Correlation between gene mutation status and selected clinical features
Overview
Introduction

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

Summary

Testing the association between mutation status of 89 genes and 8 clinical features across 293 patients, 3 significant findings detected with Q value < 0.25.

  • NUDT11 mutation correlated to 'AGE'.

  • FBXO43 mutation correlated to 'Time to Death'.

  • TMEM184C mutation correlated to 'AGE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 89 genes and 8 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 3 significant findings detected.

Clinical
Features 		Time
to
Death 		AGE GENDER KARNOFSKY
PERFORMANCE
SCORE 		PATHOLOGY
T 		PATHOLOGY
N 		PATHOLOGICSPREAD(M) NEOADJUVANT
THERAPY
nMutated (%) nWild-Type logrank test t-test Fisher's exact test t-test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test
NUDT11 3 (1%) 290 0.6
(1.00) 		1.58e-24
(9.73e-22) 		0.554
(1.00) 		0.718
(1.00) 		1
(1.00) 		1
(1.00)
FBXO43 5 (2%) 288 1.27e-13
(7.83e-11) 		0.621
(1.00) 		1
(1.00) 		0.446
(1.00) 		1
(1.00) 		0.513
(1.00) 		1
(1.00)
TMEM184C 4 (1%) 289 0.0172
(1.00) 		0.000391
(0.24) 		1
(1.00) 		0.796
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
VHL 145 (49%) 148 0.913
(1.00) 		0.0211
(1.00) 		0.113
(1.00) 		0.359
(1.00) 		0.498
(1.00) 		0.76
(1.00) 		0.732
(1.00) 		1
(1.00)
KDM5C 18 (6%) 275 0.0803
(1.00) 		0.206
(1.00) 		0.00486
(1.00) 		0.622
(1.00) 		0.516
(1.00) 		1
(1.00) 		1
(1.00)
PBRM1 110 (38%) 183 0.439
(1.00) 		0.987
(1.00) 		0.129
(1.00) 		0.429
(1.00) 		0.613
(1.00) 		1
(1.00) 		0.478
(1.00) 		0.559
(1.00)
RRAD 4 (1%) 289 0.0836
(1.00) 		0.806
(1.00) 		0.123
(1.00) 		0.0613
(1.00) 		0.211
(1.00) 		0.437
(1.00) 		1
(1.00)
SV2C 3 (1%) 290 0.731
(1.00) 		0.0205
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
TOR1A 3 (1%) 290 0.0532
(1.00) 		0.704
(1.00) 		1
(1.00) 		1
(1.00) 		0.0753
(1.00) 		1
(1.00) 		1
(1.00)
SETD2 35 (12%) 258 0.852
(1.00) 		0.123
(1.00) 		0.132
(1.00) 		0.101
(1.00) 		0.61
(1.00) 		0.0317
(1.00) 		0.318
(1.00)
PTEN 15 (5%) 278 0.87
(1.00) 		0.104
(1.00) 		1
(1.00) 		0.489
(1.00) 		0.0657
(1.00) 		1
(1.00) 		0.146
(1.00)
BAP1 28 (10%) 265 0.0144
(1.00) 		0.695
(1.00) 		0.00345
(1.00) 		0.00203
(1.00) 		0.637
(1.00) 		0.00126
(0.771) 		0.261
(1.00)
PIK3CA 14 (5%) 279 0.797
(1.00) 		0.387
(1.00) 		0.57
(1.00) 		0.152
(1.00) 		0.555
(1.00) 		1
(1.00) 		1
(1.00)
MTOR 24 (8%) 269 0.123
(1.00) 		0.203
(1.00) 		0.119
(1.00) 		0.298
(1.00) 		0.0602
(1.00) 		1
(1.00) 		1
(1.00)
STAG3L2 6 (2%) 287 0.252
(1.00) 		0.115
(1.00) 		1
(1.00) 		0.415
(1.00) 		1
(1.00) 		0.579
(1.00) 		1
(1.00)
EBPL 6 (2%) 287 0.48
(1.00) 		0.527
(1.00) 		0.00161
(0.987) 		0.117
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
KANK3 6 (2%) 287 0.733
(1.00) 		0.513
(1.00) 		1
(1.00) 		0.51
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
ZCCHC3 3 (1%) 290 0.392
(1.00) 		0.829
(1.00) 		0.554
(1.00) 		0.374
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
FAM174B 3 (1%) 290 0.476
(1.00) 		0.668
(1.00) 		1
(1.00) 		0.0917
(1.00) 		1
(1.00) 		1
(1.00)
ANKRD36 10 (3%) 283 0.284
(1.00) 		0.339
(1.00) 		1
(1.00) 		0.391
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
TSPAN19 4 (1%) 289 0.319
(1.00) 		0.467
(1.00) 		1
(1.00) 		0.458
(1.00) 		1
(1.00) 		0.437
(1.00) 		1
(1.00)
DACH2 7 (2%) 286 0.972
(1.00) 		0.7
(1.00) 		0.242
(1.00) 		1
(1.00) 		0.328
(1.00) 		0.236
(1.00) 		0.0702
(1.00)
KRTAP1-1 3 (1%) 290 0.296
(1.00) 		0.97
(1.00) 		0.0414
(1.00) 		0.0917
(1.00) 		0.35
(1.00) 		1
(1.00)
UQCRFS1 3 (1%) 290 0.321
(1.00) 		0.518
(1.00) 		0.278
(1.00) 		0.0452
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
CR1 11 (4%) 282 0.582
(1.00) 		0.936
