Correlation between copy number variation genes (focal events) and selected clinical features
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (Primary solid tumor)
15 January 2014  |  analyses__2014_01_15
Maintainer Information
Citation Information
doi:10.7908/C1BC3WZD
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 copy number variation genes (focal events) and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1BC3WZD
Overview
Introduction

This pipeline computes the correlation between significant copy number variation (cnv focal) genes and selected clinical features.

Summary

Testing the association between copy number variation 53 focal events and 9 clinical features across 78 patients, 3 significant findings detected with Q value < 0.25.

  • amp_19q13.13 cnv correlated to 'Time to Death'.

  • del_7q34 cnv correlated to 'Time to Death'.

  • del_14q32.31 cnv correlated to 'NUMBER.OF.LYMPH.NODES'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 53 focal events and 9 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 PATHOLOGY
T
STAGE 		PATHOLOGY
N
STAGE 		PATHOLOGY
M
STAGE 		HISTOLOGICAL
TYPE 		RADIATIONS
RADIATION
REGIMENINDICATION 		NUMBERPACKYEARSSMOKED NUMBER
OF
LYMPH
NODES
nCNV (%) nWild-Type logrank test t-test Fisher's exact test Fisher's exact test Fisher's exact test Chi-square test Fisher's exact test t-test t-test
amp 19q13 13 23 (29%) 55 0.000486
(0.226) 		0.982
(1.00) 		0.405
(1.00) 		0.263
(1.00) 		0.705
(1.00) 		0.516
(1.00) 		0.00141
(0.65) 		0.935
(1.00) 		0.0954
(1.00)
del 7q34 14 (18%) 64 0.000262
(0.122) 		0.421
(1.00) 		0.312
(1.00) 		0.286
(1.00) 		0.122
(1.00) 		0.882
(1.00) 		0.0499
(1.00) 		0.722
(1.00) 		0.109
(1.00)
del 14q32 31 10 (13%) 68 0.167
(1.00) 		0.138
(1.00) 		0.273
(1.00) 		0.262
(1.00) 		0.485
(1.00) 		0.0762
(1.00) 		1
(1.00) 		0.000254
(0.118)
amp 1q21 3 42 (54%) 36 0.0407
(1.00) 		0.451
(1.00) 		0.206
(1.00) 		0.795
(1.00) 		0.176
(1.00) 		0.279
(1.00) 		0.361
(1.00) 		0.96
(1.00) 		0.332
(1.00)
amp 2p24 3 18 (23%) 60 0.876
(1.00) 		0.0464
(1.00) 		0.362
(1.00) 		1
(1.00) 		1
(1.00) 		0.331
(1.00) 		1
(1.00) 		0.809
(1.00) 		0.689
(1.00)
amp 3q26 2 59 (76%) 19 0.84
(1.00) 		0.994
(1.00) 		0.269
(1.00) 		0.554
(1.00) 		0.58
(1.00) 		0.00162
(0.745) 		0.169
(1.00) 		0.746
(1.00) 		0.0334
(1.00)
amp 3q28 58 (74%) 20 0.659
(1.00) 		0.866
(1.00) 		0.26
(1.00) 		0.776
(1.00) 		0.676
(1.00) 		0.003
(1.00) 		0.496
(1.00) 		0.746
(1.00) 		0.391
(1.00)
amp 4q12 8 (10%) 70 0.534
(1.00) 		0.792
(1.00) 		0.376
(1.00) 		1
(1.00) 		0.716
(1.00) 		0.0402
(1.00) 		0.614
(1.00) 		0.946
(1.00) 		0.284
(1.00)
amp 5p15 33 28 (36%) 50 0.565
(1.00) 		0.509
(1.00) 		1
(1.00) 		0.785
(1.00) 		0.82
(1.00) 		0.0937
(1.00) 		0.761
(1.00) 		0.306
(1.00) 		0.426
(1.00)
amp 6p21 33 21 (27%) 57 0.831
(1.00) 		0.53
(1.00) 		1
(1.00) 		0.77
(1.00) 		0.509
(1.00) 		0.31
(1.00) 		0.74
(1.00) 		0.787
(1.00) 		0.176
(1.00)
amp 7p11 2 15 (19%) 63 0.0225
(1.00) 		0.699
(1.00) 		0.18
(1.00) 		0.163
(1.00) 		1
(1.00) 		0.852
(1.00) 		0.115
(1.00) 		0.0975
(1.00)
amp 8q24 21 33 (42%) 45 0.588
(1.00) 		0.191
(1.00) 		0.21
(1.00) 		1
