This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.
Testing the association between 19697 genes and 15 clinical features across 484 samples, statistically thresholded by Q value < 0.05, 12 clinical features related to at least one genes.
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377 genes correlated to 'AGE'.
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MGA , NHLRC1 , INA , RANBP17 , SYNGR3 , ...
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415 genes correlated to 'NEOPLASM.DISEASESTAGE'.
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OTOS , C1ORF91__1 , EIF3I__1 , ACTA1 , C10ORF137 , ...
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157 genes correlated to 'PATHOLOGY.T.STAGE'.
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TBKBP1 , IFT140 , TMEM204 , GJD3 , PDGFB , ...
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1316 genes correlated to 'PATHOLOGY.N.STAGE'.
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PON2 , CPNE1__1 , RBM12__1 , BMP1 , MACF1 , ...
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22 genes correlated to 'PATHOLOGY.M.STAGE'.
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C1ORF91__1 , EIF3I__1 , LCA5 , KCTD12 , GPI , ...
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28 genes correlated to 'GENDER'.
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ALG11__2 , UTP14C__1 , ETF1 , KIF4B , CHTF8 , ...
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2248 genes correlated to 'HISTOLOGICAL.TYPE'.
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PON2 , EMP1 , SLC6A12 , LEPR , LEPROT , ...
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49 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
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SIK1 , SNX31 , STX17 , TAF7 , KIAA1143__1 , ...
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52 genes correlated to 'RADIATIONEXPOSURE'.
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CHEK2 , HSCB , MGC21881 , CASP12 , TMEM63C , ...
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352 genes correlated to 'EXTRATHYROIDAL.EXTENSION'.
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OTOS , DEFB131 , TBX19 , SLC16A3 , SEC22C , ...
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14 genes correlated to 'COMPLETENESS.OF.RESECTION'.
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CAPN5__1 , OMP , ANKRD34B , ASTN2 , EPHA7 , ...
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1047 genes correlated to 'NUMBER.OF.LYMPH.NODES'.
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FUT2 , TMEM173 , MET , TAGLN2 , MACF1 , ...
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No genes correlated to 'Time to Death', 'MULTIFOCALITY', and 'TUMOR.SIZE'.
Complete statistical result table is provided in Supplement Table 1
Table 1. Get Full Table This table shows the clinical features, statistical methods used, and the number of genes that are significantly associated with each clinical feature at Q value < 0.05.
Clinical feature | Statistical test | Significant genes | Associated with | Associated with | ||
---|---|---|---|---|---|---|
Time to Death | Cox regression test | N=0 | ||||
AGE | Spearman correlation test | N=377 | older | N=376 | younger | N=1 |
NEOPLASM DISEASESTAGE | ANOVA test | N=415 | ||||
PATHOLOGY T STAGE | Spearman correlation test | N=157 | higher stage | N=75 | lower stage | N=82 |
PATHOLOGY N STAGE | t test | N=1316 | class1 | N=138 | class0 | N=1178 |
PATHOLOGY M STAGE | ANOVA test | N=22 | ||||
GENDER | t test | N=28 | male | N=15 | female | N=13 |
HISTOLOGICAL TYPE | ANOVA test | N=2248 | ||||
RADIATIONS RADIATION REGIMENINDICATION | t test | N=49 | yes | N=25 | no | N=24 |
RADIATIONEXPOSURE | t test | N=52 | yes | N=23 | no | N=29 |
EXTRATHYROIDAL EXTENSION | ANOVA test | N=352 | ||||
COMPLETENESS OF RESECTION | ANOVA test | N=14 | ||||
NUMBER OF LYMPH NODES | Spearman correlation test | N=1047 | higher number.of.lymph.nodes | N=24 | lower number.of.lymph.nodes | N=1023 |
MULTIFOCALITY | t test | N=0 | ||||
TUMOR SIZE | Spearman correlation test | N=0 |
Table S1. Basic characteristics of clinical feature: 'Time to Death'
Time to Death | Duration (Months) | 0-158.8 (median=14.8) |
censored | N = 465 | |
death | N = 14 | |
Significant markers | N = 0 |
Table S2. Basic characteristics of clinical feature: 'AGE'
AGE | Mean (SD) | 47.17 (16) |
Significant markers | N = 377 | |
pos. correlated | 376 | |
neg. correlated | 1 |
Table S3. Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
MGA | 0.5287 | 3.373e-36 | 6.64e-32 |
NHLRC1 | 0.4893 | 1.685e-30 | 3.32e-26 |
INA | 0.4785 | 4.643e-29 | 9.14e-25 |
RANBP17 | 0.4609 | 7.971e-27 | 1.57e-22 |
SYNGR3 | 0.4591 | 1.305e-26 | 2.57e-22 |
C1ORF59 | 0.4553 | 3.877e-26 | 7.64e-22 |
ACN9 | 0.4493 | 2.028e-25 | 3.99e-21 |
OTUD7A | 0.4322 | 1.921e-23 | 3.78e-19 |
ZNF518B | 0.431 | 2.599e-23 | 5.12e-19 |
NTNG2 | 0.4268 | 7.54e-23 | 1.48e-18 |
Figure S1. Get High-res Image As an example, this figure shows the association of MGA to 'AGE'. P value = 3.37e-36 with Spearman correlation analysis. The straight line presents the best linear regression.
