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

Kidney Renal Papillary Cell Carcinoma (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/C1S75DCD

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 33 arm-level results and 8 clinical features across 104 patients, 5 significant findings detected with Q value < 0.25.

Amp Peak 6(7q22.1) cnv correlated to 'NEOPLASM.DISEASESTAGE'.
Del Peak 4(3p22.1) cnv correlated to 'LYMPH.NODE.METASTASIS'.
Del Peak 6(5p15.2) cnv correlated to 'Time to Death'.
Del Peak 24(Xq21.31) cnv correlated to 'Time to Death'.
Del Peak 25(Xq28) cnv correlated to 'Time to Death'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 33 arm-level results and 8 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 5 significant findings detected.


		Clinical Features	Time to Death	AGE	GENDER	KARNOFSKY PERFORMANCE SCORE	DISTANT METASTASIS	LYMPH NODE METASTASIS	TUMOR STAGECODE	NEOPLASM DISEASESTAGE
	nCNV (%)	nWild-Type	logrank test	t-test	Fisher's exact test	t-test	Fisher's exact test	Fisher's exact test	t-test	Fisher's exact test
Amp Peak 6(7q22 1)	0 (0%)	45	0.0667 (1.00)	0.815 (1.00)	0.092 (1.00)	0.184 (1.00)	0.505 (1.00)	0.0106 (1.00)		0.00101 (0.216)
Del Peak 4(3p22 1)	0 (0%)	97	0.273 (1.00)	0.0375 (1.00)	1 (1.00)		0.304 (1.00)	0.000216 (0.0468)		0.0455 (1.00)
Del Peak 6(5p15 2)	0 (0%)	98	0.000193 (0.0418)	0.0215 (1.00)	0.39 (1.00)		0.278 (1.00)	0.00861 (1.00)		0.0686 (1.00)
Del Peak 24(Xq21 31)	0 (0%)	88	0.000239 (0.0515)	0.182 (1.00)	0.147 (1.00)	0.398 (1.00)	0.12 (1.00)	0.0401 (1.00)		0.106 (1.00)
Del Peak 25(Xq28)	0 (0%)	89	0.000154 (0.0337)	0.248 (1.00)	0.0793 (1.00)	0.458 (1.00)	0.353 (1.00)	0.172 (1.00)		0.221 (1.00)
Amp Peak 1(2q32 1)	0 (0%)	84	0.591 (1.00)	0.397 (1.00)	0.797 (1.00)	0.501 (1.00)	0.05 (1.00)	0.0164 (1.00)		0.0676 (1.00)
Amp Peak 2(3p14 1)	0 (0%)	77	0.61 (1.00)	0.714 (1.00)	0.235 (1.00)	0.13 (1.00)	0.629 (1.00)	0.0351 (1.00)		0.23 (1.00)
Amp Peak 3(3q26 31)	0 (0%)	72	0.279 (1.00)	0.834 (1.00)	0.174 (1.00)	0.174 (1.00)	0.257 (1.00)	0.116 (1.00)		0.664 (1.00)
Amp Peak 4(5q35 2)	0 (0%)	90	0.892 (1.00)	0.967 (1.00)	1 (1.00)	0.397 (1.00)	0.651 (1.00)	0.0442 (1.00)		0.361 (1.00)
Amp Peak 5(6p12 3)	0 (0%)	100	0.565 (1.00)	0.352 (1.00)	1 (1.00)		0.213 (1.00)	0.0877 (1.00)		0.267 (1.00)
Amp Peak 7(17q25 2)	0 (0%)	34	0.525 (1.00)	0.0994 (1.00)	0.0441 (1.00)	0.561 (1.00)	0.0385 (1.00)	0.531 (1.00)		0.584 (1.00)
Amp Peak 8(19p13 2)	0 (0%)	91	0.993 (1.00)	0.0743 (1.00)	1 (1.00)	0.136 (1.00)	1 (1.00)	1 (1.00)		0.74 (1.00)
