This pipeline computes the correlation between significantly recurrent gene mutations and selected clinical features.
Testing the association between mutation status of 11 genes and 17 clinical features across 395 patients, 10 significant findings detected with Q value < 0.25.
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BRAF mutation correlated to 'NEOPLASM.DISEASESTAGE', 'PATHOLOGY.T.STAGE', 'PATHOLOGY.N.STAGE', 'HISTOLOGICAL.TYPE', and 'EXTRATHYROIDAL.EXTENSION'.
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NRAS mutation correlated to 'PATHOLOGY.N.STAGE' and 'HISTOLOGICAL.TYPE'.
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DNMT3A mutation correlated to 'Time to Death'.
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ITGAL mutation correlated to 'NEOPLASM.DISEASESTAGE' and 'EXTRATHYROIDAL.EXTENSION'.
Clinical Features |
Time to Death |
AGE |
NEOPLASM DISEASESTAGE |
PATHOLOGY T STAGE |
PATHOLOGY N STAGE |
PATHOLOGY M STAGE |
GENDER |
HISTOLOGICAL TYPE |
RADIATIONS RADIATION REGIMENINDICATION |
RADIATIONEXPOSURE |
EXTRATHYROIDAL EXTENSION |
COMPLETENESS OF RESECTION |
NUMBER OF LYMPH NODES |
MULTIFOCALITY |
TUMOR SIZE |
RACE | ETHNICITY | ||
nMutated (%) | nWild-Type | logrank test | Wilcoxon-test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Wilcoxon-test | Fisher's exact test | Wilcoxon-test | Fisher's exact test | Fisher's exact test | |
BRAF | 237 (60%) | 158 |
0.912 (1.00) |
0.518 (1.00) |
0.00099 (0.17) |
0.00042 (0.0731) |
0.000205 (0.0359) |
0.116 (1.00) |
0.347 (1.00) |
1e-05 (0.00179) |
0.0322 (1.00) |
0.593 (1.00) |
1e-05 (0.00179) |
0.379 (1.00) |
0.00787 (1.00) |
0.835 (1.00) |
0.179 (1.00) |
0.887 (1.00) |
0.554 (1.00) |
NRAS | 34 (9%) | 361 |
0.463 (1.00) |
0.505 (1.00) |
0.0344 (1.00) |
0.161 (1.00) |
0.000142 (0.025) |
0.562 (1.00) |
0.84 (1.00) |
7e-05 (0.0124) |
0.61 (1.00) |
1 (1.00) |
0.19 (1.00) |
0.657 (1.00) |
0.00167 (0.284) |
0.369 (1.00) |
0.503 (1.00) |
0.0943 (1.00) |
0.0647 (1.00) |
ITGAL | 4 (1%) | 391 |
0.067 (1.00) |
0.0162 (1.00) |
0.00053 (0.0917) |
0.145 (1.00) |
0.347 (1.00) |
1 (1.00) |
0.0531 (1.00) |
0.708 (1.00) |
1 (1.00) |
1 (1.00) |
0.00142 (0.243) |
0.102 (1.00) |
0.626 (1.00) |
0.446 (1.00) |
1 (1.00) |
0.271 (1.00) |
|
DNMT3A | 3 (1%) | 392 |
0 (0) |
0.137 (1.00) |
0.0626 (1.00) |
0.167 (1.00) |
1 (1.00) |
1 (1.00) |
0.573 (1.00) |
0.656 (1.00) |
1 (1.00) |
0.125 (1.00) |
0.261 (1.00) |
0.424 (1.00) |
0.755 (1.00) |
1 (1.00) |
1 (1.00) |
1 (1.00) |
|
HRAS | 14 (4%) | 381 |
0.507 (1.00) |
0.313 (1.00) |
0.366 (1.00) |
0.377 (1.00) |
0.389 (1.00) |
0.26 (1.00) |
0.76 (1.00) |
0.0228 (1.00) |
1 (1.00) |
1 (1.00) |
0.69 (1.00) |
0.203 (1.00) |
0.762 (1.00) |
0.793 (1.00) |
0.725 (1.00) |
0.102 (1.00) |
0.617 (1.00) |
EIF1AX | 6 (2%) | 389 |
0.0942 (1.00) |
0.0573 (1.00) |
0.924 (1.00) |
1 (1.00) |
0.625 (1.00) |
0.475 (1.00) |
0.177 (1.00) |
0.0713 (1.00) |
1 (1.00) |
1 (1.00) |
1 (1.00) |
0.284 (1.00) |
0.491 (1.00) |
0.668 (1.00) |
0.472 (1.00) |
1 (1.00) |
|
NUP93 | 4 (1%) | 391 |
0.91 (1.00) |
0.522 (1.00) |
0.638 (1.00) |
0.734 (1.00) |
0.347 (1.00) |
0.657 (1.00) |
1 (1.00) |
0.0138 (1.00) |
1 (1.00) |
1 (1.00) |
1 (1.00) |
0.521 (1.00) |
0.365 (1.00) |
0.343 (1.00) |
1 (1.00) |
0.198 (1.00) |
1 (1.00) |
PPM1D | 5 (1%) | 390 |
0.923 (1.00) |
0.16 (1.00) |
0.241 (1.00) |
0.315 (1.00) |
1 (1.00) |
1 (1.00) |
0.606 (1.00) |
1 (1.00) |
1 (1.00) |
1 (1.00) |
0.114 (1.00) |
0.361 (1.00) |
1 (1.00) |
0.517 (1.00) |
1 (1.00) |
1 (1.00) |
|
KRAS | 4 (1%) | 391 |
0.873 (1.00) |
0.469 (1.00) |
1 (1.00) |
0.209 (1.00) |
0.625 (1.00) |
1 (1.00) |
0.576 (1.00) |
0.467 (1.00) |
1 (1.00) |
1 (1.00) |
1 (1.00) |
0.425 (1.00) |
0.313 (1.00) |
1 (1.00) |
0.74 (1.00) |
1 (1.00) |
|
DLC1 | 4 (1%) | 391 |
0.0772 (1.00) |
0.793 (1.00) |
0.737 (1.00) |
1 (1.00) |
0.604 (1.00) |
0.659 (1.00) |
1 (1.00) |
1 (1.00) |
1 (1.00) |
1 (1.00) |
0.389 (1.00) |
0.523 (1.00) |
0.405 (1.00) |
