Bladder Urothelial Carcinoma: Correlation between copy number variations of arm-level result and selected clinical features
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Overview
Introduction

This pipeline computes the correlation between significant arm-level copy number variations (cnvs) and selected clinical features.

Summary

Testing the association between copy number variation 73 arm-level results and 7 clinical features across 105 patients, 2 significant findings detected with Q value < 0.25.

  • 16q loss cnv correlated to 'TOBACCOSMOKINGHISTORYINDICATOR'.

  • 21q loss cnv correlated to 'AGE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 73 arm-level results and 7 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 2 significant findings detected.

Clinical
Features 		Time
to
Death 		AGE GENDER KARNOFSKY
PERFORMANCE
SCORE 		NUMBERPACKYEARSSMOKED STOPPEDSMOKINGYEAR TOBACCOSMOKINGHISTORYINDICATOR
nCNV (%) nWild-Type logrank test t-test Fisher's exact test t-test t-test t-test t-test
16q loss 13 (12%) 92 0.817
(1.00) 		0.455
(1.00) 		0.508
(1.00) 		0.288
(1.00) 		0.782
(1.00) 		0.236
(1.00) 		0.000516
(0.247)
21q loss 11 (10%) 94 0.593
(1.00) 		0.000393
(0.189) 		1
(1.00) 		0.00182
(0.868) 		0.823
(1.00) 		0.191
(1.00) 		0.72
(1.00)
1p gain 12 (11%) 93 0.134
(1.00) 		0.319
(1.00) 		1
(1.00) 		0.293
(1.00) 		0.539
(1.00) 		0.562
(1.00) 		0.179
(1.00)
1q gain 21 (20%) 84 0.0246
(1.00) 		0.0153
(1.00) 		1
(1.00) 		0.145
(1.00) 		0.684
(1.00) 		0.0998
(1.00) 		0.0246
(1.00)
2p gain 22 (21%) 83 0.347
(1.00) 		0.787
(1.00) 		0.000762
(0.365) 		0.35
(1.00) 		0.74
(1.00) 		0.0109
(1.00) 		0.625
(1.00)
2q gain 8 (8%) 97 0.593
(1.00) 		0.38
(1.00) 		0.682
(1.00) 		0.562
(1.00) 		0.456
(1.00) 		0.00232
(1.00) 		0.599
(1.00)
3p gain 22 (21%) 83 0.419
(1.00) 		0.697
(1.00) 		0.299
(1.00) 		0.581
(1.00) 		0.656
(1.00) 		0.794
(1.00) 		0.926
(1.00)
3q gain 30 (29%) 75 0.125
(1.00) 		0.0584
(1.00) 		0.229
(1.00) 		0.95
(1.00) 		0.677
(1.00) 		0.347
(1.00) 		0.88
(1.00)
4p gain 8 (8%) 97 0.0655
(1.00) 		0.899
(1.00) 		0.44
(1.00) 		0.272
(1.00) 		0.998
(1.00) 		0.639
(1.00)
4q gain 3 (3%) 102 0.288
(1.00) 		0.482
(1.00) 		1
(1.00) 		0.228
(1.00) 		0.915
(1.00)
5p gain 31 (30%) 74 0.627
(1.00) 		0.151
(1.00) 		0.633
(1.00) 		0.0478
(1.00) 		0.67
(1.00) 		0.501
(1.00) 		0.572
(1.00)
5q gain 14 (13%) 91 0.301
(1.00) 		0.256
(1.00) 		0.34
(1.00) 		0.306
(1.00) 		0.616
(1.00) 		0.538
(1.00) 		0.703
(1.00)
6p gain 6 (6%) 99 0.0841
(1.00) 		0.795
(1.00) 		0.667
(1.00) 		0.703
(1.00) 		0.587
(1.00) 		0.671
(1.00)
6q gain 4 (4%) 101 0.0887
(1.00) 		0.989
(1.00) 		0.574
(1.00) 		0.877
(1.00) 		0.961
(1.00) 		0.0714
(1.00)
7p gain 31 (30%) 74 0.376
(1.00) 		0.548
(1.00) 		0.485
(1.00) 		0.311
(1.00) 		0.768
(1.00) 		0.899
(1.00) 		0.21
(1.00)
7q gain 32 (30%) 73 0.705
(1.00) 		0.702
(1.00) 		0.0598
(1.00) 		0.312
(1.00) 		0.206
(1.00) 		0.755
(1.00) 		0.389
(1.00)
8p gain 14 (13%) 91 0.993
(1.00) 		0.213
(1.00) 		0.753
(1.00) 		0.745
(1.00) 		0.143
(1.00) 		0.0547
(1.00) 		0.139
(1.00)
8q gain 31 (30%) 74 0.544
(1.00) 		0.42
(1.00) 		1
(1.00) 		0.452
(1.00) 		0.366
(1.00) 		0.498
(1.00) 		0.831
(1.00)
9p gain 13 (12%) 92 0.022
(1.00) 		0.0308
