This pipeline computes the correlation between significantly recurrent gene mutations and selected clinical features.
Testing the association between mutation status of 6 genes and 15 clinical features across 394 patients, 8 significant findings detected with Q value < 0.25.
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NRAS mutation correlated to 'PATHOLOGY.N.STAGE', 'HISTOLOGICAL.TYPE', and 'NUMBER.OF.LYMPH.NODES'.
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BRAF mutation correlated to 'NEOPLASM.DISEASESTAGE', 'PATHOLOGY.T.STAGE', 'PATHOLOGY.N.STAGE', 'HISTOLOGICAL.TYPE', 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 |
||
nMutated (%) | nWild-Type | logrank test | t-test | Chi-square 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 | t-test | Fisher's exact test | t-test | |
BRAF | 237 (60%) | 157 |
0.912 (1.00) |
0.624 (1.00) |
0.00157 (0.129) |
0.00041 (0.0341) |
0.000295 (0.0248) |
0.106 (1.00) |
0.347 (1.00) |
2.2e-19 (1.95e-17) |
0.0323 (1.00) |
0.593 (1.00) |
2.42e-07 (2.13e-05) |
0.392 (1.00) |
0.542 (1.00) |
0.834 (1.00) |
0.37 (1.00) |
NRAS | 34 (9%) | 360 |
0.465 (1.00) |
0.444 (1.00) |
0.0471 (1.00) |
0.148 (1.00) |
0.000138 (0.0118) |
0.491 (1.00) |
1 (1.00) |
4.62e-05 (0.00402) |
0.611 (1.00) |
1 (1.00) |
0.189 (1.00) |
0.657 (1.00) |
5.53e-05 (0.00476) |
0.369 (1.00) |
0.65 (1.00) |
HRAS | 13 (3%) | 381 |
0.509 (1.00) |
0.592 (1.00) |
0.471 (1.00) |
0.436 (1.00) |
0.549 (1.00) |
0.285 (1.00) |
0.747 (1.00) |
0.0125 (1.00) |
1 (1.00) |
1 (1.00) |
0.691 (1.00) |
0.175 (1.00) |
0.513 (1.00) |
0.779 (1.00) |
0.955 (1.00) |
EIF1AX | 6 (2%) | 388 |
0.095 (1.00) |
0.138 (1.00) |
0.966 (1.00) |
1 (1.00) |
0.625 (1.00) |
0.473 (1.00) |
0.178 (1.00) |
0.0727 (1.00) |
1 (1.00) |
1 (1.00) |
1 (1.00) |
0.286 (1.00) |
0.772 (1.00) |
0.668 (1.00) |
0.691 (1.00) |
NUP93 | 4 (1%) | 390 |
0.91 (1.00) |
0.41 (1.00) |
0.777 (1.00) |
0.735 (1.00) |
0.348 (1.00) |
0.658 (1.00) |
1 (1.00) |
0.0145 (1.00) |
1 (1.00) |
1 (1.00) |
1 (1.00) |
0.522 (1.00) |
0.608 (1.00) |
0.344 (1.00) |
0.985 (1.00) |
NLRP6 | 3 (1%) | 391 |
0.65 (1.00) |
0.0327 (1.00) |
0.811 (1.00) |
0.169 (1.00) |
0.605 (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) |
0.524 (1.00) |
0.601 (1.00) |
P value = 0.000138 (Fisher's exact test), Q value = 0.012
nPatients | 0 | 1 |
---|---|---|
ALL | 186 | 167 |
NRAS MUTATED | 27 | 5 |
NRAS WILD-TYPE | 159 | 162 |
P value = 4.62e-05 (Fisher's exact test), Q value = 0.004
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 | 276 | 83 | 29 |
NRAS MUTATED | 0 | 15 | 19 | 0 |
NRAS WILD-TYPE | 6 | 261 | 64 | 29 |
P value = 5.53e-05 (t-test), Q value = 0.0048
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 308 | 3.3 (6.0) |
NRAS MUTATED | 26 | 0.9 (2.4) |
NRAS WILD-TYPE | 282 | 3.5 (6.2) |
P value = 0.00157 (Chi-square test), Q value = 0.13
nPatients | STAGE I | STAGE II | STAGE III | STAGE IV | STAGE IVA | STAGE IVC |
---|---|---|---|---|---|---|
ALL | 224 | 44 | 83 | 2 | 33 | 6 |
BRAF MUTATED | 129 | 18 | 59 | 0 | 26 | 4 |
BRAF WILD-TYPE | 95 | 26 | 24 | 2 | 7 | 2 |
P value = 0.00041 (Fisher's exact test), Q value = 0.034
nPatients | T1 | T2 | T3 | T4 |
---|---|---|---|---|
ALL | 115 | 135 | 127 | 15 |
BRAF MUTATED | 67 | 66 | 90 | 13 |
BRAF WILD-TYPE | 48 | 69 | 37 | 2 |
P value = 0.000295 (Fisher's exact test), Q value = 0.025
nPatients | 0 | 1 |
---|---|---|
ALL | 186 | 167 |
BRAF MUTATED | 97 | 119 |
BRAF WILD-TYPE | 89 | 48 |
P value = 2.2e-19 (Fisher's exact test), Q value = 2e-17
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 | 276 | 83 | 29 |
BRAF MUTATED | 3 | 192 | 15 | 27 |
BRAF WILD-TYPE | 3 | 84 | 68 | 2 |
P value = 2.42e-07 (Fisher's exact test), Q value = 2.1e-05
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 |
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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 = 394
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Number of significantly mutated genes = 6
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Number of selected clinical features = 15
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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 continuous numerical clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the clinical values between tumors with and without gene mutations using 't.test' function in R
For multi-class clinical features (nominal or ordinal), Chi-square tests (Greenwood and Nikulin 1996) were used to estimate the P values using the 'chisq.test' 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.