Correlation between gene mutation status and selected clinical features
Colon Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between gene mutation status and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C11Z4334
Overview
Introduction

This pipeline computes the correlation between significantly recurrent gene mutations and selected clinical features.

Summary

Testing the association between mutation status of 27 genes and 10 clinical features across 154 patients, one significant finding detected with Q value < 0.25.

  • BRAF mutation correlated to 'HISTOLOGICAL.TYPE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 27 genes and 10 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, one significant finding detected.

Clinical
Features
Time
to
Death
AGE NEOPLASM
DISEASESTAGE
PATHOLOGY
T
STAGE
PATHOLOGY
N
STAGE
PATHOLOGY
M
STAGE
GENDER HISTOLOGICAL
TYPE
COMPLETENESS
OF
RESECTION
NUMBER
OF
LYMPH
NODES
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 Wilcoxon-test
BRAF 20 (13%) 134 0.208
(1.00)
0.022
(1.00)
0.108
(1.00)
0.0623
(1.00)
0.799
(1.00)
0.398
(1.00)
0.0915
(1.00)
3.92e-05
(0.0106)
0.589
(1.00)
0.851
(1.00)
APC 107 (69%) 47 0.663
(1.00)
0.171
(1.00)
0.844
(1.00)
0.811
(1.00)
0.971
(1.00)
0.521
(1.00)
0.0138
(1.00)
0.62
(1.00)
0.162
(1.00)
0.831
(1.00)
TP53 73 (47%) 81 0.967
(1.00)
0.0654
(1.00)
0.236
(1.00)
0.622
(1.00)
0.313
(1.00)
0.555
(1.00)
0.519
(1.00)
0.00481
(1.00)
0.66
(1.00)
0.0769
(1.00)
KRAS 59 (38%) 95 0.601
(1.00)
0.00815
(1.00)
0.654
(1.00)
0.975
(1.00)
0.356
(1.00)
0.316
(1.00)
0.32
(1.00)
0.815
(1.00)
0.265
(1.00)
0.205
(1.00)
NRAS 15 (10%) 139 0.85
(1.00)
0.148
(1.00)
0.29
(1.00)
0.525
(1.00)
0.0777
(1.00)
0.497
(1.00)
0.0268
(1.00)
1
(1.00)
0.279
(1.00)
0.959
(1.00)
SMAD4 18 (12%) 136 0.141
(1.00)
0.576
(1.00)
0.901
(1.00)
0.911
(1.00)
0.83
(1.00)
1
(1.00)
0.803
(1.00)
0.299
(1.00)
0.771
(1.00)
0.503
(1.00)
FBXW7 29 (19%) 125 0.336
(1.00)
0.0194
(1.00)
0.0124
(1.00)
0.106
(1.00)
0.604
(1.00)
0.0177
(1.00)
0.216
(1.00)
0.0151
(1.00)
0.0804
(1.00)
0.402
(1.00)
SMAD2 10 (6%) 144 0.536
(1.00)
0.639
(1.00)
0.00166
(0.447)
0.412
(1.00)
0.67
(1.00)
0.636
(1.00)
0.327
(1.00)
0.16
(1.00)
0.407
(1.00)
0.378
(1.00)
FAM123B 19 (12%) 135 0.102
(1.00)
0.551
(1.00)
0.714
(1.00)
0.757
(1.00)
0.253
(1.00)
1
(1.00)
1
(1.00)
0.74
(1.00)
1
(1.00)
0.728
(1.00)
MGC42105 10 (6%) 144 0.577
(1.00)
0.817
(1.00)
0.209
(1.00)
0.28
(1.00)
0.477
(1.00)
0.399
(1.00)
0.746
(1.00)
0.639
(1.00)
1
(1.00)
0.176
(1.00)
ACVR1B 13 (8%) 141 0.595
(1.00)
0.733
(1.00)
0.298
(1.00)
0.0262
(1.00)
1
(1.00)
0.722
(1.00)
1
(1.00)
0.0236
(1.00)
1
(1.00)
0.826
(1.00)
DNMT1 12 (8%) 142 0.756
(1.00)
0.397
(1.00)
0.193
(1.00)
0.00748
(1.00)
0.102
(1.00)
1
(1.00)
0.368
(1.00)
0.0161
(1.00)
0.449
(1.00)
0.0661
(1.00)
PCBP1 4 (3%) 150 0.43
(1.00)
0.0201
(1.00)
0.109
(1.00)
0.326
(1.00)
0.641
(1.00)
0.0344
(1.00)
1
(1.00)
1
(1.00)
1
(1.00)
0.477
(1.00)
CDC27 10 (6%) 144 0.518
(1.00)
0.703
(1.00)
0.231
(1.00)
0.759
(1.00)
0.479
(1.00)
0.401
(1.00)
0.0979
(1.00)
1
(1.00)
0.443
(1.00)
0.133
(1.00)
PIK3CA 26 (17%) 128 0.485
(1.00)
0.279
(1.00)
0.0491
(1.00)
0.564
(1.00)
0.0102
(1.00)
0.335
(1.00)
0.83
(1.00)
0.217
(1.00)
0.445
(1.00)
0.00413
(1.00)
BCOR 6 (4%) 148 0.0576
(1.00)
0.306
(1.00)
0.033
(1.00)
0.0426
(1.00)
1
(1.00)
1
(1.00)
0.681
(1.00)
0.209
(1.00)
0.602
(1.00)
0.95
(1.00)
ZHX2 8 (5%) 146 0.212
(1.00)
0.58
(1.00)
0.0958
(1.00)
0.151
(1.00)
0.369
(1.00)
0.613
(1.00)
1
(1.00)
0.603
(1.00)
0.635
(1.00)
0.19
(1.00)
KLHL5 5 (3%) 149 0.438
(1.00)
0.308
(1.00)
0.012
(1.00)
0.153
(1.00)
1
(1.00)
1
(1.00)
1
(1.00)
0.548
(1.00)
1
(1.00)
0.982
(1.00)
CASP8 10 (6%) 144 0.74
(1.00)
0.0944
(1.00)
0.206
(1.00)
0.184
(1.00)
0.0985
(1.00)
0.404
(1.00)
1
(1.00)
0.16
(1.00)
0.445
(1.00)
0.0351
(1.00)
PCDHGB1 7 (5%) 147 0.16
(1.00)
0.407
(1.00)
0.0436
(1.00)
0.2
(1.00)
1
(1.00)
0.611
(1.00)
0.442
(1.00)
0.267
(1.00)
1
(1.00)
0.604
(1.00)
UBXN11 3 (2%) 151 0.417
(1.00)
0.406
(1.00)
0.118
(1.00)
0.036
(1.00)
1
(1.00)
1
(1.00)
1
(1.00)
0.00268
(0.719)
1
(1.00)
0.953
(1.00)
MIER3 10 (6%) 144 0.631
(1.00)
0.692
(1.00)
0.164
(1.00)
0.571
(1.00)
0.204
(1.00)
0.401
(1.00)
0.746
(1.00)
1
(1.00)
0.651
(1.00)
0.117
(1.00)
TBC1D10C 3 (2%) 151 0.529
(1.00)
0.444
(1.00)
0.327
(1.00)
0.711
(1.00)
0.135
(1.00)
1
(1.00)
1
(1.00)
0.055
(1.00)
1
(1.00)
0.606
(1.00)
TCF7L2 11 (7%) 143 0.196
(1.00)
0.231
(1.00)
0.396
(1.00)
0.568
(1.00)
1
(1.00)
1
(1.00)
0.533
(1.00)
0.368
(1.00)
1
(1.00)
0.716
(1.00)
PCDHGA9 5 (3%) 149 0.915
(1.00)
0.447
(1.00)
0.237
(1.00)
0.127
(1.00)
1
(1.00)
1
(1.00)
0.367
(1.00)
0.548
(1.00)
0.0816
(1.00)
0.982
(1.00)
PCDHGA7 5 (3%) 149 0.86
(1.00)
0.632
(1.00)
0.18
(1.00)
0.661
(1.00)
0.296
(1.00)
1
(1.00)
1
(1.00)
0.153
(1.00)
1
(1.00)
0.662
(1.00)
KLK2 3 (2%) 151 0.439
(1.00)
0.346
(1.00)
0.733
(1.00)
1
(1.00)
1
(1.00)
1
(1.00)
1
(1.00)
0.377
(1.00)
1
(1.00)
0.791
(1.00)
'BRAF MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 3.92e-05 (Fisher's exact test), Q value = 0.011