![](V2ex.png)
Table S4. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'
NEOPLASM.DISEASESTAGE | Labels | N |
STAGE I | 274 | |
STAGE II | 51 | |
STAGE III | 106 | |
STAGE IV | 2 | |
STAGE IVA | 43 | |
STAGE IVC | 6 | |
Significant markers | N = 415 |
Table S5. Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'
ANOVA_P | Q | |
---|---|---|
OTOS | 9.472e-30 | 1.87e-25 |
C1ORF91__1 | 1.892e-27 | 3.73e-23 |
EIF3I__1 | 1.892e-27 | 3.73e-23 |
ACTA1 | 5.109e-27 | 1.01e-22 |
C10ORF137 | 5.648e-23 | 1.11e-18 |
RABL2A | 4.786e-16 | 9.42e-12 |
RPL23AP7 | 4.786e-16 | 9.42e-12 |
SFRP1 | 1.189e-14 | 2.34e-10 |
CHAT__1 | 1.22e-14 | 2.4e-10 |
SLC18A3__1 | 1.22e-14 | 2.4e-10 |
Figure S2. Get High-res Image As an example, this figure shows the association of OTOS to 'NEOPLASM.DISEASESTAGE'. P value = 9.47e-30 with ANOVA analysis.
![](V3ex.png)
Table S6. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'
PATHOLOGY.T.STAGE | Mean (SD) | 2.13 (0.88) |
N | ||
1 | 140 | |
2 | 161 | |
3 | 160 | |
4 | 21 | |
Significant markers | N = 157 | |
pos. correlated | 75 | |
neg. correlated | 82 |
Table S7. Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
TBKBP1 | 0.3188 | 7.542e-13 | 1.49e-08 |
IFT140 | 0.3057 | 6.979e-12 | 1.37e-07 |
TMEM204 | 0.3057 | 6.979e-12 | 1.37e-07 |
GJD3 | 0.3041 | 9.028e-12 | 1.78e-07 |
PDGFB | 0.2995 | 1.9e-11 | 3.74e-07 |
CKMT2 | 0.2819 | 2.938e-10 | 5.79e-06 |
RNU5D__1 | 0.2819 | 2.938e-10 | 5.79e-06 |
RNU5E__1 | 0.2819 | 2.938e-10 | 5.79e-06 |
PSD3 | -0.2733 | 1.055e-09 | 2.08e-05 |
FLJ42875 | 0.2725 | 1.19e-09 | 2.34e-05 |
Figure S3. Get High-res Image As an example, this figure shows the association of TBKBP1 to 'PATHOLOGY.T.STAGE'. P value = 7.54e-13 with Spearman correlation analysis.
