This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.
Testing the association between 19705 genes and 17 clinical features across 497 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 14 clinical features related to at least one genes.
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25 genes correlated to 'Time to Death'.
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FAM118B__1 , SYNGR3 , KLHL29 , ANKRD53 , SYN2__1 , ...
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511 genes correlated to 'AGE'.
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MGA , INA , NHLRC1 , SYNGR3 , C1ORF59 , ...
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391 genes correlated to 'NEOPLASM.DISEASESTAGE'.
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MGA , INA , TBKBP1 , RANBP17 , IFT140 , ...
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288 genes correlated to 'PATHOLOGY.T.STAGE'.
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TBKBP1 , GJD3 , IFT140 , TMEM204 , PDGFB , ...
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1723 genes correlated to 'PATHOLOGY.N.STAGE'.
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BMP1 , DAGLA , ST6GALNAC5 , CPNE1__1 , RBM12__1 , ...
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3 genes correlated to 'PATHOLOGY.M.STAGE'.
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IQCD , TPCN1 , SLC25A37
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33 genes correlated to 'GENDER'.
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ALG11__2 , UTP14C__1 , ETF1 , KIF4B , FAM35A , ...
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3138 genes correlated to 'HISTOLOGICAL.TYPE'.
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LEPR , LEPROT , PON2 , GPR115 , XDH , ...
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9 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
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KLHDC1 , C1ORF77 , S100A13__1 , ZNF782 , PPOX , ...
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389 genes correlated to 'EXTRATHYROIDAL.EXTENSION'.
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NRCAM , TBKBP1 , PDGFB , IFT140 , TMEM204 , ...
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2 genes correlated to 'COMPLETENESS.OF.RESECTION'.
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SLC25A37 , NECAB2
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1299 genes correlated to 'NUMBER.OF.LYMPH.NODES'.
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FUT2 , MET , TMEM173 , MACF1 , TAGLN2 , ...
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1 gene correlated to 'TUMOR.SIZE'.
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TGFBR1
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49 genes correlated to 'RACE'.
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SCAMP5 , CDKN2AIP , CLTC , PTGES , RAD21L1 , ...
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No genes correlated to 'RADIATIONEXPOSURE', 'MULTIFOCALITY', and 'ETHNICITY'.
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=25 | shorter survival | N=18 | longer survival | N=7 |
AGE | Spearman correlation test | N=511 | older | N=505 | younger | N=6 |
NEOPLASM DISEASESTAGE | Kruskal-Wallis test | N=391 | ||||
PATHOLOGY T STAGE | Spearman correlation test | N=288 | higher stage | N=115 | lower stage | N=173 |
PATHOLOGY N STAGE | Wilcoxon test | N=1723 | class1 | N=1723 | class0 | N=0 |
