Bladder Urothelial Carcinoma: Correlation between copy number variations of arm-level result and selected clinical features
Maintained by TCGA GDAC Team (Broad Institute/Dana-Farber Cancer Institute/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 59 arm-level results and 4 clinical features across 53 patients, one significant finding detected with Q value < 0.25.

  • 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 59 arm-level results and 4 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 GENDER KARNOFSKY
PERFORMANCE
SCORE
nCNV (%) nWild-Type logrank test t-test Fisher's exact test t-test
21q loss 5 (9%) 48 0.814
(1.00)
1.75e-05
(0.00336)
0.638
(1.00)
1p gain 6 (11%) 47 0.0397
(1.00)
0.577
(1.00)
0.0709
(1.00)
1q gain 10 (19%) 43 0.139
(1.00)
0.397
(1.00)
0.287
(1.00)
2p gain 15 (28%) 38 0.451
(1.00)
0.956
(1.00)
0.0302
(1.00)
2q gain 6 (11%) 47 0.687
(1.00)
0.38
(1.00)
0.219
(1.00)
3p gain 12 (23%) 41 0.322
(1.00)
0.974
(1.00)
1
(1.00)
3q gain 15 (28%) 38 0.0693
(1.00)
0.477
(1.00)
0.357
(1.00)
0.445
(1.00)
4p gain 6 (11%) 47 0.473
(1.00)
0.799
(1.00)
1
(1.00)
5p gain 15 (28%) 38 0.478
(1.00)
0.921
(1.00)
0.357
(1.00)
0.68
(1.00)
5q gain 7 (13%) 46 0.299
(1.00)
0.363
(1.00)
0.686
(1.00)
6p gain 7 (13%) 46 0.464
(1.00)
0.665
(1.00)
1
(1.00)
7p gain 14 (26%) 39 0.791
(1.00)
0.189
(1.00)
1
(1.00)
7q gain 13 (25%) 40 0.808
(1.00)
0.489
(1.00)
0.753
(1.00)
8p gain 10 (19%) 43 0.71
(1.00)
0.544
(1.00)
0.494
(1.00)
8q gain 21 (40%) 32 0.697
(1.00)
0.221
(1.00)
0.779
(1.00)
0.68
(1.00)
9p gain 8 (15%) 45 0.0277
(1.00)
0.221
(1.00)
1
(1.00)
9q gain 8 (15%) 45 0.013
(1.00)
0.0822
(1.00)
0.253
(1.00)
10p gain 13 (25%) 40 0.676
(1.00)
0.252
(1.00)
0.52
(1.00)
10q gain 4 (8%) 49 0.533
(1.00)
0.348
(1.00)
1
(1.00)
12p gain 6 (11%) 47 0.962
(1.00)
0.953
(1.00)
1
(1.00)
12q gain 7 (13%) 46 0.964
(1.00)
0.654
(1.00)
0.686
(1.00)
13q gain 8 (15%) 45 0.926
(1.00)
0.579
(1.00)
1
(1.00)
0.445
(1.00)
14q gain 5 (9%) 48 0.853
(1.00)
0.51
(1.00)
1
(1.00)
16p gain 4 (8%) 49 0.0325
(1.00)
0.689
(1.00)
0.025
(1.00)
16q gain 8 (15%) 45 0.0811
(1.00)
0.599
(1.00)
0.0544
(1.00)
17p gain 4 (8%) 49 0.478
(1.00)
0.988
(1.00)
1
(1.00)
17q gain 11 (21%) 42 0.431
(1.00)
0.414
(1.00)
1
(1.00)
18p gain 6 (11%) 47 0.458
(1.00)
0.178
(1.00)
0.219
(1.00)
18q gain 3 (6%) 50 0.076
(1.00)
0.825
(1.00)
0.563
(1.00)
19p gain 4 (8%) 49 0.918
(1.00)
0.0851
(1.00)
0.295
(1.00)