![](V4ex.png)
Table S8. Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'
PATHOLOGY.N.STAGE | Labels | N |
class0 | 220 | |
class1 | 217 | |
Significant markers | N = 1316 | |
Higher in class1 | 138 | |
Higher in class0 | 1178 |
Table S9. Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'
T(pos if higher in 'class1') | ttestP | Q | AUC | |
---|---|---|---|---|
PON2 | -9.92 | 6.55e-21 | 1.29e-16 | 0.7366 |
CPNE1__1 | -9.89 | 7.356e-21 | 1.45e-16 | 0.7401 |
RBM12__1 | -9.89 | 7.356e-21 | 1.45e-16 | 0.7401 |
BMP1 | -9.88 | 7.413e-21 | 1.46e-16 | 0.7385 |
MACF1 | -9.9 | 8.006e-21 | 1.58e-16 | 0.7349 |
DAGLA | -9.79 | 1.506e-20 | 2.97e-16 | 0.7392 |
XDH | -9.55 | 1.309e-19 | 2.58e-15 | 0.7257 |
EPHA4 | -9.53 | 1.788e-19 | 3.52e-15 | 0.7227 |
ADAMTS17 | -9.4 | 4.279e-19 | 8.43e-15 | 0.7255 |
C8ORF73 | -9.43 | 4.749e-19 | 9.35e-15 | 0.7167 |
Figure S4. Get High-res Image As an example, this figure shows the association of PON2 to 'PATHOLOGY.N.STAGE'. P value = 6.55e-21 with T-test analysis.
![](V5ex.png)
Table S10. Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'
PATHOLOGY.M.STAGE | Labels | N |
M0 | 265 | |
M1 | 9 | |
MX | 209 | |
Significant markers | N = 22 |
Table S11. Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'
ANOVA_P | Q | |
---|---|---|
C1ORF91__1 | 5.262e-17 | 1.04e-12 |
EIF3I__1 | 5.262e-17 | 1.04e-12 |
LCA5 | 1.013e-10 | 2e-06 |
KCTD12 | 5.886e-10 | 1.16e-05 |
GPI | 8.923e-10 | 1.76e-05 |
C17ORF65__1 | 1.113e-09 | 2.19e-05 |
TMUB2__1 | 1.113e-09 | 2.19e-05 |
RPS10 | 4.357e-08 | 0.000858 |
CAPN5__1 | 1.192e-07 | 0.00235 |
OMP | 1.192e-07 | 0.00235 |
Figure S5. Get High-res Image As an example, this figure shows the association of C1ORF91__1 to 'PATHOLOGY.M.STAGE'. P value = 5.26e-17 with ANOVA analysis.
![](V6ex.png)
Table S12. Basic characteristics of clinical feature: 'GENDER'
GENDER | Labels | N |
FEMALE | 355 | |
MALE | 129 | |
Significant markers | N = 28 | |
Higher in MALE | 15 | |
Higher in FEMALE | 13 |
Table S13. Get Full Table List of top 10 genes differentially expressed by 'GENDER'
T(pos if higher in 'MALE') | ttestP | Q | AUC | |
---|---|---|---|---|
ALG11__2 | 42.37 | 5.547e-157 | 1.09e-152 | 0.9953 |
UTP14C__1 | 42.37 | 5.547e-157 | 1.09e-152 | 0.9953 |
ETF1 | 31.79 | 2.235e-81 | 4.4e-77 | 0.987 |
KIF4B | -18.21 | 2.242e-48 | 4.42e-44 | 0.904 |
CHTF8 | 11.83 | 2.005e-26 | 3.95e-22 | 0.8197 |
HAS3__1 | 11.83 | 2.005e-26 | 3.95e-22 | 0.8197 |
FAM35A | -11.32 | 2.506e-25 | 4.93e-21 | 0.8459 |
GLUD1__1 | -11.32 | 2.506e-25 | 4.93e-21 | 0.8459 |
WBP11P1 | 9.85 | 7.151e-19 | 1.41e-14 | 0.8057 |
ANKRD20A4 | 8.82 | 1.002e-16 | 1.97e-12 | 0.7421 |
Figure S6. Get High-res Image As an example, this figure shows the association of ALG11__2 to 'GENDER'. P value = 5.55e-157 with T-test analysis.