Table S1.  Gene #8: 'BRAF MUTATION STATUS' versus Clinical Feature #8: 'HISTOLOGICAL.TYPE'

nPatients COLON ADENOCARCINOMA COLON MUCINOUS ADENOCARCINOMA
ALL 130 22
BRAF MUTATED 10 10
BRAF WILD-TYPE 120 12

Figure S1.  Get High-res Image Gene #8: 'BRAF MUTATION STATUS' versus Clinical Feature #8: 'HISTOLOGICAL.TYPE'

Methods & Data
Input
  • Mutation data file = transformed.cor.cli.txt

  • Clinical data file = COAD-TP.merged_data.txt

  • Number of patients = 154

  • Number of significantly mutated genes = 27

  • Number of selected clinical features = 10

  • Exclude genes that fewer than K tumors have mutations, K = 3

Survival analysis

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

Fisher's exact test

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

Q value calculation

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.

Download Results

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.

References
[1] Bland and Altman, Statistics notes: The logrank test, BMJ 328(7447):1073 (2004)
[2] Fisher, R.A., On the interpretation of chi-square from contingency tables, and the calculation of P, Journal of the Royal Statistical Society 85(1):87-94 (1922)
[3] Benjamini and Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing, Journal of the Royal Statistical Society Series B 59:289-300 (1995)