(1.00) 		0.493
(1.00) 		0.446
(1.00) 		0.54
(1.00) 		0.183
(1.00) 		0.99
(1.00)
amp 9p24 1 12 (15%) 66 0.0937
(1.00) 		0.644
(1.00) 		0.18
(1.00) 		0.163
(1.00) 		0.825
(1.00) 		0.93
(1.00) 		0.678
(1.00) 		0.242
(1.00) 		0.605
(1.00)
amp 11p13 6 (8%) 72 0.0073
(1.00) 		0.677
(1.00) 		0.238
(1.00) 		1
(1.00) 		0.661
(1.00) 		0.964
(1.00) 		1
(1.00)
amp 11q13 3 10 (13%) 68 0.675
(1.00) 		0.267
(1.00) 		1
(1.00) 		1
(1.00) 		0.567
(1.00) 		0.122
(1.00) 		0.357
(1.00) 		0.299
(1.00) 		0.666
(1.00)
amp 11q22 1 13 (17%) 65 0.33
(1.00) 		0.000691
(0.32) 		0.74
(1.00) 		0.743
(1.00) 		1
(1.00) 		0.908
(1.00) 		0.214
(1.00) 		0.445
(1.00)
amp 13q22 1 13 (17%) 65 0.0577
(1.00) 		0.912
(1.00) 		1
(1.00) 		0.286
(1.00) 		1
(1.00) 		0.878
(1.00) 		0.683
(1.00) 		0.00221
(1.00) 		0.113
(1.00)
amp 15q26 1 16 (21%) 62 0.61
(1.00) 		0.724
(1.00) 		0.122
(1.00) 		0.745
(1.00) 		0.708
(1.00) 		0.141
(1.00) 		0.723
(1.00) 		0.744
(1.00)
amp 16p13 13 14 (18%) 64 0.839
(1.00) 		0.052
(1.00) 		0.00276
(1.00) 		0.0494
(1.00) 		0.205
(1.00) 		0.554
(1.00) 		0.693
(1.00) 		0.012
(1.00) 		0.235
(1.00)
amp 17q12 9 (12%) 69 1
(1.00) 		0.39
(1.00) 		0.0255
(1.00) 		0.116
(1.00) 		0.594
(1.00) 		0.968
(1.00) 		0.64
(1.00) 		0.565
(1.00)
amp 17q25 1 20 (26%) 58 0.809
(1.00) 		0.47
(1.00) 		0.15
(1.00) 		0.078
(1.00) 		1
(1.00) 		0.654
(1.00) 		1
(1.00) 		0.735
(1.00) 		0.311
(1.00)
amp 19q13 32 22 (28%) 56 0.0257
(1.00) 		0.804
(1.00) 		0.782
(1.00) 		0.576
(1.00) 		0.888
(1.00) 		0.563
(1.00) 		0.000915
(0.423) 		0.801
(1.00) 		0.4
(1.00)
amp 20q11 21 31 (40%) 47 0.354
(1.00) 		0.581
(1.00) 		0.435
(1.00) 		0.187
(1.00) 		0.413
(1.00) 		0.553
(1.00) 		1
(1.00) 		0.855
(1.00) 		0.62
(1.00)
amp xq28 14 (18%) 64 0.186
(1.00) 		0.0773
(1.00) 		0.352
(1.00) 		0.202
(1.00) 		1
(1.00) 		0.17
(1.00) 		1
(1.00) 		0.237
(1.00) 		0.0479
(1.00)
del 1p36 23 12 (15%) 66 0.93
(1.00) 		0.829
(1.00) 		1
(1.00) 		1
(1.00) 		0.341
(1.00) 		0.149
(1.00) 		0.411
(1.00) 		0.322
(1.00) 		0.703
(1.00)
del 2q22 1 12 (15%) 66 0.96
(1.00) 		0.109
(1.00) 		0.312
(1.00) 		0.723
(1.00) 		0.809
(1.00) 		0.442
(1.00) 		0.0242
(1.00) 		0.244
(1.00) 		0.544
(1.00)
del 2q37 1 31 (40%) 47 0.467
(1.00) 		0.00839
(1.00) 		0.195
(1.00) 		0.794
(1.00) 		0.661
(1.00) 		0.675
(1.00) 		0.758
(1.00) 		0.316
(1.00) 		0.15
(1.00)
del 3p14 2 31 (40%) 47 0.0786
(1.00) 		0.524
(1.00) 		0.444
(1.00) 		0.0319
(1.00) 		0.661
(1.00) 		0.0528
(1.00) 		0.12
(1.00) 		0.639
(1.00) 		0.0333
(1.00)
del 4q22 1 15 (19%) 63 0.00737
(1.00) 		0.374
(1.00) 		0.756
(1.00) 		0.102
(1.00) 		0.708
(1.00) 		0.497
(1.00) 		0.115
(1.00) 		0.784
(1.00) 		0.131
(1.00)
del 4q35 2 21 (27%) 57 0.0301
(1.00) 		0.503
(1.00) 		0.775
(1.00) 		0.559
(1.00) 		0.668
(1.00) 		0.128
(1.00) 		0.32
(1.00) 		0.328
(1.00) 		0.179
(1.00)
del 5q15 21 (27%) 57 0.0437
(1.00) 		0.128
(1.00) 		0.39
(1.00) 		0.143
(1.00) 		0.758
(1.00) 		0.265
(1.00) 		0.32
(1.00) 		0.842
(1.00) 		0.188
(1.00)
del 5q35 2 22 (28%) 56 0.0521
(1.00) 		0.196
(1.00) 		0.775
(1.00) 		0.242
(1.00) 		1
(1.00) 		0.304
(1.00) 		0.5
(1.00) 		0.842
(1.00) 		0.144
(1.00)
del 6p24 2 9 (12%) 69 0.654
(1.00) 		0.024
(1.00) 		1
