This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.
Testing the association between 20182 genes and 7 clinical features across 283 samples, statistically thresholded by Q value < 0.05, 6 clinical features related to at least one genes.
-
415 genes correlated to 'Time to Death'.
-
FLJ42289 , RIOK3 , TLL2 , RPRD2 , IGLL1 , ...
-
19 genes correlated to 'AGE'.
-
ELOVL2 , MRPS33 , TSPYL5 , DOK6 , ZYG11A , ...
-
97 genes correlated to 'GENDER'.
-
ALG11__1 , UTP14C , KIF4B , CCDC146__1 , DNAJB13 , ...
-
81 genes correlated to 'DISTANT.METASTASIS'.
-
C20ORF112 , OPRK1 , HTR6 , PLCD1 , MUSK , ...
-
1 gene correlated to 'LYMPH.NODE.METASTASIS'.
-
LIN7B
-
554 genes correlated to 'NEOPLASM.DISEASESTAGE'.
-
KDR , OPRK1 , FAM38B , AVPR1A , CLEC2L , ...
-
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=415 | shorter survival | N=240 | longer survival | N=175 |
AGE | Spearman correlation test | N=19 | older | N=15 | younger | N=4 |
GENDER | t test | N=97 | male | N=11 | female | N=86 |
KARNOFSKY PERFORMANCE SCORE | Spearman correlation test | N=0 | ||||
DISTANT METASTASIS | t test | N=81 | m1 | N=73 | m0 | N=8 |
LYMPH NODE METASTASIS | ANOVA test | N=1 | ||||
NEOPLASM DISEASESTAGE | ANOVA test | N=554 |
Time to Death | Duration (Months) | 0.1-109.9 (median=28.6) |
censored | N = 186 | |
death | N = 94 | |
Significant markers | N = 415 | |
associated with shorter survival | 240 | |
associated with longer survival | 175 |
HazardRatio | Wald_P | Q | C_index | |
---|---|---|---|---|
FLJ42289 | 0.03 | 1.546e-12 | 3.1e-08 | 0.303 |
RIOK3 | 10001 | 2.126e-12 | 4.3e-08 | 0.674 |
TLL2 | 0.02 | 3.526e-12 | 7.1e-08 | 0.315 |
RPRD2 | 56 | 1.447e-11 | 2.9e-07 | 0.681 |
IGLL1 | 0.01 | 4.475e-11 | 9e-07 | 0.309 |
PLCB3 | 0 | 6.929e-11 | 1.4e-06 | 0.374 |
CCL26 | 0.06 | 8.598e-11 | 1.7e-06 | 0.353 |
CLEC2L | 16 | 1.139e-10 | 2.3e-06 | 0.675 |
ARHGEF12 | 40 | 1.166e-10 | 2.4e-06 | 0.64 |
EVI2A | 0.04 | 1.253e-10 | 2.5e-06 | 0.346 |
AGE | Mean (SD) | 61.49 (12) |
Significant markers | N = 19 | |
pos. correlated | 15 | |
neg. correlated | 4 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
ELOVL2 | 0.4668 | 1.021e-16 | 2.06e-12 |
MRPS33 | 0.3343 | 8.161e-09 | 0.000165 |
TSPYL5 | 0.3272 | 1.74e-08 | 0.000351 |
DOK6 | 0.322 | 3.012e-08 | 0.000608 |
ZYG11A | 0.3187 | 4.237e-08 | 0.000855 |
ME3 | -0.3138 | 6.93e-08 | 0.0014 |
PVT1 | -0.3102 | 9.963e-08 | 0.00201 |
RANBP17 | 0.309 | 1.123e-07 | 0.00226 |
ADAMTS17 | 0.3002 | 2.651e-07 | 0.00535 |
SLC10A4 | 0.299 | 2.969e-07 | 0.00599 |
GENDER | Labels | N |
FEMALE | 96 | |
MALE | 187 | |
Significant markers | N = 97 | |
Higher in MALE | 11 | |
Higher in FEMALE | 86 |
T(pos if higher in 'MALE') | ttestP | Q | AUC | |
---|---|---|---|---|
ALG11__1 | 18.74 | 8.723e-35 | 1.76e-30 | 0.9806 |
UTP14C | 18.74 | 8.723e-35 | 1.76e-30 | 0.9806 |
KIF4B | -12.12 | 6.544e-26 | 1.32e-21 | 0.8809 |
CCDC146__1 | -10.93 | 3.001e-23 | 6.06e-19 | 0.8112 |
DNAJB13 | -10.18 | 9e-21 | 1.82e-16 | 0.7948 |
C5ORF27 | -10.31 | 1.602e-20 | 3.23e-16 | 0.8155 |
LRRC41 | 10.24 | 2.051e-20 | 4.14e-16 | 0.7638 |
UQCRH | 10.24 | 2.051e-20 | 4.14e-16 | 0.7638 |
CAV2 | -9.78 | 4.191e-19 | 8.46e-15 | 0.7968 |
TLE1 | -10.01 | 6.611e-19 | 1.33e-14 | 0.8158 |
No gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.