(1.00) 		0.107
(1.00) 		0.907
(1.00) 		0.0531
(1.00) 		0.677
(1.00) 		0.102
(1.00)
9q gain 10 (10%) 95 0.0608
(1.00) 		0.141
(1.00) 		1
(1.00) 		0.745
(1.00) 		0.126
(1.00) 		0.434
(1.00) 		0.643
(1.00)
10p gain 22 (21%) 83 0.41
(1.00) 		0.883
(1.00) 		1
(1.00) 		0.62
(1.00) 		0.512
(1.00) 		0.43
(1.00) 		0.734
(1.00)
10q gain 6 (6%) 99 0.435
(1.00) 		0.224
(1.00) 		0.667
(1.00) 		0.383
(1.00) 		0.97
(1.00)
11p gain 5 (5%) 100 0.0941
(1.00) 		0.223
(1.00) 		0.319
(1.00) 		0.114
(1.00) 		0.53
(1.00) 		0.437
(1.00)
11q gain 6 (6%) 99 0.406
(1.00) 		0.483
(1.00) 		0.184
(1.00) 		0.745
(1.00) 		0.878
(1.00) 		0.907
(1.00)
12p gain 20 (19%) 85 0.82
(1.00) 		0.942
(1.00) 		1
(1.00) 		0.472
(1.00) 		0.761
(1.00) 		0.434
(1.00) 		0.621
(1.00)
12q gain 17 (16%) 88 0.262
(1.00) 		0.539
(1.00) 		0.144
(1.00) 		0.285
(1.00) 		0.741
(1.00) 		0.39
(1.00) 		0.931
(1.00)
13q gain 18 (17%) 87 0.38
(1.00) 		0.626
(1.00) 		1
(1.00) 		0.388
(1.00) 		0.282
(1.00) 		0.916
(1.00) 		0.783
(1.00)
14q gain 10 (10%) 95 0.592
(1.00) 		0.882
(1.00) 		0.458
(1.00) 		0.403
(1.00) 		0.279
(1.00) 		0.585
(1.00) 		0.408
(1.00)
15q gain 4 (4%) 101 0.113
(1.00) 		0.788
(1.00) 		1
(1.00) 		0.479
(1.00)
16p gain 9 (9%) 96 0.00125
(0.597) 		0.434
(1.00) 		0.257
(1.00) 		0.583
(1.00) 		0.206
(1.00) 		0.317
(1.00)
16q gain 11 (10%) 94 0.0285
(1.00) 		0.311
(1.00) 		0.0676
(1.00) 		0.446
(1.00) 		0.389
(1.00) 		0.873
(1.00) 		0.285
(1.00)
17p gain 8 (8%) 97 0.52
(1.00) 		0.967
(1.00) 		0.682
(1.00) 		0.778
(1.00) 		0.596
(1.00) 		0.998
(1.00)
17q gain 18 (17%) 87 0.616
(1.00) 		0.457
(1.00) 		0.57
(1.00) 		0.293
(1.00) 		0.469
(1.00) 		0.565
(1.00) 		0.377
(1.00)
18p gain 20 (19%) 85 0.728
(1.00) 		0.829
(1.00) 		0.416
(1.00) 		0.712
(1.00) 		0.261
(1.00) 		0.396
(1.00) 		0.129
(1.00)
18q gain 7 (7%) 98 0.0519
(1.00) 		0.863
(1.00) 		1
(1.00) 		0.681
(1.00) 		0.542
(1.00) 		0.219
(1.00)
19p gain 12 (11%) 93 0.872
(1.00) 		0.79
(1.00) 		1
(1.00) 		0.35
(1.00) 		0.493
(1.00) 		0.684
(1.00) 		0.747
(1.00)
19q gain 25 (24%) 80 0.173
(1.00) 		0.765
(1.00) 		0.613
(1.00) 		0.0639
(1.00) 		0.204
(1.00) 		0.528
(1.00) 		0.242
(1.00)
20p gain 42 (40%) 63 0.671
(1.00) 		0.733
(1.00) 		0.181
(1.00) 		0.734
(1.00) 		0.167
(1.00) 		0.291
(1.00) 		0.866
(1.00)
20q gain 43 (41%) 62 0.46
(1.00) 		0.626
(1.00) 		1
(1.00) 		0.603
(1.00) 		0.0771
(1.00) 		0.281
(1.00) 		0.106
(1.00)
21q gain 20 (19%) 85 0.315
(1.00) 		0.143
(1.00) 		0.786
(1.00) 		0.753
(1.00) 		0.372
(1.00) 		0.56
(1.00) 		0.914
(1.00)
22q gain 10 (10%) 95 0.0663
(1.00) 		0.483
(1.00) 		0.723
(1.00) 		0.712
(1.00) 		0.26
(1.00) 		0.0681
(1.00) 		0.0115
(1.00)
Xq gain 6 (6%) 99 0.6
(1.00) 		0.618
(1.00) 		0.667
(1.00) 		0.349
(1.00) 		0.504
(1.00)
2p loss 6 (6%) 99 0.652
(1.00) 		0.801
(1.00) 		1
(1.00) 		0.806
(1.00) 		0.244
(1.00) 		0.936
(1.00) 		0.425
(1.00)
2q loss 13 (12%) 92 0.0397
(1.00) 		0.712
(1.00) 		0.508
(1.00) 		0.806
(1.00) 		0.215
(1.00) 		0.89
(1.00) 		0.53
(1.00)
3p loss 7 (7%) 98 0.975
(1.00) 		0.667
(1.00) 		0.392
(1.00) 		0.0832
(1.00) 		0.89
(1.00) 		0.0132
(1.00)
4p loss 18 (17%) 87 0.542
(1.00) 		0.942
(1.00) 		0.57
(1.00) 		0.0381
(1.00) 		0.661
(1.00) 		0.864
(1.00) 		0.996
(1.00)
