Prostate Adenocarcinoma: Correlation between copy number variation genes 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 copy number variation (cnv) genes and selected clinical features.

Summary

Testing the association between copy number variation of 42 peak regions and 3 clinical features across 146 patients, 2 significant findings detected with Q value < 0.25.

- Amp Peak 15(Xq25) cnvs correlated to 'AGE'.

- Del Peak 7(4q28.1) cnvs correlated to 'AGE'.

Results
Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 42 regions and 3 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 | RADIATIONS RADIATION REGIMENINDICATION
| nCNV (%) | nWild-Type | logrank test | t-test | Fisher's exact test
Amp Peak 15(Xq25) | 3 (2%) | 143 | 1 (1.00) | 7.25e-09 (9.14e-07) | 1 (1.00)
Del Peak 7(4q28 1) | 11 (8%) | 135 | 1 (1.00) | 0.000488 (0.061) | 1 (1.00)
Amp Peak 1(1q21 3) | 9 (6%) | 137 | 1 (1.00) | 0.835 (1.00) | 1 (1.00)
Amp Peak 2(3q26 2) | 23 (16%) | 123 | 1 (1.00) | 0.128 (1.00) | 1 (1.00)
Amp Peak 3(7p15 3) | 29 (20%) | 117 | 1 (1.00) | 0.454 (1.00) | 0.258 (1.00)
Amp Peak 4(8p11 22) | 15 (10%) | 131 | 1 (1.00) | 0.379 (1.00) | 1 (1.00)
Amp Peak 5(8q21 13) | 37 (25%) | 109 | 1 (1.00) | 0.0354 (1.00) | 0.33 (1.00)
Amp Peak 6(10q21 2) | 7 (5%) | 139 | 1 (1.00) | 0.215 (1.00) | 1 (1.00)
Amp Peak 7(12q24 32) | 7 (5%) | 139 | 1 (1.00) | 0.988 (1.00) | 0.221 (1.00)
Amp Peak 8(14q21 1) | 6 (4%) | 140 | 1 (1.00) | 0.0144 (1.00) | 0.192 (1.00)
Amp Peak 10(Xp22 11) | 4 (3%) | 142 | 1 (1.00) | 0.25 (1.00) | 1 (1.00)
Amp Peak 11(Xp21 1) | 4 (3%) | 142 | 1 (1.00) | 0.125 (1.00) | 1 (1.00)
Amp Peak 12(Xq21 1) | 7 (5%) | 139 | 1 (1.00) | 0.731 (1.00) | 1 (1.00)
Amp Peak 13(Xq21 1) | 5 (3%) | 141 | 1 (1.00) | 0.334 (1.00) | 1 (1.00)
Amp Peak 14(Xq21 31) | 5 (3%) | 141 | 1 (1.00) | 0.235 (1.00) | 1 (1.00)
Amp Peak 16(Xq25) | 6 (4%) | 140 | 1 (1.00) | 0.724 (1.00) | 1 (1.00)
Amp Peak 17(Xq27 1) | 9 (6%) | 137 | 1 (1.00) | 0.295 (1.00) | 1 (1.00)
Del Peak 1(1p31 3) | 19 (13%) | 127 | 1 (1.00) | 0.787 (1.00) | 1 (1.00)
Del Peak 2(1q23 1) | 5 (3%) | 141 | 1 (1.00) | 0.643 (1.00) | 1 (1.00)
Del Peak 3(1q42 13) | 14 (10%) | 132 | 1 (1.00) | 0.156 (1.00) | 1 (1.00)
Del Peak 4(2q22 1) | 19 (13%) | 127 | 1 (1.00) | 0.0945 (1.00) | 1 (1.00)
Del Peak 5(3p13) | 26 (18%) | 120 | 1 (1.00) | 0.319 (1.00) | 0.0396 (1.00)
Del Peak 6(3q29) | 9 (6%) | 137 | 1 (1.00) | 0.347 (1.00) | 1 (1.00)
Del Peak 8(5q11 2) | 23 (16%) | 123 | 1 (1.00) | 0.0689 (1.00) | 1 (1.00)
Del Peak 9(5q21 1) | 26 (18%) | 120 | 1 (1.00) | 0.0196 (1.00) | 0.586 (1.00)
Del Peak 10(5q22 3) | 16 (11%) | 130 | 1 (1.00) | 0.367 (1.00) | 1 (1.00)
Del Peak 11(6q15) | 49 (34%) | 97 | 1 (1.00) | 0.0337 (1.00) | 0.168 (1.00)
Del Peak 12(7q36 1) | 5 (3%) | 141 | 1 (1.00) | 0.0663 (1.00) | 1 (1.00)
Del Peak 13(8p21 3) | 87 (60%) | 59 | 1 (1.00) | 0.231 (1.00) | 1 (1.00)
Del Peak 14(8p11 21) | 47 (32%) | 99 | 1 (1.00) | 0.0851 (1.00) | 0.176 (1.00)
Del Peak 15(10q23 31) | 53 (36%) | 93 | 1 (1.00) | 0.975 (1.00) | 0.653 (1.00)
Del Peak 16(11q23 2) | 18 (12%) | 128 | 1 (1.00) | 0.577 (1.00) | 1 (1.00)
Del Peak 17(12p13 2) | 31 (21%) | 115 | 1 (1.00) | 0.768 (1.00) | 1 (1.00)
Del Peak 18(13q14 13) | 68 (47%) | 78 | 1 (1.00) | 0.00565 (0.7) | 0.184 (1.00)
Del Peak 19(16q22 3) | 45 (31%) | 101 | 1 (1.00) | 0.0237 (1.00) | 0.324 (1.00)
Del Peak 20(16q24 1) | 58 (40%) | 88 | 1 (1.00) | 0.123 (1.00) | 1 (1.00)
Del Peak 21(17p13 1) | 39 (27%) | 107 | 1 (1.00) | 0.447 (1.00) | 1 (1.00)
Del Peak 22(17q21 31) | 26 (18%) | 120 | 1 (1.00) | 0.675 (1.00) | 1 (1.00)
Del Peak 23(18q22 1) | 37 (25%) | 109 | 1 (1.00) | 0.659 (1.00) | 1 (1.00)
Del Peak 24(18q23) | 43 (29%) | 103 | 1 (1.00) | 0.0888 (1.00) | 0.631 (1.00)
Del Peak 25(21q22 2) | 48 (33%) | 98 | 1 (1.00) | 0.858 (1.00) | 0.331 (1.00)
Del Peak 26(21q22 3) | 46 (32%) | 100 | 1 (1.00) | 0.689 (1.00) | 0.18 (1.00)