(1.00) 		0.0471
(1.00) 		0.764
(1.00) 		0.968
(1.00) 		1
(1.00) 		0.389
(1.00)
del 6q26 23 (29%) 55 0.106
(1.00) 		0.457
(1.00) 		1
(1.00) 		0.559
(1.00) 		0.546
(1.00) 		0.508
(1.00) 		0.324
(1.00) 		0.101
(1.00) 		0.824
(1.00)
del 10q23 31 18 (23%) 60 0.0468
(1.00) 		0.602
(1.00) 		0.762
(1.00) 		0.0642
(1.00) 		0.734
(1.00) 		0.867
(1.00) 		0.164
(1.00) 		0.442
(1.00) 		0.0648
(1.00)
del 11p15 1 27 (35%) 51 0.302
(1.00) 		0.842
(1.00) 		1
(1.00) 		0.412
(1.00) 		0.579
(1.00) 		0.341
(1.00) 		1
(1.00) 		0.516
(1.00) 		0.179
(1.00)
del 11q23 3 44 (56%) 34 0.778
(1.00) 		0.595
(1.00) 		0.314
(1.00) 		1
(1.00) 		1
(1.00) 		0.0679
(1.00) 		0.37
(1.00) 		0.419
(1.00) 		0.617
(1.00)
del 11q25 49 (63%) 29 0.229
(1.00) 		0.418
(1.00) 		0.438
(1.00) 		0.603
(1.00) 		1
(1.00) 		0.0181
(1.00) 		0.351
(1.00) 		0.883
(1.00) 		0.675
(1.00)
del 13q12 12 24 (31%) 54 0.317
(1.00) 		0.593
(1.00) 		1
(1.00) 		0.398
(1.00) 		0.355
(1.00) 		0.178
(1.00) 		1
(1.00) 		0.628
(1.00) 		0.152
(1.00)
del 13q14 2 26 (33%) 52 0.0831
(1.00) 		0.267
(1.00) 		1
(1.00) 		0.412
(1.00) 		0.578
(1.00) 		0.131
(1.00) 		1
(1.00) 		0.652
(1.00) 		0.263
(1.00)
del 15q15 1 17 (22%) 61 0.516
(1.00) 		0.562
(1.00) 		1
(1.00) 		0.358
(1.00) 		0.861
(1.00) 		0.285
(1.00) 		0.277
(1.00) 		0.387
(1.00) 		0.976
(1.00)
del 16q12 1 16 (21%) 62 0.82
(1.00) 		0.00863
(1.00) 		0.525
(1.00) 		0.0501
(1.00) 		1
(1.00) 		0.036
(1.00) 		0.0591
(1.00) 		0.302
(1.00)
del 16q23 1 14 (18%) 64 0.571
(1.00) 		0.0488
(1.00) 		0.743
(1.00) 		0.741
(1.00) 		1
(1.00) 		0.00223
(1.00) 		0.443
(1.00) 		0.409
(1.00) 		0.937
(1.00)
del 17p12 22 (28%) 56 0.302
(1.00) 		0.965
(1.00) 		0.39
(1.00) 		1
(1.00) 		0.381
(1.00) 		0.781
(1.00) 		1
(1.00) 		0.845
(1.00) 		0.793
(1.00)
del 17q25 3 14 (18%) 64 0.0333
(1.00) 		0.686
(1.00) 		0.74
(1.00) 		0.489
(1.00) 		0.825
(1.00) 		0.541
(1.00) 		1
(1.00) 		0.752
(1.00) 		0.67
(1.00)
del 18q21 2 19 (24%) 59 0.866
(1.00) 		0.39
(1.00) 		0.554
(1.00) 		0.24
(1.00) 		0.419
(1.00) 		0.1
(1.00) 		0.724
(1.00) 		0.282
(1.00) 		0.337
(1.00)
del 19p13 3 18 (23%) 60 0.449
(1.00) 		0.528
(1.00) 		0.121
(1.00) 		1
(1.00) 		1
(1.00) 		0.373
(1.00) 		0.164
(1.00) 		0.504
(1.00) 		0.415
(1.00)
del 19q13 33 9 (12%) 69 0.0916
(1.00) 		0.342
(1.00) 		0.257
(1.00) 		1
(1.00) 		0.218
(1.00) 		0.968
(1.00) 		1
(1.00) 		0.412
(1.00)
del 20p12 1 13 (17%) 65 0.185
(1.00) 		0.522
(1.00) 		0.74
(1.00) 		1
(1.00) 		0.825
(1.00) 		0.492
(1.00) 		0.11
(1.00) 		0.677
(1.00) 		0.805
(1.00)
del 21q21 1 14 (18%) 64 0.031
(1.00) 		0.29
(1.00) 		0.756
(1.00) 		0.745
(1.00) 		1
(1.00) 		0.882
(1.00) 		1
(1.00) 		0.234
(1.00)
del 22q13 32 18 (23%) 60 0.405
(1.00) 		0.34
(1.00) 		0.761
(1.00) 		0.356
(1.00) 		0.734
(1.00) 		0.292
(1.00) 		0.483
(1.00) 		0.0522
(1.00) 		0.135
(1.00)
del xp11 3 22 (28%) 56 0.275
(1.00) 		0.721
(1.00) 		0.775
(1.00) 		1
(1.00) 		0.776
(1.00) 		0.304
(1.00) 		0.174
(1.00) 		0.0488
(1.00) 		0.529
(1.00)
del xq21 33 15 (19%) 63 0.00347
(1.00) 		0.686
(1.00) 		0.529
(1.00) 		0.511
(1.00) 		0.825
(1.00) 		0.852
(1.00) 		0.262
(1.00) 		0.411
(1.00) 		0.393
(1.00)
'amp_19q13.13' versus 'Time to Death'