4q loss 17 (16%) 88 0.747
(1.00) 		0.632
(1.00) 		1
(1.00) 		0.0381
(1.00) 		0.785
(1.00) 		0.238
(1.00) 		0.915
(1.00)
5p loss 11 (10%) 94 0.312
(1.00) 		0.182
(1.00) 		0.172
(1.00) 		0.0019
(0.902) 		0.966
(1.00) 		0.2
(1.00) 		0.174
(1.00)
5q loss 25 (24%) 80 0.551
(1.00) 		0.449
(1.00) 		0.799
(1.00) 		0.534
(1.00) 		0.0707
(1.00) 		0.526
(1.00) 		0.114
(1.00)
6p loss 14 (13%) 91 0.984
(1.00) 		0.807
(1.00) 		0.525
(1.00) 		0.0019
(0.902) 		0.758
(1.00) 		0.896
(1.00) 		0.42
(1.00)
6q loss 23 (22%) 82 0.312
(1.00) 		0.663
(1.00) 		0.794
(1.00) 		0.00165
(0.785) 		0.199
(1.00) 		0.231
(1.00) 		0.0102
(1.00)
8p loss 34 (32%) 71 0.083
(1.00) 		0.969
(1.00) 		0.643
(1.00) 		0.232
(1.00) 		0.47
(1.00) 		0.248
(1.00) 		0.752
(1.00)
8q loss 4 (4%) 101 0.546
(1.00) 		0.125
(1.00) 		0.305
(1.00) 		0.87
(1.00) 		0.649
(1.00) 		0.852
(1.00)
9p loss 34 (32%) 71 0.754
(1.00) 		0.51
(1.00) 		0.162
(1.00) 		0.822
(1.00) 		0.377
(1.00) 		0.307
(1.00) 		0.302
(1.00)
9q loss 31 (30%) 74 0.651
(1.00) 		0.827
(1.00) 		0.1
(1.00) 		0.701
(1.00) 		0.178
(1.00) 		0.793
(1.00) 		0.318
(1.00)
10p loss 15 (14%) 90 0.547
(1.00) 		0.967
(1.00) 		1
(1.00) 		0.0381
(1.00) 		0.514
(1.00) 		0.808
(1.00) 		0.0361
(1.00)
10q loss 19 (18%) 86 0.533
(1.00) 		0.136
(1.00) 		1
(1.00) 		0.00182
(0.868) 		0.365
(1.00) 		0.875
(1.00) 		0.115
(1.00)
11p loss 35 (33%) 70 0.445
(1.00) 		0.21
(1.00) 		0.644
(1.00) 		0.0586
(1.00) 		0.737
(1.00) 		0.578
(1.00) 		0.713
(1.00)
11q loss 26 (25%) 79 0.843
(1.00) 		0.618
(1.00) 		1
(1.00) 		0.481
(1.00) 		0.254
(1.00) 		0.844
(1.00) 		0.736
(1.00)
12p loss 4 (4%) 101 0.975
(1.00) 		0.5
(1.00) 		0.574
(1.00) 		0.717
(1.00) 		0.0422
(1.00)
12q loss 6 (6%) 99 0.132
(1.00) 		0.351
(1.00) 		0.184
(1.00) 		0.988
(1.00) 		0.902
(1.00) 		0.34
(1.00)
13q loss 15 (14%) 90 0.794
(1.00) 		0.663
(1.00) 		0.227
(1.00) 		0.00198
(0.933) 		0.677
(1.00) 		0.461
(1.00) 		0.0155
(1.00)
14q loss 16 (15%) 89 0.228
(1.00) 		0.261
(1.00) 		0.547
(1.00) 		0.907
(1.00) 		0.0401
(1.00) 		0.0382
(1.00) 		0.759
(1.00)
15q loss 14 (13%) 91 0.191
(1.00) 		0.789
(1.00) 		0.525
(1.00) 		0.883
(1.00) 		0.754
(1.00) 		0.893
(1.00) 		0.252
(1.00)
16p loss 12 (11%) 93 0.382
(1.00) 		0.295
(1.00) 		0.172
(1.00) 		0.145
(1.00) 		0.581
(1.00) 		0.878
(1.00) 		0.0196
(1.00)
17p loss 32 (30%) 73 0.223
(1.00) 		0.721
(1.00) 		1
(1.00) 		0.439
(1.00) 		0.278
(1.00) 		0.722
(1.00) 		0.725
(1.00)
17q loss 4 (4%) 101 0.803
(1.00) 		0.588
(1.00) 		1
(1.00) 		0.663
(1.00)
18p loss 15 (14%) 90 0.113
(1.00) 		0.0591
(1.00) 		0.756
(1.00) 		0.668
(1.00) 		0.548
(1.00) 		0.251
(1.00) 		0.575
(1.00)
18q loss 29 (28%) 76 0.0178
(1.00) 		0.0663
(1.00) 		0.153
(1.00) 		0.79
(1.00) 		0.605
(1.00) 		0.127
(1.00) 		0.215
(1.00)
19p loss 7 (7%) 98 0.947
(1.00) 		0.781
(1.00) 		1
(1.00) 		0.304
(1.00) 		0.193
(1.00) 		0.483
(1.00)
19q loss 4 (4%) 101 0.345
(1.00) 		0.71
(1.00) 		0.574
(1.00) 		0.38
(1.00)
20p loss 4 (4%) 101 0.906
(1.00) 		0.221
(1.00) 		1
(1.00) 		0.0348
(1.00) 		0.102
(1.00) 		0.668
(1.00)
22q loss 22 (21%) 83 0.203
(1.00) 		0.894
(1.00) 		0.603
(1.00) 		0.298
(1.00) 		0.707
(1.00) 		0.883
(1.00) 		0.123
(1.00)
'16q loss mutation analysis' versus 'TOBACCOSMOKINGHISTORYINDICATOR'