Amp Peak 9(19q13 11)	0 (0%)	100	0.375 (1.00)	0.263 (1.00)	1 (1.00)		0.716 (1.00)	0.178 (1.00)		0.807 (1.00)
Del Peak 1(1p36 31)	0 (0%)	82	0.116 (1.00)	0.66 (1.00)	0.799 (1.00)	0.377 (1.00)	0.0972 (1.00)	0.0517 (1.00)		0.0704 (1.00)
Del Peak 2(2p11 2)	0 (0%)	101	0.359 (1.00)	0.72 (1.00)	1 (1.00)		1 (1.00)	0.725 (1.00)		0.565 (1.00)
Del Peak 3(2q37 3)	0 (0%)	99	0.648 (1.00)	0.335 (1.00)	0.327 (1.00)		0.316 (1.00)	0.823 (1.00)		0.0293 (1.00)
Del Peak 5(4q33)	0 (0%)	91	0.185 (1.00)	0.393 (1.00)	0.345 (1.00)		0.102 (1.00)	0.179 (1.00)		0.114 (1.00)
Del Peak 7(5q15)	0 (0%)	96	0.606 (1.00)	0.0544 (1.00)	0.433 (1.00)		0.126 (1.00)	0.136 (1.00)		0.158 (1.00)
Del Peak 8(5q35 2)	0 (0%)	96	0.606 (1.00)	0.114 (1.00)	0.433 (1.00)		0.304 (1.00)	0.136 (1.00)		0.0455 (1.00)
Del Peak 9(6p12 3)	0 (0%)	93	0.273 (1.00)	0.724 (1.00)	0.747 (1.00)	0.248 (1.00)	0.849 (1.00)	0.181 (1.00)		0.0739 (1.00)
Del Peak 10(6q22 31)	0 (0%)	92	0.0423 (1.00)	0.903 (1.00)	0.0553 (1.00)	0.383 (1.00)	0.545 (1.00)	0.352 (1.00)		0.176 (1.00)
Del Peak 11(6q26)	0 (0%)	92	0.273 (1.00)	0.808 (1.00)	0.0553 (1.00)	0.383 (1.00)	0.741 (1.00)	0.281 (1.00)		0.141 (1.00)
Del Peak 12(9p21 3)	0 (0%)	87	0.00809 (1.00)	0.291 (1.00)	0.0214 (1.00)	0.398 (1.00)	0.0309 (1.00)	0.0046 (0.971)		0.00546 (1.00)
Del Peak 13(10p15 3)	0 (0%)	99	0.369 (1.00)	0.648 (1.00)	0.661 (1.00)		0.145 (1.00)	0.197 (1.00)		0.446 (1.00)
Del Peak 14(11q22 3)	0 (0%)	93	0.00125 (0.266)	0.0205 (1.00)	1 (1.00)		0.153 (1.00)	0.419 (1.00)		0.00963 (1.00)
Del Peak 16(14q11 2)	0 (0%)	80	0.281 (1.00)	0.989 (1.00)	0.623 (1.00)	0.445 (1.00)	0.135 (1.00)	0.138 (1.00)		0.125 (1.00)
Del Peak 17(14q23 3)	0 (0%)	81	0.26 (1.00)	0.359 (1.00)	0.461 (1.00)	0.377 (1.00)	0.0629 (1.00)	0.0284 (1.00)		0.0906 (1.00)
Del Peak 18(14q32 2)	0 (0%)	81	0.26 (1.00)	0.327 (1.00)	0.806 (1.00)	0.377 (1.00)	0.0322 (1.00)	0.0284 (1.00)		0.0989 (1.00)
Del Peak 19(15q14)	0 (0%)	90	0.00621 (1.00)	0.107 (1.00)	1 (1.00)	0.354 (1.00)	0.0311 (1.00)	0.00295 (0.626)		0.0183 (1.00)
Del Peak 20(19p13 3)	0 (0%)	96	0.124 (1.00)	0.82 (1.00)	0.714 (1.00)	0.397 (1.00)	0.482 (1.00)	0.898 (1.00)		0.255 (1.00)
Del Peak 21(19q13 2)	0 (0%)	97	0.258 (1.00)	0.478 (1.00)	1 (1.00)		1 (1.00)	0.44 (1.00)		0.0474 (1.00)
Del Peak 22(19q13 42)	0 (0%)	96	0.388 (1.00)	0.61 (1.00)	1 (1.00)		1 (1.00)	0.596 (1.00)		0.408 (1.00)
Del Peak 23(22q12 2)	0 (0%)	75	0.719 (1.00)	0.618 (1.00)	0.11 (1.00)	0.445 (1.00)	0.264 (1.00)	0.178 (1.00)		0.0165 (1.00)