![](V7ex.png)
Table S14. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'
HISTOLOGICAL.TYPE | Labels | N |
OTHER SPECIFY | 9 | |
THYROID PAPILLARY CARCINOMA - CLASSICAL/USUAL | 341 | |
THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED) | 99 | |
THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES) | 35 | |
Significant markers | N = 2248 |
Table S15. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'
ANOVA_P | Q | |
---|---|---|
PON2 | 7.927e-42 | 1.56e-37 |
EMP1 | 3.722e-41 | 7.33e-37 |
SLC6A12 | 2.66e-40 | 5.24e-36 |
LEPR | 1.123e-39 | 2.21e-35 |
LEPROT | 1.123e-39 | 2.21e-35 |
C8ORF73 | 1.996e-39 | 3.93e-35 |
LAMP3 | 3.129e-39 | 6.16e-35 |
LOC100126784 | 2.522e-38 | 4.96e-34 |
NAV2__1 | 2.522e-38 | 4.96e-34 |
C5ORF62 | 1.627e-37 | 3.2e-33 |
Figure S7. Get High-res Image As an example, this figure shows the association of PON2 to 'HISTOLOGICAL.TYPE'. P value = 7.93e-42 with ANOVA analysis.
![](V8ex.png)
49 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
Table S16. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'
RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N |
NO | 14 | |
YES | 470 | |
Significant markers | N = 49 | |
Higher in YES | 25 | |
Higher in NO | 24 |
Table S17. Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'
T(pos if higher in 'YES') | ttestP | Q | AUC | |
---|---|---|---|---|
SIK1 | 9.64 | 1.471e-19 | 2.9e-15 | 0.6948 |
SNX31 | 8.35 | 1.583e-15 | 3.12e-11 | 0.702 |
STX17 | 9.31 | 1.072e-13 | 2.11e-09 | 0.6304 |
TAF7 | 7.93 | 1.554e-13 | 3.06e-09 | 0.7036 |
KIAA1143__1 | 8.88 | 3.727e-13 | 7.34e-09 | 0.7409 |
KIF15__1 | 8.88 | 3.727e-13 | 7.34e-09 | 0.7409 |
MYOM2 | 8.19 | 1.762e-12 | 3.47e-08 | 0.5327 |
HORMAD1 | -8.62 | 2.647e-11 | 5.21e-07 | 0.7223 |
ZNHIT3 | 7.03 | 1.613e-10 | 3.18e-06 | 0.5616 |
CBLN1 | 7.21 | 2.06e-10 | 4.06e-06 | 0.7304 |
Figure S8. Get High-res Image As an example, this figure shows the association of SIK1 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 1.47e-19 with T-test analysis.
![](V9ex.png)
Table S18. Basic characteristics of clinical feature: 'RADIATIONEXPOSURE'
RADIATIONEXPOSURE | Labels | N |
NO | 408 | |
YES | 17 | |
Significant markers | N = 52 | |
Higher in YES | 23 | |
Higher in NO | 29 |
Table S19. Get Full Table List of top 10 genes differentially expressed by 'RADIATIONEXPOSURE'
T(pos if higher in 'YES') | ttestP | Q | AUC | |
---|---|---|---|---|
CHEK2 | -7.35 | 2.53e-12 | 4.98e-08 | 0.6034 |
HSCB | -7.35 | 2.53e-12 | 4.98e-08 | 0.6034 |
MGC21881 | -7.35 | 7.185e-12 | 1.42e-07 | 0.5864 |
CASP12 | -7.58 | 4.546e-11 | 8.95e-07 | 0.6064 |
TMEM63C | -7.38 | 1.017e-10 | 2e-06 | 0.6251 |
HESX1 | 7.13 | 1.982e-10 | 3.9e-06 | 0.6674 |
CYP3A4 | 7.52 | 2.333e-10 | 4.59e-06 | 0.6671 |
POLR2F | 7.4 | 3.937e-10 | 7.75e-06 | 0.6752 |
PHKB | 6.61 | 5.657e-10 | 1.11e-05 | 0.7206 |
SLAMF9 | 7.69 | 4.187e-09 | 8.24e-05 | 0.6684 |
Figure S9. Get High-res Image As an example, this figure shows the association of CHEK2 to 'RADIATIONEXPOSURE'. P value = 2.53e-12 with T-test analysis.
