Correlation between copy number variation genes (focal) and selected clinical features

Prostate Adenocarcinoma (Primary solid tumor)

23 May 2013 | analyses__2013_05_23

Maintainer Information

Citation Information

Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)

Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between copy number variation genes (focal) and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C18W3BCQ

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 47 arm-level results and 6 clinical features across 155 patients, 2 significant findings detected with Q value < 0.25.

Amp Peak 19(Xq25) cnv correlated to 'AGE'.
Del Peak 8(4q28.2) cnv correlated to 'AGE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 47 arm-level results and 6 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	LYMPH NODE METASTASIS	COMPLETENESS OF RESECTION	NUMBER OF LYMPH NODES	TUMOR STAGECODE
	nCNV (%)	nWild-Type	logrank test	t-test	Fisher's exact test	Fisher's exact test	t-test	t-test
Amp Peak 19(Xq25)	0 (0%)	152	1 (1.00)	8.18e-09 (1.92e-06)	1 (1.00)	1 (1.00)	0.00151 (0.348)
Del Peak 8(4q28 2)	0 (0%)	141	1 (1.00)	5.4e-05 (0.0126)	1 (1.00)	1 (1.00)	0.142 (1.00)
Amp Peak 1(1q21 3)	0 (0%)	145	1 (1.00)	0.617 (1.00)	0.304 (1.00)	0.728 (1.00)	0.518 (1.00)
Amp Peak 2(3q26 2)	0 (0%)	131	1 (1.00)	0.107 (1.00)	0.283 (1.00)	1 (1.00)	0.272 (1.00)
Amp Peak 3(7p15 3)	0 (0%)	124	1 (1.00)	0.399 (1.00)	0.511 (1.00)	0.0474 (1.00)	0.341 (1.00)
Amp Peak 4(7q34)	0 (0%)	127	1 (1.00)	0.125 (1.00)	1 (1.00)	0.342 (1.00)	0.605 (1.00)
Amp Peak 5(8p11 22)	0 (0%)	140	1 (1.00)	0.375 (1.00)	0.0382 (1.00)	0.44 (1.00)	0.266 (1.00)
Amp Peak 6(8q21 13)	0 (0%)	115	1 (1.00)	0.0411 (1.00)	0.359 (1.00)	0.83 (1.00)	0.571 (1.00)
Amp Peak 7(11q13 2)	0 (0%)	147	1 (1.00)	0.622 (1.00)	0.0437 (1.00)	0.154 (1.00)	0.288 (1.00)
Amp Peak 8(12q24 32)	0 (0%)	148	1 (1.00)	0.984 (1.00)	0.172 (1.00)	0.229 (1.00)	0.407 (1.00)
Amp Peak 9(14q21 1)	0 (0%)	147	1 (1.00)	0.00156 (0.355)	0.567 (1.00)	0.291 (1.00)	0.683 (1.00)
Amp Peak 10(20q13 33)	0 (0%)	143	1 (1.00)	0.00502 (1.00)	0.36 (1.00)	0.0382 (1.00)	0.00149 (0.348)
Amp Peak 11(21q21 3)	0 (0%)	150	1 (1.00)	0.0233 (1.00)	0.448 (1.00)	0.611 (1.00)	0.534 (1.00)
Amp Peak 12(Xp22 11)	0 (0%)	150	1 (1.00)	0.704 (1.00)	0.448 (1.00)	1 (1.00)	0.644 (1.00)
Amp Peak 13(Xp22 11)	0 (0%)	150	1 (1.00)	0.129 (1.00)	0.448 (1.00)	0.604 (1.00)	0.644 (1.00)
Amp Peak 14(Xp21 1)	0 (0%)	151	1 (1.00)	0.124 (1.00)	0.377 (1.00)	1 (1.00)	0.87 (1.00)
Amp Peak 15(Xq12)	0 (0%)	152	1 (1.00)	0.642 (1.00)	1 (1.00)	0.519 (1.00)	0.00151 (0.348)
Amp Peak 16(Xq21 1)	0 (0%)	148	1 (1.00)	0.725 (1.00)	0.567 (1.00)	0.405 (1.00)	0.783 (1.00)
Amp Peak 17(Xq21 1)	0 (0%)	150	1 (1.00)	0.331 (1.00)	0.0937 (1.00)	0.611 (1.00)	0.351 (1.00)
Amp Peak 18(Xq21 31)	0 (0%)	150	1 (1.00)	0.234 (1.00)	1 (1.00)	0.611 (1.00)	0.00151 (0.348)
Amp Peak 20(Xq25)	0 (0%)	149	1 (1.00)	0.728 (1.00)	0.511 (1.00)	0.399 (1.00)	0.826 (1.00)
Amp Peak 21(Xq27 1)	0 (0%)	146	1 (1.00)	0.294 (1.00)	0.598 (1.00)	1 (1.00)	0.0015 (0.348)
Del Peak 1(1p31 3)	0 (0%)	136	1 (1.00)	0.78 (1.00)	0.69 (1.00)	0.652 (1.00)	0.81 (1.00)
Del Peak 2(1p21 3)	0 (0%)	143	1 (1.00)	0.837 (1.00)	0.348 (1.00)	0.501 (1.00)	0.282 (1.00)
Del Peak 3(1q23 1)	0 (0%)	148	1 (1.00)	0.609 (1.00)	1 (1.00)	1 (1.00)	0.00151 (0.348)
Del Peak 4(1q42 13)	0 (0%)	141	1 (1.00)	0.154 (1.00)	0.654 (1.00)	1 (1.00)	0.705 (1.00)
Del Peak 5(2q22 1)	0 (0%)	136	1 (1.00)	0.0933 (1.00)	1 (1.00)	0.817 (1.00)	0.564 (1.00)
Del Peak 6(3p13)	0 (0%)	129	1 (1.00)	0.326 (1.00)	1 (1.00)	0.728 (1.00)	0.751 (1.00)
Del Peak 7(3q29)	0 (0%)	145	1 (1.00)	0.243 (1.00)	1 (1.00)	1 (1.00)	0.977 (1.00)
Del Peak 9(5q11 2)	0 (0%)	132	1 (1.00)	0.234 (1.00)	0.00227 (0.514)	1 (1.00)	0.0738 (1.00)
Del Peak 10(5q21 1)	0 (0%)	129	1 (1.00)	0.0187 (1.00)	0.164 (1.00)	0.485 (1.00)	0.29 (1.00)
Del Peak 11(6q15)	0 (0%)	105	1 (1.00)	0.0507 (1.00)	0.0494 (1.00)	0.587 (1.00)	0.0275 (1.00)
Del Peak 12(7q36 1)	0 (0%)	148	1 (1.00)	0.329 (1.00)	0.131 (1.00)	1 (1.00)	0.414 (1.00)
Del Peak 13(8p21 3)	0 (0%)	62	1 (1.00)	0.296 (1.00)	0.0473 (1.00)	0.864 (1.00)	0.0104 (1.00)
Del Peak 14(8p11 21)	0 (0%)	103	1 (1.00)	0.174 (1.00)	0.776 (1.00)	0.0433 (1.00)	0.607 (1.00)
Del Peak 15(9p22 3)	0 (0%)	141	1 (1.00)	0.24 (1.00)	0.00914 (1.00)	0.774 (1.00)	0.0994 (1.00)
Del Peak 16(10q23 31)	0 (0%)	97	1 (1.00)	0.997 (1.00)	0.0469 (1.00)	0.889 (1.00)	0.348 (1.00)
Del Peak 17(11q23 2)	0 (0%)	136	1 (1.00)	0.69 (1.00)	0.692 (1.00)	0.805 (1.00)	0.0614 (1.00)
Del Peak 18(12p13 2)	0 (0%)	123	1 (1.00)	0.767 (1.00)	0.119 (1.00)	0.719 (1.00)	0.49 (1.00)
Del Peak 19(13q14 13)	0 (0%)	84	1 (1.00)	0.0126 (1.00)	0.285 (1.00)	0.497 (1.00)	0.263 (1.00)
Del Peak 20(16q24 1)	0 (0%)	91	1 (1.00)	0.201 (1.00)	0.27 (1.00)	0.51 (1.00)	0.153 (1.00)
Del Peak 21(17p13 1)	0 (0%)	115	1 (1.00)	0.48 (1.00)	0.119 (1.00)	0.863 (1.00)	0.276 (1.00)
Del Peak 22(17q21 31)	0 (0%)	126	1 (1.00)	0.645 (1.00)	0.738 (1.00)	0.317 (1.00)	0.367 (1.00)
Del Peak 23(18q22 1)	0 (0%)	115	1 (1.00)	0.834 (1.00)	0.527 (1.00)	0.773 (1.00)	0.585 (1.00)
Del Peak 24(18q23)	0 (0%)	109	1 (1.00)	0.144 (1.00)	0.0394 (1.00)	0.495 (1.00)	0.167 (1.00)
Del Peak 25(21q22 2)	0 (0%)	103	1 (1.00)	0.838 (1.00)	0.042 (1.00)	0.504 (1.00)	0.145 (1.00)
Del Peak 26(21q22 3)	0 (0%)	105	1 (1.00)	0.672 (1.00)	0.0208 (1.00)	0.543 (1.00)	0.112 (1.00)