0.626 (1.00) |
0.573 (1.00) |
1 (1.00) |
0.271 (1.00) |
NLRP6 | 3 (1%) | 392 |
0.65 (1.00) |
0.418 (1.00) |
0.794 (1.00) |
0.168 (1.00) |
0.604 (1.00) |
0.134 (1.00) |
1 (1.00) |
0.657 (1.00) |
1 (1.00) |
1 (1.00) |
1 (1.00) |
1 (1.00) |
0.33 (1.00) |
0.6 (1.00) |
1 (1.00) |
P value = 0.00099 (Fisher's exact test), Q value = 0.17
nPatients | STAGE I | STAGE II | STAGE III | STAGE IV | STAGE IVA | STAGE IVC |
---|---|---|---|---|---|---|
ALL | 225 | 44 | 83 | 2 | 33 | 6 |
BRAF MUTATED | 129 | 18 | 59 | 0 | 26 | 4 |
BRAF WILD-TYPE | 96 | 26 | 24 | 2 | 7 | 2 |
P value = 0.00042 (Fisher's exact test), Q value = 0.073
nPatients | T1 | T2 | T3 | T4 |
---|---|---|---|---|
ALL | 115 | 137 | 126 | 15 |
BRAF MUTATED | 67 | 67 | 89 | 13 |
BRAF WILD-TYPE | 48 | 70 | 37 | 2 |
P value = 0.000205 (Fisher's exact test), Q value = 0.036
nPatients | 0 | 1 |
---|---|---|
ALL | 187 | 167 |
BRAF MUTATED | 97 | 119 |
BRAF WILD-TYPE | 90 | 48 |
P value = 1e-05 (Fisher's exact test), Q value = 0.0018
nPatients | OTHER SPECIFY | THYROID PAPILLARY CARCINOMA - CLASSICAL/USUAL | THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED) | THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES) |
---|---|---|---|---|
ALL | 6 | 277 | 83 | 29 |
BRAF MUTATED | 3 | 192 | 15 | 27 |
BRAF WILD-TYPE | 3 | 85 | 68 | 2 |
P value = 1e-05 (Fisher's exact test), Q value = 0.0018
nPatients | MINIMAL (T3) | MODERATE/ADVANCED (T4A) | NONE | VERY ADVANCED (T4B) |
---|---|---|---|---|
ALL | 102 | 11 | 267 | 1 |
BRAF MUTATED | 80 | 11 | 140 | 0 |
BRAF WILD-TYPE | 22 | 0 | 127 | 1 |
P value = 0.000142 (Fisher's exact test), Q value = 0.025
nPatients | 0 | 1 |
---|---|---|
ALL | 187 | 167 |
NRAS MUTATED | 27 | 5 |
NRAS WILD-TYPE | 160 | 162 |
P value = 7e-05 (Fisher's exact test), Q value = 0.012
nPatients | OTHER SPECIFY | THYROID PAPILLARY CARCINOMA - CLASSICAL/USUAL | THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED) | THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES) |
---|---|---|---|---|
ALL | 6 | 277 | 83 | 29 |
NRAS MUTATED | 0 | 15 | 19 | 0 |
NRAS WILD-TYPE | 6 | 262 | 64 | 29 |
P value = 0 (logrank test), Q value = 0
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 393 | 13 | 0.0 - 158.8 (16.1) |
DNMT3A MUTATED | 3 | 1 | 1.0 - 7.7 (6.8) |
DNMT3A WILD-TYPE | 390 | 12 | 0.0 - 158.8 (16.3) |
P value = 0.00053 (Fisher's exact test), Q value = 0.092
nPatients | STAGE I | STAGE II | STAGE III | STAGE IV | STAGE IVA | STAGE IVC |
---|---|---|---|---|---|---|
ALL | 225 | 44 | 83 | 2 | 33 | 6 |
ITGAL MUTATED | 0 | 1 | 0 | 1 | 2 | 0 |
ITGAL WILD-TYPE | 225 | 43 | 83 | 1 | 31 | 6 |
P value = 0.00142 (Fisher's exact test), Q value = 0.24
nPatients | MINIMAL (T3) | MODERATE/ADVANCED (T4A) | NONE | VERY ADVANCED (T4B) |
---|---|---|---|---|
ALL | 102 | 11 | 267 | 1 |
ITGAL MUTATED | 0 | 1 | 2 | 1 |
ITGAL WILD-TYPE | 102 | 10 | 265 | 0 |
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Mutation data file = transformed.cor.cli.txt
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Clinical data file = THCA-TP.merged_data.txt
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Number of patients = 395
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Number of significantly mutated genes = 11
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Number of selected clinical features = 17
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Exclude genes that fewer than K tumors have mutations, K = 3
For survival clinical features, the Kaplan-Meier survival curves of tumors with and without gene mutations were plotted and the statistical significance P values were estimated by logrank test (Bland and Altman 2004) using the 'survdiff' function in R
For binary or multi-class clinical features (nominal or ordinal), two-tailed Fisher's exact tests (Fisher 1922) were used to estimate the P values using the 'fisher.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.