'Amp Peak 6(7q22.1)' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.00101 (Fisher's exact test), Q value = 0.22

Table S1. Gene #6: 'Amp Peak 6(7q22.1)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IV
ALL	53	7	24	9
AMP PEAK 6(7Q22.1) CNV	37	2	6	5
AMP PEAK 6(7Q22.1) WILD-TYPE	16	5	18	4

Figure S1. Get High-res Image Gene #6: 'Amp Peak 6(7q22.1)' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

'Del Peak 4(3p22.1)' versus 'LYMPH.NODE.METASTASIS'

P value = 0.000216 (Fisher's exact test), Q value = 0.047

Table S2. Gene #13: 'Del Peak 4(3p22.1)' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1	N2	NX
ALL	20	12	4	68
DEL PEAK 4(3P22.1) CNV	3	4	0	0
DEL PEAK 4(3P22.1) WILD-TYPE	17	8	4	68

Figure S2. Get High-res Image Gene #13: 'Del Peak 4(3p22.1)' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

'Del Peak 6(5p15.2)' versus 'Time to Death'

P value = 0.000193 (logrank test), Q value = 0.042

Table S3. Gene #15: 'Del Peak 6(5p15.2)' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	97	14	0.0 - 182.7 (13.7)
DEL PEAK 6(5P15.2) CNV	5	2	0.0 - 22.9 (3.7)
DEL PEAK 6(5P15.2) WILD-TYPE	92	12	0.0 - 182.7 (14.4)

Figure S3. Get High-res Image Gene #15: 'Del Peak 6(5p15.2)' versus Clinical Feature #1: 'Time to Death'

'Del Peak 24(Xq21.31)' versus 'Time to Death'

P value = 0.000239 (logrank test), Q value = 0.051

Table S4. Gene #32: 'Del Peak 24(Xq21.31)' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	97	14	0.0 - 182.7 (13.7)
DEL PEAK 24(XQ21.31) CNV	15	5	0.0 - 79.8 (9.6)
DEL PEAK 24(XQ21.31) WILD-TYPE	82	9	0.0 - 182.7 (15.1)

Figure S4. Get High-res Image Gene #32: 'Del Peak 24(Xq21.31)' versus Clinical Feature #1: 'Time to Death'

'Del Peak 25(Xq28)' versus 'Time to Death'

P value = 0.000154 (logrank test), Q value = 0.034

Table S5. Gene #33: 'Del Peak 25(Xq28)' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	97	14	0.0 - 182.7 (13.7)
DEL PEAK 25(XQ28) CNV	14	4	0.0 - 22.9 (10.3)
DEL PEAK 25(XQ28) WILD-TYPE	83	10	0.0 - 182.7 (15.5)

Figure S5. Get High-res Image Gene #33: 'Del Peak 25(Xq28)' versus Clinical Feature #1: 'Time to Death'

Methods & Data

Input

Mutation data file = all_lesions.conf_99.cnv.cluster.txt
Clinical data file = KIRP-TP.clin.merged.picked.txt
Number of patients = 104
Number of significantly arm-level cnvs = 33
Number of selected clinical features = 8
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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