(1.00) 		0.523
(1.00) 		0.831
(1.00) 		1
(1.00) 		0.645
(1.00) 		1
(1.00)
VCX2 3 (1%) 290 0.293
(1.00) 		0.058
(1.00) 		1
(1.00) 		0.143
(1.00) 		1
(1.00) 		0.35
(1.00) 		1
(1.00)
KRT1 5 (2%) 288 0.00506
(1.00) 		0.0322
(1.00) 		0.346
(1.00) 		0.172
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
ABCB1 8 (3%) 285 0.116
(1.00) 		0.582
(1.00) 		0.718
(1.00) 		0.882
(1.00) 		1
(1.00) 		0.603
(1.00) 		1
(1.00)
MADCAM1 4 (1%) 289 0.357
(1.00) 		0.751
(1.00) 		0.123
(1.00) 		0.0204
(1.00) 		1
(1.00) 		0.0871
(1.00) 		1
(1.00)
POLDIP2 4 (1%) 289 0.458
(1.00) 		0.705
(1.00) 		1
(1.00) 		0.458
(1.00) 		1
(1.00) 		0.437
(1.00) 		1
(1.00)
PCDHGA8 4 (1%) 289 0.251
(1.00) 		0.207
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
WDR52 9 (3%) 284 0.967
(1.00) 		0.395
(1.00) 		0.724
(1.00) 		0.647
(1.00) 		1
(1.00) 		0.342
(1.00) 		1
(1.00)
DNAH9 18 (6%) 275 0.857
(1.00) 		0.998
(1.00) 		0.445
(1.00) 		0.456
(1.00) 		0.792
(1.00) 		0.166
(1.00) 		0.484
(1.00) 		1
(1.00)
TPTE2 7 (2%) 286 0.3
(1.00) 		0.309
(1.00) 		1
(1.00) 		0.48
(1.00) 		1
(1.00) 		0.599
(1.00) 		1
(1.00)
CCNB2 5 (2%) 288 0.784
(1.00) 		0.459
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
OR5H1 4 (1%) 289 0.919
(1.00) 		0.524
(1.00) 		0.612
(1.00) 		0.606
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
NFE2L2 5 (2%) 288 0.163
(1.00) 		0.162
(1.00) 		1
(1.00) 		0.827
(1.00) 		1
(1.00) 		0.513
(1.00) 		1
(1.00)
GFRAL 5 (2%) 288 0.655
(1.00) 		0.0399
(1.00) 		1
(1.00) 		0.096
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
MSN 4 (1%) 289 0.63
(1.00) 		0.578
(1.00) 		1
(1.00) 		0.19
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
RECQL5 6 (2%) 287 0.0507
(1.00) 		0.575
(1.00) 		0.188
(1.00) 		0.607
(1.00) 		0.328
(1.00) 		0.183
(1.00) 		1
(1.00)
NPNT 6 (2%) 287 0.0806
(1.00) 		0.222
(1.00) 		0.668
(1.00) 		0.342
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
SCAI 7 (2%) 286 0.461
(1.00) 		0.583
(1.00) 		0.428
(1.00) 		0.246
(1.00) 		1
(1.00) 		0.599
(1.00) 		1
(1.00)
BAGE2 4 (1%) 289 0.961
(1.00) 		0.667
(1.00) 		0.612
(1.00) 		0.796
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
CNTNAP4 9 (3%) 284 0.485
(1.00) 		0.5
(1.00) 		0.724
(1.00) 		0.51
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
ZNF800 6 (2%) 287 0.166
(1.00) 		0.599
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.579
(1.00) 		1
(1.00)
SP8 3 (1%) 290 0.252
(1.00) 		0.0518
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
UGT2A3 4 (1%) 289 0.529
(1.00) 		0.354
(1.00) 		0.612
(1.00) 		1
(1.00) 		1
(1.00) 		0.0871
(1.00) 		1
(1.00)
LPAR4 4 (1%) 289 0.534
(1.00) 		0.457
(1.00) 		0.612
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
SFRS15 9 (3%) 284 0.564
(1.00) 		0.804
(1.00) 		0.724
(1.00) 		0.647
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
SPAM1 5 (2%) 288 0.27
(1.00) 		0.192
(1.00) 		0.661
(1.00) 		0.096
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
MED12L 8 (3%) 285 0.018
(1.00) 		0.875
(1.00) 		1
(1.00) 		0.882
(1.00) 		1
(1.00) 		0.289
(1.00) 		1
(1.00)
PRB4 3 (1%) 290 0.71
(1.00) 		0.0414
(1.00) 		0.519
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
WASL 5 (2%) 288 0.612
(1.00) 		0.225
(1.00) 		0.346
(1.00) 		0.325
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
RNF115 4 (1%) 289 0.611
(1.00) 		0.727
(1.00) 		0.612
(1.00) 		0.796
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
NF2 6 (2%) 287 0.424
(1.00) 		0.853
(1.00) 		0.423
(1.00) 		0.177
(1.00) 		0.271
(1.00) 		0.579
(1.00) 		1
(1.00)
SERPINB5 3 (1%) 290 0.764
(1.00) 		0.765
(1.00) 		0.554
(1.00) 		0.374
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
TP53 9 (3%) 284 0.0454
(1.00) 		0.091
(1.00) 		0.285
(1.00) 		0.032
(1.00) 		0.328
(1.00) 		1
