This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.
Testing the association between 17337 genes and 8 clinical features across 272 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.
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480 genes correlated to 'Time to Death'.
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FLJ42289 , TLL2 , RIOK3 , RPRD2 , ARHGEF12 , ...
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15 genes correlated to 'AGE'.
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ELOVL2 , ME3 , MRPS33 , DOK6 , TSPYL5 , ...
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69 genes correlated to 'GENDER'.
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UTP14C , KIF4B , CCDC146 , UQCRH , CAV2 , ...
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808 genes correlated to 'PATHOLOGY.T'.
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KDR , CLEC2L , OPRK1 , ACTA1 , SYN2 , ...
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9 genes correlated to 'PATHOLOGY.N'.
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CARD16 , CASP1 , SFXN5 , VGF , ZFP64 , ...
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68 genes correlated to 'PATHOLOGICSPREAD(M)'.
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C20ORF112 , OPRK1 , HTR6 , PLCD1 , NBLA00301 , ...
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884 genes correlated to 'TUMOR.STAGE'.
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KDR , UTF1 , LOC645323 , OPRK1 , CLEC2L , ...
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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=480 | shorter survival | N=293 | longer survival | N=187 |
AGE | Spearman correlation test | N=15 | older | N=12 | younger | N=3 |
GENDER | t test | N=69 | male | N=7 | female | N=62 |
KARNOFSKY PERFORMANCE SCORE | Spearman correlation test | N=0 | ||||
PATHOLOGY T | Spearman correlation test | N=808 | higher pT | N=399 | lower pT | N=409 |
PATHOLOGY N | t test | N=9 | n1 | N=2 | n0 | N=7 |
PATHOLOGICSPREAD(M) | t test | N=68 | m1 | N=62 | m0 | N=6 |
TUMOR STAGE | Spearman correlation test | N=884 | higher stage | N=559 | lower stage | N=325 |
Time to Death | Duration (Months) | 0.1-109.6 (median=27.9) |
censored | N = 177 | |
death | N = 92 | |
Significant markers | N = 480 | |
associated with shorter survival | 293 | |
associated with longer survival | 187 |
HazardRatio | Wald_P | Q | C_index | |
---|---|---|---|---|
FLJ42289 | 0.03 | 1.837e-12 | 3.2e-08 | 0.304 |
TLL2 | 0.02 | 4.808e-12 | 8.3e-08 | 0.314 |
RIOK3 | 7501 | 1.987e-11 | 3.4e-07 | 0.668 |
RPRD2 | 54 | 2.331e-11 | 4e-07 | 0.681 |
ARHGEF12 | 44 | 2.398e-11 | 4.2e-07 | 0.642 |
GRIN2D | 0 | 3.355e-11 | 5.8e-07 | 0.32 |
IGLL1 | 0.01 | 7.656e-11 | 1.3e-06 | 0.311 |
MBNL2 | 28 | 1.233e-10 | 2.1e-06 | 0.672 |
PLCB3 | 0 | 1.283e-10 | 2.2e-06 | 0.379 |
PCCA | 51 | 1.561e-10 | 2.7e-06 | 0.66 |
AGE | Mean (SD) | 61.34 (12) |
Significant markers | N = 15 | |
pos. correlated | 12 | |
neg. correlated | 3 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
ELOVL2 | 0.4681 | 3.221e-16 | 5.58e-12 |
ME3 | -0.3185 | 7.937e-08 | 0.00138 |
MRPS33 | 0.3184 | 7.954e-08 | 0.00138 |
DOK6 | 0.3171 | 9.071e-08 | 0.00157 |
TSPYL5 | 0.3157 | 1.041e-07 | 0.0018 |
ADAMTS17 | 0.3108 | 1.67e-07 | 0.00289 |
RANBP17 | 0.3048 | 2.966e-07 | 0.00514 |
ZYG11A | 0.3047 | 2.99e-07 | 0.00518 |
PVT1 | -0.3018 | 3.907e-07 | 0.00677 |
LYSMD2 | -0.2976 | 5.769e-07 | 0.01 |
GENDER | Labels | N |
FEMALE | 93 | |
MALE | 179 | |
Significant markers | N = 69 | |
Higher in MALE | 7 | |
Higher in FEMALE | 62 |
T(pos if higher in 'MALE') | ttestP | Q | AUC | |
---|---|---|---|---|
UTP14C | 17.67 | 7.204e-34 | 1.25e-29 | 0.9717 |
KIF4B | -11.84 | 5.539e-25 | 9.6e-21 | 0.8806 |
CCDC146 | -10.57 | 5.83e-22 | 1.01e-17 | 0.8016 |
UQCRH | 10.04 | 1.417e-19 | 2.46e-15 | 0.7614 |
CAV2 | -9.94 | 1.455e-19 | 2.52e-15 | 0.8024 |
DNAJB13 | -9.66 | 4.784e-19 | 8.29e-15 | 0.7821 |
C5ORF27 | -9.64 | 2.049e-18 | 3.55e-14 | 0.8035 |
TLE1 | -9.45 | 3.198e-17 | 5.54e-13 | 0.8072 |
NICN1 | -9.2 | 5.664e-17 | 9.82e-13 | 0.8059 |
COX7C | -8.77 | 8.392e-15 | 1.45e-10 | 0.809 |
No gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.