![](V10ex.png)
Table S20. Basic characteristics of clinical feature: 'EXTRATHYROIDAL.EXTENSION'
EXTRATHYROIDAL.EXTENSION | Labels | N |
MINIMAL (T3) | 126 | |
MODERATE/ADVANCED (T4A) | 16 | |
NONE | 324 | |
VERY ADVANCED (T4B) | 1 | |
Significant markers | N = 352 |
Table S21. Get Full Table List of top 10 genes differentially expressed by 'EXTRATHYROIDAL.EXTENSION'
ANOVA_P | Q | |
---|---|---|
OTOS | 2.55e-72 | 5.02e-68 |
DEFB131 | 2.128e-32 | 4.19e-28 |
TBX19 | 7.942e-24 | 1.56e-19 |
SLC16A3 | 9.522e-20 | 1.88e-15 |
SEC22C | 3.075e-18 | 6.06e-14 |
PA2G4P4 | 3.262e-18 | 6.42e-14 |
TRAM1L1 | 1.835e-17 | 3.61e-13 |
NPTN | 2.398e-17 | 4.72e-13 |
LOC400804 | 6.836e-17 | 1.35e-12 |
BTBD12 | 2.005e-16 | 3.95e-12 |
Figure S10. Get High-res Image As an example, this figure shows the association of OTOS to 'EXTRATHYROIDAL.EXTENSION'. P value = 2.55e-72 with ANOVA analysis.
![](V11ex.png)
Table S22. Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'
COMPLETENESS.OF.RESECTION | Labels | N |
R0 | 373 | |
R1 | 47 | |
R2 | 4 | |
RX | 29 | |
Significant markers | N = 14 |
Table S23. Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'
ANOVA_P | Q | |
---|---|---|
CAPN5__1 | 6.783e-15 | 1.34e-10 |
OMP | 6.783e-15 | 1.34e-10 |
ANKRD34B | 1.053e-12 | 2.07e-08 |
ASTN2 | 3.238e-12 | 6.38e-08 |
EPHA7 | 2.137e-11 | 4.21e-07 |
HS3ST2 | 2.281e-11 | 4.49e-07 |
KCNJ14 | 2.112e-10 | 4.16e-06 |
CCDC147 | 1.124e-09 | 2.21e-05 |
C17ORF108 | 6.456e-09 | 0.000127 |
MYL2 | 1.955e-08 | 0.000385 |
Figure S11. Get High-res Image As an example, this figure shows the association of CAPN5__1 to 'COMPLETENESS.OF.RESECTION'. P value = 6.78e-15 with ANOVA analysis.
![](V12ex.png)
Table S24. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'
NUMBER.OF.LYMPH.NODES | Mean (SD) | 3.55 (6.2) |
Significant markers | N = 1047 | |
pos. correlated | 24 | |
neg. correlated | 1023 |
Table S25. Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
FUT2 | -0.4349 | 3.792e-19 | 7.47e-15 |
TMEM173 | -0.4283 | 1.453e-18 | 2.86e-14 |
MET | -0.4263 | 2.202e-18 | 4.34e-14 |
TAGLN2 | -0.4188 | 9.723e-18 | 1.91e-13 |
MACF1 | -0.4175 | 1.262e-17 | 2.48e-13 |
CPNE1__1 | -0.4128 | 3.13e-17 | 6.16e-13 |
RBM12__1 | -0.4128 | 3.13e-17 | 6.16e-13 |
CAPN2 | -0.4118 | 3.792e-17 | 7.47e-13 |
HDAC9 | -0.4107 | 4.691e-17 | 9.24e-13 |
SMURF1 | -0.4085 | 7.142e-17 | 1.41e-12 |
Figure S12. Get High-res Image As an example, this figure shows the association of FUT2 to 'NUMBER.OF.LYMPH.NODES'. P value = 3.79e-19 with Spearman correlation analysis. The straight line presents the best linear regression.
![](V13ex.png)
Table S26. Basic characteristics of clinical feature: 'MULTIFOCALITY'
MULTIFOCALITY | Labels | N |
MULTIFOCAL | 219 | |
UNIFOCAL | 255 | |
Significant markers | N = 0 |
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Expresson data file = THCA-TP.meth.by_min_clin_corr.data.txt
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Clinical data file = THCA-TP.merged_data.txt
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Number of patients = 484
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Number of genes = 19697
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Number of clinical features = 15
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 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 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.
In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.