(1.00) 		1
(1.00)
PRB3 3 (1%) 290 0.123
(1.00) 		0.554
(1.00) 		1
(1.00) 		0.0753
(1.00) 		1
(1.00) 		1
(1.00)
COL11A1 8 (3%) 285 0.946
(1.00) 		0.546
(1.00) 		0.269
(1.00) 		0.783
(1.00) 		0.271
(1.00) 		0.603
(1.00) 		1
(1.00)
KCNH7 8 (3%) 285 0.787
(1.00) 		0.95
(1.00) 		1
(1.00) 		0.529
(1.00) 		0.211
(1.00) 		0.603
(1.00) 		1
(1.00)
LMO4 3 (1%) 290 0.902
(1.00) 		0.0752
(1.00) 		1
(1.00) 		0.519
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
PCLO 20 (7%) 273 0.537
(1.00) 		0.775
(1.00) 		0.223
(1.00) 		0.763
(1.00) 		1
(1.00) 		0.737
(1.00) 		1
(1.00)
PRIM2 5 (2%) 288 0.105
(1.00) 		0.796
(1.00) 		0.346
(1.00) 		0.096
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
PTPN18 4 (1%) 289 0.416
(1.00) 		0.349
(1.00) 		1
(1.00) 		0.258
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
RPUSD2 3 (1%) 290 0.789
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
SLC2A14 3 (1%) 290 0.713
(1.00) 		0.897
(1.00) 		1
(1.00) 		0.519
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
ZKSCAN1 4 (1%) 289 0.558
(1.00) 		0.675
(1.00) 		0.612
(1.00) 		0.19
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
ZYG11B 6 (2%) 287 0.317
(1.00) 		0.00367
(1.00) 		1
(1.00) 		0.863
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
NBPF10 20 (7%) 273 0.237
(1.00) 		0.321
(1.00) 		0.151
(1.00) 		0.202
(1.00) 		0.139
(1.00) 		0.0353
(1.00) 		1
(1.00)
ADCY8 5 (2%) 288 0.706
(1.00) 		0.582
(1.00) 		0.167
(1.00) 		0.262
(1.00) 		0.0753
(1.00) 		0.513
(1.00) 		1
(1.00)
C5ORF13 3 (1%) 290 0.32
(1.00) 		0.465
(1.00) 		0.278
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
OR10G7 5 (2%) 288 0.0498
(1.00) 		0.301
(1.00) 		1
(1.00) 		0.568
(1.00) 		1
(1.00) 		0.513
(1.00) 		1
(1.00)
ADAMTS20 7 (2%) 286 0.163
(1.00) 		0.243
(1.00) 		0.698
(1.00) 		0.878
(1.00) 		1
(1.00) 		0.0523
(1.00) 		1
(1.00)
DPP10 6 (2%) 287 0.369
(1.00) 		0.902
(1.00) 		1
(1.00) 		0.225
(1.00) 		1
(1.00) 		0.183
(1.00) 		1
(1.00)
KRTAP4-1 3 (1%) 290 0.927
(1.00) 		0.173
(1.00) 		0.0414
(1.00) 		0.718
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
MYO6 3 (1%) 290 0.196
(1.00) 		0.554
(1.00) 		0.374
(1.00) 		1
(1.00) 		1
(1.00)
POTEC 10 (3%) 283 0.386
(1.00) 		0.0352
(1.00) 		1
(1.00) 		0.81
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
GRIN2B 10 (3%) 283 0.873
(1.00) 		0.48
(1.00) 		0.743
(1.00) 		0.902
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
MAGEC1 7 (2%) 286 0.586
(1.00) 		0.194
(1.00) 		0.242
(1.00) 		0.878
(1.00) 		0.328
(1.00) 		0.599
(1.00) 		1
(1.00)
LILRB3 3 (1%) 290 0.803
(1.00) 		0.92
(1.00) 		0.278
(1.00) 		0.244
(1.00) 		0.35
(1.00) 		1
(1.00)
C15ORF26 4 (1%) 289 0.221
(1.00) 		0.0652
(1.00) 		0.302
(1.00) 		0.458
(1.00) 		0.0871
(1.00) 		1
(1.00)
MARCKS 3 (1%) 290 0.298
(1.00) 		0.113
(1.00) 		0.278
(1.00) 		0.0917
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
MSR1 5 (2%) 288 0.156
(1.00) 		0.353
(1.00) 		1
(1.00) 		0.325
(1.00) 		0.0286
(1.00) 		0.513
(1.00) 		1
(1.00)
RALGAPA1 7 (2%) 286 0.909
(1.00) 		0.71
(1.00) 		0.428
(1.00) 		0.0809
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
CLYBL 4 (1%) 289 0.375
(1.00) 		0.646
(1.00) 		0.302
(1.00) 		0.124
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
SDR16C5 4 (1%) 289 0.825
(1.00) 		0.323
(1.00) 		0.302
(1.00) 		1
(1.00) 		1
(1.00) 		0.0871
(1.00) 		1
(1.00)
SPRYD5 4 (1%) 289 0.516
(1.00) 		0.454
(1.00) 		1
(1.00) 		0.606
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
RARA 4 (1%) 289 0.462
(1.00) 		0.554
(1.00) 		1
(1.00) 		0.606
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
STAG2 10 (3%) 283 0.951
(1.00) 		0.00867
(1.00) 		1
(1.00) 		0.0727
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
'NUDT11 MUTATION STATUS' versus 'AGE'