'Amp Peak 15(Xq25) mutation analysis' versus 'AGE'

P value = 7.25e-09 (t-test), Q value = 9.1e-07

Table S1. Gene #14: 'Amp Peak 15(Xq25) mutation analysis' versus Clinical Feature #2: 'AGE'

| nPatients | Mean (Std.Dev)
--- | --- | ---
ALL | 146 | 60.4 (7.0)
AMP PEAK 15(XQ25) MUTATED | 3 | 65.7 (0.6)
AMP PEAK 15(XQ25) WILD-TYPE | 143 | 60.3 (7.0)

Figure S1. Get High-res Image Gene #14: 'Amp Peak 15(Xq25) mutation analysis' versus Clinical Feature #2: 'AGE'

'Del Peak 7(4q28.1) mutation analysis' versus 'AGE'

P value = 0.000488 (t-test), Q value = 0.061

Table S2. Gene #23: 'Del Peak 7(4q28.1) mutation analysis' versus Clinical Feature #2: 'AGE'

| nPatients | Mean (Std.Dev)
--- | --- | ---
ALL | 146 | 60.4 (7.0)
DEL PEAK 7(4Q28.1) MUTATED | 11 | 65.5 (3.7)
DEL PEAK 7(4Q28.1) WILD-TYPE | 135 | 60.0 (7.0)

Figure S2. Get High-res Image Gene #23: 'Del Peak 7(4q28.1) mutation analysis' versus Clinical Feature #2: 'AGE'

Methods & Data
Input

- Copy number data file = All Lesions File (all_lesions.conf_##.txt, where ## is the confidence level). The all lesions file is from GISTIC pipeline and summarizes the results from the GISTIC run. It contains data about the significant regions of amplification and deletion as well as which samples are amplified or deleted in each of these regions. The identified regions are listed down the first column, and the samples are listed across the first row, starting in column 10.

- Clinical data file = PRAD-TP.clin.merged.picked.txt

- Number of patients = 146

- Number of copy number variation regions = 42

- Number of selected clinical features = 3

- Exclude regions that fewer than K tumors have alterations, K = 3

Survival analysis

For survival clinical features, the Kaplan-Meier survival curves of tumors with and without gene cnvs 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 cnvs 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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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)
[5] GISTIC_version2
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