KARNOFSKY.PERFORMANCE.SCORE | Mean (SD) | 92.59 (8.1) |
Score | N | |
70 | 1 | |
80 | 3 | |
90 | 11 | |
100 | 12 | |
Significant markers | N = 0 |
PATHOLOGY.T | Mean (SD) | 1.96 (0.98) |
N | ||
T1 | 128 | |
T2 | 34 | |
T3 | 102 | |
T4 | 8 | |
Significant markers | N = 808 | |
pos. correlated | 399 | |
neg. correlated | 409 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
KDR | 0.5042 | 6.031e-19 | 1.05e-14 |
CLEC2L | 0.4782 | 6.046e-17 | 1.05e-12 |
OPRK1 | 0.4675 | 3.548e-16 | 6.15e-12 |
ACTA1 | 0.4589 | 1.436e-15 | 2.49e-11 |
SYN2 | 0.4447 | 1.292e-14 | 2.24e-10 |
NEUROD2 | 0.4434 | 1.581e-14 | 2.74e-10 |
AVPR1A | 0.4427 | 1.759e-14 | 3.05e-10 |
UTF1 | 0.4407 | 2.363e-14 | 4.1e-10 |
LOC645323 | 0.4489 | 2.413e-14 | 4.18e-10 |
SLC35F1 | 0.4393 | 2.929e-14 | 5.08e-10 |
PATHOLOGY.N | Labels | N |
N0 | 122 | |
N1 | 9 | |
Significant markers | N = 9 | |
Higher in N1 | 2 | |
Higher in N0 | 7 |
T(pos if higher in 'N1') | ttestP | Q | AUC | |
---|---|---|---|---|
CARD16 | -6.43 | 6.705e-09 | 0.000116 | 0.6648 |
CASP1 | -6.43 | 6.705e-09 | 0.000116 | 0.6648 |
SFXN5 | -6.15 | 4.185e-07 | 0.00725 | 0.7049 |
VGF | -5.23 | 6.713e-07 | 0.0116 | 0.6594 |
ZFP64 | -5.25 | 6.953e-07 | 0.0121 | 0.6266 |
CYP27C1 | 5.19 | 1.082e-06 | 0.0188 | 0.6803 |
TSPO | -5.37 | 1.108e-06 | 0.0192 | 0.6266 |
PLAG1 | -4.97 | 2.112e-06 | 0.0366 | 0.7696 |
LOC150568 | 5.4 | 2.289e-06 | 0.0397 | 0.742 |
PATHOLOGICSPREAD(M) | Labels | N |
M0 | 221 | |
M1 | 51 | |
Significant markers | N = 68 | |
Higher in M1 | 62 | |
Higher in M0 | 6 |
T(pos if higher in 'M1') | ttestP | Q | AUC | |
---|---|---|---|---|
C20ORF112 | 7.56 | 3.47e-12 | 6.02e-08 | 0.7674 |
OPRK1 | 7.56 | 2.711e-11 | 4.7e-07 | 0.769 |
HTR6 | 7.33 | 1.327e-10 | 2.3e-06 | 0.773 |
PLCD1 | 6.64 | 3.601e-10 | 6.24e-06 | 0.7151 |
NBLA00301 | 6.47 | 4.007e-09 | 6.94e-05 | 0.726 |
MUSK | 6.27 | 4.755e-09 | 8.24e-05 | 0.7137 |
SESN1 | 6.25 | 4.926e-09 | 8.54e-05 | 0.7077 |
PDGFB | 6.14 | 7.019e-09 | 0.000122 | 0.7197 |
STK24 | 6.35 | 7.347e-09 | 0.000127 | 0.7532 |
ASB4 | 6.08 | 1.011e-08 | 0.000175 | 0.694 |
TUMOR.STAGE | Mean (SD) | 2.2 (1.2) |
N | ||
Stage 1 | 126 | |
Stage 2 | 22 | |
Stage 3 | 68 | |
Stage 4 | 56 | |
Significant markers | N = 884 | |
pos. correlated | 559 | |
neg. correlated | 325 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
KDR | 0.5281 | 6.164e-21 | 1.07e-16 |
UTF1 | 0.4971 | 2.218e-18 | 3.84e-14 |
LOC645323 | 0.5017 | 4.807e-18 | 8.33e-14 |
OPRK1 | 0.4921 | 5.436e-18 | 9.42e-14 |
CLEC2L | 0.4888 | 9.614e-18 | 1.67e-13 |
ACTA1 | 0.4879 | 1.125e-17 | 1.95e-13 |
NEUROD2 | 0.4833 | 2.516e-17 | 4.36e-13 |
SYN2 | 0.4751 | 1.016e-16 | 1.76e-12 |
AVPR1A | 0.468 | 3.259e-16 | 5.65e-12 |
FAM38B | 0.4676 | 3.507e-16 | 6.08e-12 |
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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 = 272
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Number of genes = 17337
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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.