | 1.56e-11 |
MRPS33 | 0.3349 | 2.597e-08 | 0.00045 |
UNC80 | 0.3255 | 6.63e-08 | 0.00115 |
DOK6 | 0.3192 | 1.219e-07 | 0.00211 |
RANBP17 | 0.3137 | 2.057e-07 | 0.00357 |
ADAMTS17 | 0.3082 | 3.411e-07 | 0.00591 |
ME3 | -0.3082 | 3.419e-07 | 0.00593 |
TSPYL5 | 0.307 | 3.82e-07 | 0.00662 |
C7ORF13 | 0.3021 | 5.967e-07 | 0.0103 |
RNF32 | 0.3021 | 5.967e-07 | 0.0103 |
GENDER | Labels | N |
FEMALE | 89 | |
MALE | 174 | |
Significant markers | N = 77 | |
Higher in MALE | 7 | |
Higher in FEMALE | 70 |
T(pos if higher in 'MALE') | ttestP | Q | AUC | |
---|---|---|---|---|
UTP14C | 17.15 | 3.338e-32 | 5.79e-28 | 0.9706 |
KIF4B | -11.32 | 3.515e-23 | 6.1e-19 | 0.875 |
CCDC146 | -10.41 | 2.327e-21 | 4.03e-17 | 0.802 |
CAV2 | -9.92 | 2.081e-19 | 3.61e-15 | 0.8065 |
C5ORF27 | -9.78 | 9.021e-19 | 1.56e-14 | 0.8085 |
UQCRH | 9.75 | 1.145e-18 | 1.98e-14 | 0.7601 |
DNAJB13 | -9.4 | 3.922e-18 | 6.8e-14 | 0.7811 |
TLE1 | -9.16 | 2.634e-16 | 4.57e-12 | 0.8047 |
ADAMTS10 | -8.02 | 3.575e-14 | 6.2e-10 | 0.7323 |
CHTF8 | 8.23 | 4.86e-14 | 8.42e-10 | 0.811 |
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 (0.98) |
N | ||
T1 | 120 | |
T2 | 33 | |
T3 | 102 | |
T4 | 8 | |
Significant markers | N = 647 | |
pos. correlated | 321 | |
neg. correlated | 326 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
KDR | 0.4954 | 1.081e-17 | 1.88e-13 |
DBX2 | 0.4619 | 2.639e-15 | 4.58e-11 |
OPRK1 | 0.4583 | 4.608e-15 | 7.99e-11 |
ACTA1 | 0.4526 | 1.093e-14 | 1.89e-10 |
NEUROD2 | 0.4459 | 2.966e-14 | 5.14e-10 |
AVPR1A | 0.4324 | 2.082e-13 | 3.61e-09 |
SLC35F1 | 0.4308 | 2.616e-13 | 4.54e-09 |
RRM2 | -0.4302 | 2.841e-13 | 4.92e-09 |
DSC3 | 0.4188 | 1.364e-12 | 2.36e-08 |
FAM38B | 0.4185 | 1.426e-12 | 2.47e-08 |
PATHOLOGY.N | Labels | N |
N0 | 118 | |
N1 | 9 | |
Significant markers | N = 6 | |
Higher in N1 | 0 | |
Higher in N0 | 6 |
T(pos if higher in 'N1') | ttestP | Q | AUC | |
---|---|---|---|---|
CARD16 | -6.22 | 1.661e-08 | 0.000288 | 0.6582 |
CASP1 | -6.22 | 1.661e-08 | 0.000288 | 0.6582 |
SFXN5 | -6.17 | 3.723e-07 | 0.00645 | 0.7109 |
VGF | -5.22 | 7.276e-07 | 0.0126 | 0.6629 |
ZFP64 | -5.19 | 9.117e-07 | 0.0158 | 0.6252 |
PLAG1 | -4.93 | 2.598e-06 | 0.045 | 0.7702 |
PATHOLOGICSPREAD(M) | Labels | N |
M0 | 212 | |
M1 | 51 | |
Significant markers | N = 53 | |
Higher in M1 | 50 | |
Higher in M0 | 3 |
T(pos if higher in 'M1') | ttestP | Q | AUC | |
---|---|---|---|---|
C20ORF112 | 7.35 | 1.047e-11 | 1.82e-07 | 0.7646 |
OPRK1 | 7.41 | 5.015e-11 | 8.7e-07 | 0.7662 |
HTR6 | 7.14 | 2.833e-10 | 4.91e-06 | 0.7689 |
PLCD1 | 6.46 | 8.995e-10 | 1.56e-05 | 0.7108 |
SESN1 | 6.17 | 6.789e-09 | 0.000118 | 0.7053 |
MUSK | 6.07 | 1.192e-08 | 0.000207 | 0.7091 |
NBLA00301 | 6.22 | 1.197e-08 | 0.000208 | 0.7195 |
STK24 | 6.23 | 1.202e-08 | 0.000208 | 0.7508 |
ASB4 | 6.15 | 1.279e-08 | 0.000222 | 0.7278 |
CSDC2 | 6.12 | 2.727e-08 | 0.000473 | 0.7388 |
TUMOR.STAGE | Mean (SD) | 2.24 (1.2) |
N | ||
Stage 1 | 118 | |
Stage 2 | 21 | |
Stage 3 | 68 | |
Stage 4 | 56 | |
Significant markers | N = 720 | |
pos. correlated | 479 | |
neg. correlated | 241 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
KDR | 0.5212 | 1.013e-19 | 1.76e-15 |
NEUROD2 | 0.4884 | 3.579e-17 | 6.21e-13 |
OPRK1 | 0.4852 | 6.192e-17 | 1.07e-12 |
ACTA1 | 0.4832 | 8.596e-17 | 1.49e-12 |
DBX2 | 0.4731 | 4.521e-16 | 7.84e-12 |
FAM38B | 0.4622 | 2.525e-15 | 4.38e-11 |
AVPR1A | 0.4598 | 3.651e-15 | 6.33e-11 |
DLL3 | 0.455 | 7.634e-15 | 1.32e-10 |
C20ORF112 | 0.4422 | 5.124e-14 | 8.88e-10 |
RRM2 | -0.4398 | 7.247e-14 | 1.26e-09 |
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Expresson data file = KIRC-TP.meth.for_correlation.filtered_data.txt
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Clinical data file = KIRC-TP.clin.merged.picked.txt
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Number of patients = 263
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Number of genes = 17341
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Number of clinical features = 8
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.