PATHOLOGY M STAGE | Kruskal-Wallis test | N=3 | ||||
GENDER | Wilcoxon test | N=33 | male | N=33 | female | N=0 |
HISTOLOGICAL TYPE | Kruskal-Wallis test | N=3138 | ||||
RADIATIONS RADIATION REGIMENINDICATION | Wilcoxon test | N=9 | yes | N=9 | no | N=0 |
RADIATIONEXPOSURE | Wilcoxon test | N=0 | ||||
EXTRATHYROIDAL EXTENSION | Kruskal-Wallis test | N=389 | ||||
COMPLETENESS OF RESECTION | Kruskal-Wallis test | N=2 | ||||
NUMBER OF LYMPH NODES | Spearman correlation test | N=1299 | higher number.of.lymph.nodes | N=39 | lower number.of.lymph.nodes | N=1260 |
MULTIFOCALITY | Wilcoxon test | N=0 | ||||
TUMOR SIZE | Spearman correlation test | N=1 | higher tumor.size | N=1 | lower tumor.size | N=0 |
RACE | Kruskal-Wallis test | N=49 | ||||
ETHNICITY | Wilcoxon test | N=0 |
Time to Death | Duration (Months) | 0-158.8 (median=16.6) |
censored | N = 479 | |
death | N = 14 | |
Significant markers | N = 25 | |
associated with shorter survival | 18 | |
associated with longer survival | 7 |
HazardRatio | Wald_P | Q | C_index | |
---|---|---|---|---|
FAM118B__1 | 0 | 1.92e-07 | 0.0038 | 0.226 |
SYNGR3 | 211 | 2.675e-07 | 0.0053 | 0.75 |
KLHL29 | 0 | 3.491e-07 | 0.0069 | 0.223 |
ANKRD53 | 431 | 4.079e-07 | 0.008 | 0.649 |
SYN2__1 | 361 | 9.515e-07 | 0.019 | 0.854 |
RAB6C | 34001 | 9.687e-07 | 0.019 | 0.788 |
LOC150786 | 10001 | 1.305e-06 | 0.026 | 0.877 |
SLC6A17 | 840001 | 1.701e-06 | 0.034 | 0.837 |
ARSJ | 301 | 2.879e-06 | 0.057 | 0.77 |
GSG1L | 0 | 2.928e-06 | 0.058 | 0.216 |
AGE | Mean (SD) | 47.13 (16) |
Significant markers | N = 511 | |
pos. correlated | 505 | |
neg. correlated | 6 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
MGA | 0.5323 | 1.027e-37 | 2.02e-33 |
INA | 0.4867 | 6.305e-31 | 1.24e-26 |
NHLRC1 | 0.4847 | 1.205e-30 | 2.37e-26 |
SYNGR3 | 0.4685 | 1.769e-28 | 3.48e-24 |
C1ORF59 | 0.4679 | 2.115e-28 | 4.17e-24 |
RANBP17 | 0.4658 | 3.91e-28 | 7.7e-24 |
ACN9 | 0.4528 | 1.697e-26 | 3.34e-22 |
OTUD7A | 0.4424 | 3.096e-25 | 6.1e-21 |
ZNF518B | 0.4301 | 8.446e-24 | 1.66e-19 |
NTNG2 | 0.4296 | 9.733e-24 | 1.92e-19 |
NEOPLASM.DISEASESTAGE | Labels | N |
STAGE I | 281 | |
STAGE II | 52 | |
STAGE III | 109 | |
STAGE IV | 2 | |
STAGE IVA | 45 | |
STAGE IVC | 6 | |
Significant markers | N = 391 |
PATHOLOGY.T.STAGE | Mean (SD) | 2.13 (0.88) |
N | ||
1 | 141 | |
2 | 167 | |
3 | 165 | |
4 | 21 | |
Significant markers | N = 288 | |
pos. correlated | 115 | |
neg. correlated | 173 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
TBKBP1 | 0.3115 | 1.412e-12 | 2.78e-08 |
GJD3 | 0.2967 | 1.701e-11 | 3.35e-07 |
IFT140 | 0.2957 | 1.995e-11 | 3.93e-07 |
TMEM204 | 0.2957 | 1.995e-11 | 3.93e-07 |
PDGFB | 0.2854 | 1.04e-10 | 2.05e-06 |
GGT7 | 0.2759 | 4.406e-10 | 8.68e-06 |
PSD3 | -0.2689 | 1.258e-09 | 2.48e-05 |
BTBD3 | 0.2671 | 1.636e-09 | 3.22e-05 |
FLJ42875 | 0.2661 | 1.885e-09 | 3.71e-05 |
CKMT2 | 0.2648 | 2.266e-09 | 4.46e-05 |
PATHOLOGY.N.STAGE | Labels | N |
class0 | 225 | |
class1 | 222 | |
Significant markers | N = 1723 | |
Higher in class1 | 1723 | |
Higher in class0 | 0 |
W(pos if higher in 'class1') | wilcoxontestP | Q | AUC | |
---|---|---|---|---|
BMP1 | 13046 | 2.434e-18 | 4.8e-14 | 0.7388 |
DAGLA | 13061 | 2.682e-18 | 5.28e-14 | 0.7385 |
ST6GALNAC5 | 13073 | 2.898e-18 | 5.71e-14 | 0.7383 |
CPNE1__1 | 13184 | 5.92e-18 | 1.17e-13 | 0.7361 |
RBM12__1 | 13184 | 5.92e-18 | 1.17e-13 | 0.7361 |
SLC34A2 | 13232 | 8.046e-18 | 1.59e-13 | 0.7351 |
MET | 13236 | 8.254e-18 | 1.63e-13 | 0.735 |
PON2 | 13335 | 1.548e-17 | 3.05e-13 | 0.733 |