'Amp Peak 19(Xq25)' versus 'AGE'

P value = 8.18e-09 (t-test), Q value = 1.9e-06

Table S1. Gene #19: 'Amp Peak 19(Xq25)' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	154	60.4 (6.9)
AMP PEAK 19(XQ25) CNV	3	65.7 (0.6)
AMP PEAK 19(XQ25) WILD-TYPE	151	60.3 (6.9)

Figure S1. Get High-res Image Gene #19: 'Amp Peak 19(Xq25)' versus Clinical Feature #2: 'AGE'

'Del Peak 8(4q28.2)' versus 'AGE'

P value = 5.4e-05 (t-test), Q value = 0.013

Table S2. Gene #29: 'Del Peak 8(4q28.2)' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	154	60.4 (6.9)
DEL PEAK 8(4Q28.2) CNV	14	65.2 (3.5)
DEL PEAK 8(4Q28.2) WILD-TYPE	140	59.9 (6.9)

Figure S2. Get High-res Image Gene #29: 'Del Peak 8(4q28.2)' versus Clinical Feature #2: 'AGE'

Methods & Data

Input

Mutation data file = all_lesions.conf_99.cnv.cluster.txt
Clinical data file = PRAD-TP.clin.merged.picked.txt
Number of patients = 155
Number of significantly arm-level cnvs = 47
Number of selected clinical features = 6
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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