19q gain 13 (25%) 40 0.0927
(1.00)
0.612
(1.00)
0.345
(1.00)
0.445
(1.00)
20p gain 15 (28%) 38 0.776
(1.00)
0.276
(1.00)
0.124
(1.00)
20q gain 18 (34%) 35 0.618
(1.00)
0.485
(1.00)
0.155
(1.00)
21q gain 13 (25%) 40 0.237
(1.00)
0.164
(1.00)
1
(1.00)
0.68
(1.00)
22q gain 4 (8%) 49 0.0748
(1.00)
0.408
(1.00)
0.633
(1.00)
2q loss 7 (13%) 46 0.748
(1.00)
0.635
(1.00)
0.431
(1.00)
0.886
(1.00)
3p loss 5 (9%) 48 0.819
(1.00)
0.123
(1.00)
1
(1.00)
4p loss 9 (17%) 44 0.478
(1.00)
0.408
(1.00)
0.14
(1.00)
4q loss 10 (19%) 43 0.46
(1.00)
0.743
(1.00)
0.724
(1.00)
5p loss 3 (6%) 50 0.158
(1.00)
0.688
(1.00)
0.0657
(1.00)
5q loss 11 (21%) 42 0.251
(1.00)
0.353
(1.00)
0.168
(1.00)
0.68
(1.00)
6p loss 6 (11%) 47 0.947
(1.00)
0.0354
(1.00)
0.683
(1.00)
6q loss 10 (19%) 43 0.0829
(1.00)
0.978
(1.00)
0.724
(1.00)
8p loss 12 (23%) 41 0.309
(1.00)
0.0495
(1.00)
1
(1.00)
9p loss 18 (34%) 35 0.83
(1.00)
0.747
(1.00)
0.557
(1.00)
0.912
(1.00)
9q loss 15 (28%) 38 0.746
(1.00)
0.427
(1.00)
0.065
(1.00)
0.616
(1.00)
10p loss 8 (15%) 45 0.204
(1.00)
0.991
(1.00)
0.253
(1.00)
10q loss 8 (15%) 45 0.242
(1.00)
0.526
(1.00)
0.705
(1.00)
11p loss 23 (43%) 30 0.715
(1.00)
0.776
(1.00)
0.415
(1.00)
0.109
(1.00)
11q loss 13 (25%) 40 0.731
(1.00)
0.429
(1.00)
0.52
(1.00)
0.261
(1.00)
13q loss 9 (17%) 44 0.805
(1.00)
0.636
(1.00)
0.72
(1.00)
14q loss 11 (21%) 42 0.84
(1.00)
0.718
(1.00)
0.327
(1.00)
15q loss 9 (17%) 44 0.222
(1.00)
0.521
(1.00)
0.464
(1.00)
0.636
(1.00)
16p loss 8 (15%) 45 0.122
(1.00)
0.938
(1.00)
0.445
(1.00)
16q loss 3 (6%) 50 0.647
(1.00)
0.516
(1.00)
1
(1.00)
17p loss 18 (34%) 35 0.0275
(1.00)
0.115
(1.00)
0.777
(1.00)
0.557
(1.00)
18p loss 6 (11%) 47 0.198
(1.00)
0.781
(1.00)
0.219
(1.00)
18q loss 16 (30%) 37 0.00271
(0.518)
0.54
(1.00)
0.225
(1.00)
0.445
(1.00)
22q loss 9 (17%) 44 0.295
(1.00)
0.212
(1.00)
0.464
(1.00)
'21q loss mutation analysis' versus 'AGE'

P value = 1.75e-05 (t-test), Q value = 0.0034

Table S1.  Gene #58: '21q loss mutation analysis' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 53 68.6 (10.1)
21Q LOSS MUTATED 5 58.8 (2.8)
21Q LOSS WILD-TYPE 48 69.6 (10.1)

Figure S1.  Get High-res Image Gene #58: '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.clin.merged.picked.txt

  • Number of patients = 53

  • Number of significantly arm-level cnvs = 59

  • Number of selected clinical features = 4

  • 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)