P value = 0.000516 (t-test), Q value = 0.25

Table S1.  Gene #64: '16q loss mutation analysis' versus Clinical Feature #7: 'TOBACCOSMOKINGHISTORYINDICATOR'

nPatients Mean (Std.Dev)
ALL 99 2.6 (1.1)
16Q LOSS MUTATED 13 3.4 (0.7)
16Q LOSS WILD-TYPE 86 2.5 (1.2)

Figure S1.  Get High-res Image Gene #64: '16q loss mutation analysis' versus Clinical Feature #7: 'TOBACCOSMOKINGHISTORYINDICATOR'

'21q loss mutation analysis' versus 'AGE'

P value = 0.000393 (t-test), Q value = 0.19

Table S2.  Gene #72: '21q loss mutation analysis' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 104 66.9 (11.1)
21Q LOSS MUTATED 11 58.5 (6.2)
21Q LOSS WILD-TYPE 93 67.9 (11.2)

Figure S2.  Get High-res Image Gene #72: '21q loss mutation analysis' versus Clinical Feature #2: 'AGE'

Methods & Data
Input

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

  • Clinical data file = BLCA-TP.clin.merged.picked.txt

  • Number of patients = 105

  • Number of significantly arm-level cnvs = 73

  • Number of selected clinical features = 7

  • 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.

Download Results

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

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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