P value = 0.000486 (logrank test), Q value = 0.23

Table S1.  Gene #19: 'amp_19q13.13' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 76 11 0.0 - 177.0 (6.0)
AMP PEAK 19(19Q13.13) MUTATED 23 7 0.1 - 78.3 (6.0)
AMP PEAK 19(19Q13.13) WILD-TYPE 53 4 0.0 - 177.0 (6.1)

Figure S1.  Get High-res Image Gene #19: 'amp_19q13.13' versus Clinical Feature #1: 'Time to Death'

'del_7q34' versus 'Time to Death'

P value = 0.000262 (logrank test), Q value = 0.12

Table S2.  Gene #33: 'del_7q34' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 76 11 0.0 - 177.0 (6.0)
DEL PEAK 11(7Q34) MUTATED 14 6 0.6 - 67.5 (12.7)
DEL PEAK 11(7Q34) WILD-TYPE 62 5 0.0 - 177.0 (5.9)

Figure S2.  Get High-res Image Gene #33: 'del_7q34' versus Clinical Feature #1: 'Time to Death'

'del_14q32.31' versus 'NUMBER.OF.LYMPH.NODES'

P value = 0.000254 (t-test), Q value = 0.12

Table S3.  Gene #40: 'del_14q32.31' versus Clinical Feature #9: 'NUMBER.OF.LYMPH.NODES'

nPatients Mean (Std.Dev)
ALL 64 0.6 (1.3)
DEL PEAK 18(14Q32.31) MUTATED 9 0.0 (0.0)
DEL PEAK 18(14Q32.31) WILD-TYPE 55 0.7 (1.3)

Figure S3.  Get High-res Image Gene #40: 'del_14q32.31' versus Clinical Feature #9: 'NUMBER.OF.LYMPH.NODES'

Methods & Data
Input

  • Copy number data file = transformed.cor.cli.txt

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

  • Number of patients = 78

  • Number of significantly focal cnvs = 53

  • Number of selected clinical features = 9

  • 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

Chi-square test

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

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] 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] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)
[5] 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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