KARNOFSKY.PERFORMANCE.SCORE | Mean (SD) | 92.5 (8) |
Score | N | |
70 | 1 | |
80 | 3 | |
90 | 12 | |
100 | 12 | |
Significant markers | N = 0 |
DISTANT.METASTASIS | Labels | N |
M0 | 232 | |
M1 | 51 | |
Significant markers | N = 81 | |
Higher in M1 | 73 | |
Higher in M0 | 8 |
T(pos if higher in 'M1') | ttestP | Q | AUC | |
---|---|---|---|---|
C20ORF112 | 7.64 | 2.497e-12 | 5.04e-08 | 0.7658 |
OPRK1 | 7.41 | 6.057e-11 | 1.22e-06 | 0.7618 |
HTR6 | 7.36 | 1.229e-10 | 2.48e-06 | 0.7727 |
PLCD1 | 6.55 | 6.293e-10 | 1.27e-05 | 0.7116 |
MUSK | 6.28 | 4.971e-09 | 1e-04 | 0.7143 |
SESN1__1 | 6.21 | 6.506e-09 | 0.000131 | 0.7059 |
STK24 | 6.38 | 6.719e-09 | 0.000136 | 0.7535 |
ASB4 | 6.09 | 1.01e-08 | 0.000204 | 0.695 |
PDGFB | 6.07 | 1.061e-08 | 0.000214 | 0.7147 |
HAND2__1 | 6.25 | 1.185e-08 | 0.000239 | 0.7159 |
LYMPH.NODE.METASTASIS | Labels | N |
N0 | 127 | |
N1 | 9 | |
NX | 147 | |
Significant markers | N = 1 |
ANOVA_P | Q | |
---|---|---|
LIN7B | 1.884e-06 | 0.038 |
NEOPLASM.DISEASESTAGE | Labels | N |
STAGE I | 129 | |
STAGE II | 27 | |
STAGE III | 74 | |
STAGE IV | 53 | |
Significant markers | N = 554 |
ANOVA_P | Q | |
---|---|---|
KDR | 3.06e-20 | 6.17e-16 |
OPRK1 | 1.202e-18 | 2.43e-14 |
FAM38B | 2.691e-16 | 5.43e-12 |
AVPR1A | 3.051e-16 | 6.16e-12 |
CLEC2L | 8.466e-15 | 1.71e-10 |
PCDHGA1__5 | 3.72e-14 | 7.51e-10 |
PCDHGA10__3 | 3.72e-14 | 7.51e-10 |
PCDHGA11__2 | 3.72e-14 | 7.51e-10 |
PCDHGA2__5 | 3.72e-14 | 7.51e-10 |
PCDHGA3__5 | 3.72e-14 | 7.51e-10 |
-
Expresson data file = KIRC-TP.meth.by_min_expr_corr.data.txt
-
Clinical data file = KIRC-TP.clin.merged.picked.txt
-
Number of patients = 283
-
Number of genes = 20182
-
Number of clinical features = 7
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 multi-class clinical features (ordinal or nominal), one-way analysis of variance (Howell 2002) was applied to compare the log2-expression levels between different clinical classes using 'anova' 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.