P value = 1.58e-24 (t-test), Q value = 9.7e-22

Table S1.  Gene #15: 'NUDT11 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 293 60.3 (11.9)
NUDT11 MUTATED 3 74.7 (0.6)
NUDT11 WILD-TYPE 290 60.2 (11.9)

Figure S1.  Get High-res Image Gene #15: 'NUDT11 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'FBXO43 MUTATION STATUS' versus 'Time to Death'

P value = 1.27e-13 (logrank test), Q value = 7.8e-11

Table S2.  Gene #69: 'FBXO43 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 291 77 0.1 - 109.6 (34.3)
FBXO43 MUTATED 5 3 1.6 - 10.8 (1.8)
FBXO43 WILD-TYPE 286 74 0.1 - 109.6 (34.9)

Figure S2.  Get High-res Image Gene #69: 'FBXO43 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'TMEM184C MUTATION STATUS' versus 'AGE'

P value = 0.000391 (t-test), Q value = 0.24

Table S3.  Gene #81: 'TMEM184C MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 293 60.3 (11.9)
TMEM184C MUTATED 4 79.8 (3.4)
TMEM184C WILD-TYPE 289 60.1 (11.8)

Figure S3.  Get High-res Image Gene #81: 'TMEM184C MUTATION STATUS' versus Clinical Feature #2: 'AGE'

Methods & Data
Input

  • Mutation data file = KIRC.mutsig.cluster.txt

  • Clinical data file = KIRC.clin.merged.picked.txt

  • Number of patients = 293

  • Number of significantly mutated genes = 89

  • Number of selected clinical features = 8

  • 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

Student's t-test analysis

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

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.

References
[1] Bland and Altman, Statistics notes: The logrank test, BMJ 328(7447):1073 (2004)
[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[3] 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)
[4] 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)
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