MACF1 | 13458 | 3.357e-17 | 6.61e-13 | 0.7306 |
CAPN2 | 13516 | 4.822e-17 | 9.5e-13 | 0.7294 |
PATHOLOGY.M.STAGE | Labels | N |
M0 | 274 | |
M1 | 9 | |
MX | 213 | |
Significant markers | N = 3 |
GENDER | Labels | N |
FEMALE | 365 | |
MALE | 132 | |
Significant markers | N = 33 | |
Higher in MALE | 33 | |
Higher in FEMALE | 0 |
W(pos if higher in 'MALE') | wilcoxontestP | Q | AUC | |
---|---|---|---|---|
ALG11__2 | 47962 | 6.111e-64 | 1.2e-59 | 0.9955 |
UTP14C__1 | 47962 | 6.111e-64 | 1.2e-59 | 0.9955 |
ETF1 | 47544 | 8.751e-62 | 1.72e-57 | 0.9868 |
KIF4B | 4554 | 2.055e-43 | 4.05e-39 | 0.9055 |
FAM35A | 7530 | 1.121e-31 | 2.21e-27 | 0.8437 |
GLUD1__1 | 7530 | 1.121e-31 | 2.21e-27 | 0.8437 |
MTFR1 | 40283 | 2.315e-30 | 4.56e-26 | 0.8361 |
WBP11P1 | 38801 | 2.396e-25 | 4.72e-21 | 0.8053 |
ANKRD20A4 | 35762 | 1.531e-16 | 3.01e-12 | 0.7423 |
DACH1 | 12597 | 4.382e-16 | 8.63e-12 | 0.7385 |
HISTOLOGICAL.TYPE | Labels | N |
OTHER SPECIFY | 9 | |
THYROID PAPILLARY CARCINOMA - CLASSICAL/USUAL | 353 | |
THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED) | 100 | |
THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES) | 35 | |
Significant markers | N = 3138 |
9 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N |
NO | 14 | |
YES | 483 | |
Significant markers | N = 9 | |
Higher in YES | 9 | |
Higher in NO | 0 |
W(pos if higher in 'YES') | wilcoxontestP | Q | AUC | |
---|---|---|---|---|
KLHDC1 | 906 | 2.995e-06 | 0.059 | 0.866 |
C1ORF77 | 981 | 5.91e-06 | 0.116 | 0.8549 |
S100A13__1 | 981 | 5.91e-06 | 0.116 | 0.8549 |
ZNF782 | 988 | 6.291e-06 | 0.124 | 0.8539 |
PPOX | 991 | 6.585e-06 | 0.13 | 0.8531 |
COPS8 | 1013 | 7.852e-06 | 0.155 | 0.8502 |
C13ORF23 | 1050 | 1.086e-05 | 0.214 | 0.8447 |
NHLRC3 | 1050 | 1.086e-05 | 0.214 | 0.8447 |
WBP4 | 1080 | 1.407e-05 | 0.277 | 0.8403 |
RADIATIONEXPOSURE | Labels | N |
NO | 418 | |
YES | 17 | |
Significant markers | N = 0 |
EXTRATHYROIDAL.EXTENSION | Labels | N |
MINIMAL (T3) | 130 | |
MODERATE/ADVANCED (T4A) | 16 | |
NONE | 330 | |
VERY ADVANCED (T4B) | 1 | |
Significant markers | N = 389 |
COMPLETENESS.OF.RESECTION | Labels | N |
R0 | 380 | |
R1 | 51 | |
R2 | 4 | |
RX | 30 | |
Significant markers | N = 2 |
NUMBER.OF.LYMPH.NODES | Mean (SD) | 3.56 (6.2) |
Significant markers | N = 1299 | |
pos. correlated | 39 | |
neg. correlated | 1260 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
FUT2 | -0.4216 | 2.508e-18 | 4.94e-14 |
MET | -0.4203 | 3.252e-18 | 6.41e-14 |
TMEM173 | -0.4127 | 1.476e-17 | 2.91e-13 |
MACF1 | -0.4048 | 6.87e-17 | 1.35e-12 |
TAGLN2 | -0.4 | 1.721e-16 | 3.39e-12 |
CAPN2 | -0.3988 | 2.126e-16 | 4.19e-12 |
CPNE1__1 | -0.3976 | 2.684e-16 | 5.29e-12 |
RBM12__1 | -0.3976 | 2.684e-16 | 5.29e-12 |
SMURF1 | -0.3963 | 3.417e-16 | 6.73e-12 |
DUSP6 | -0.3933 | 5.936e-16 | 1.17e-11 |
MULTIFOCALITY | Labels | N |
MULTIFOCAL | 225 | |
UNIFOCAL | 262 | |
Significant markers | N = 0 |
TUMOR.SIZE | Mean (SD) | 2.97 (1.6) |
Significant markers | N = 1 | |
pos. correlated | 1 | |
neg. correlated | 0 |
RACE | Labels | N |
AMERICAN INDIAN OR ALASKA NATIVE | 1 | |
ASIAN | 49 | |
BLACK OR AFRICAN AMERICAN | 26 | |
WHITE | 322 | |
Significant markers | N = 49 |
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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 = 497
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Number of genes = 19705
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Number of clinical features = 17
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.