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

Liver Hepatocellular Carcinoma (Primary solid tumor)

16 April 2014 | analyses__2014_04_16

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 (2014): Correlation between copy number variation genes (focal events) and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1K64GQ4

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 56 focal events and 8 clinical features across 149 patients, one significant finding detected with Q value < 0.25.

del_13q14.2 cnv correlated to 'PATHOLOGY.T.STAGE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 56 focal events and 8 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	NEOPLASM DISEASESTAGE	PATHOLOGY T STAGE	PATHOLOGY N STAGE	PATHOLOGY M STAGE	GENDER	COMPLETENESS OF RESECTION
	nCNV (%)	nWild-Type	logrank test	t-test	Chi-square test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test
del 13q14 2	68 (46%)	81	0.185 (1.00)	0.781 (1.00)	0.0591 (1.00)	0.000294 (0.132)	1 (1.00)	0.563 (1.00)	0.243 (1.00)	0.329 (1.00)
amp 1p22 3	34 (23%)	115	0.584 (1.00)	0.235 (1.00)	0.338 (1.00)	0.675 (1.00)	0.492 (1.00)	0.128 (1.00)	1 (1.00)	0.0582 (1.00)
amp 1q22	110 (74%)	39	0.0345 (1.00)	0.394 (1.00)	0.367 (1.00)	0.173 (1.00)	1 (1.00)	0.64 (1.00)	0.567 (1.00)	0.6 (1.00)
amp 1q42 3	104 (70%)	45	0.135 (1.00)	0.805 (1.00)	0.0811 (1.00)	0.0199 (1.00)	0.552 (1.00)	0.666 (1.00)	0.368 (1.00)	0.75 (1.00)
amp 2p24 1	35 (23%)	114	0.545 (1.00)	0.22 (1.00)	0.749 (1.00)	0.388 (1.00)	0.121 (1.00)	0.488 (1.00)	0.0468 (1.00)	0.628 (1.00)
amp 2q31 2	31 (21%)	118	0.131 (1.00)	0.659 (1.00)	0.576 (1.00)	0.557 (1.00)	0.452 (1.00)	0.659 (1.00)	0.0218 (1.00)	0.546 (1.00)
amp 3q26 31	31 (21%)	118	0.483 (1.00)	0.335 (1.00)	0.389 (1.00)	0.291 (1.00)	0.389 (1.00)	0.659 (1.00)	0.836 (1.00)	1 (1.00)
amp 4q13 3	15 (10%)	134	0.904 (1.00)	0.536 (1.00)	0.602 (1.00)	0.821 (1.00)	1 (1.00)	0.502 (1.00)	0.269 (1.00)	0.00994 (1.00)
amp 5p15 33	71 (48%)	78	0.901 (1.00)	0.917 (1.00)	0.0259 (1.00)	0.00574 (1.00)	1 (1.00)	0.322 (1.00)	0.868 (1.00)	1 (1.00)
amp 5q35 3	54 (36%)	95	0.72 (1.00)	0.14 (1.00)	0.464 (1.00)	0.597 (1.00)	0.549 (1.00)	1 (1.00)	0.6 (1.00)	0.0705 (1.00)
amp 6p25 2	62 (42%)	87	0.0946 (1.00)	0.701 (1.00)	0.354 (1.00)	0.242 (1.00)	1 (1.00)	0.75 (1.00)	0.61 (1.00)	0.673 (1.00)
amp 6p21 1	62 (42%)	87	0.581 (1.00)	0.315 (1.00)	0.326 (1.00)	0.993 (1.00)	0.286 (1.00)	0.653 (1.00)	0.395 (1.00)	0.673 (1.00)
amp 6q12	44 (30%)	105	0.832 (1.00)	0.814 (1.00)	0.121 (1.00)	0.96 (1.00)	0.201 (1.00)	0.119 (1.00)	0.358 (1.00)	0.453 (1.00)
amp 6q12	31 (21%)	118	0.771 (1.00)	0.34 (1.00)	0.559 (1.00)	0.978 (1.00)	1 (1.00)	0.185 (1.00)	0.535 (1.00)	0.301 (1.00)
amp 7q21 2	56 (38%)	93	0.986 (1.00)	0.104 (1.00)	0.13 (1.00)	0.227 (1.00)	0.28 (1.00)	0.525 (1.00)	0.604 (1.00)	0.566 (1.00)
amp 7q31 2	53 (36%)	96	0.581 (1.00)	0.238 (1.00)	0.14 (1.00)	0.3 (1.00)	0.226 (1.00)	0.683 (1.00)	0.726 (1.00)	0.656 (1.00)
amp 8q11 1	58 (39%)	91	0.388 (1.00)	0.663 (1.00)	0.239 (1.00)	0.169 (1.00)	0.55 (1.00)	0.526 (1.00)	0.00347 (1.00)	0.924 (1.00)
amp 8q24 21	88 (59%)	61	0.533 (1.00)	0.651 (1.00)	0.352 (1.00)	0.961 (1.00)	0.571 (1.00)	0.746 (1.00)	0.0168 (1.00)	0.929 (1.00)
amp 9q34 2	20 (13%)	129	0.47 (1.00)	0.19 (1.00)	0.112 (1.00)	0.347 (1.00)	0.344 (1.00)	0.85 (1.00)	1 (1.00)	0.16 (1.00)
amp 10p15 1	30 (20%)	119	0.462 (1.00)	0.401 (1.00)	0.017 (1.00)	0.0108 (1.00)	1 (1.00)	0.0748 (1.00)	0.676 (1.00)	1 (1.00)
amp 11q13 3	28 (19%)	121	0.367 (1.00)	0.382 (1.00)	0.081 (1.00)	0.0311 (1.00)	1 (1.00)	0.202 (1.00)	1 (1.00)	0.114 (1.00)
amp 13q32 3	23 (15%)	126	0.0232 (1.00)	0.599 (1.00)	0.983 (1.00)	0.951 (1.00)	0.344 (1.00)	0.87 (1.00)	0.36 (1.00)	0.157 (1.00)
amp 15q26 3	26 (17%)	123	0.954 (1.00)	0.316 (1.00)	0.863 (1.00)	0.338 (1.00)	1 (1.00)	1 (1.00)	0.825 (1.00)	1 (1.00)
amp 16q12 1	13 (9%)	136	0.659 (1.00)	0.375 (1.00)	0.445 (1.00)	0.0918 (1.00)	0.273 (1.00)	0.8 (1.00)	0.372 (1.00)	0.416 (1.00)
amp 17p11 2	26 (17%)	123	0.723 (1.00)	0.651 (1.00)	0.237 (1.00)	0.131 (1.00)	1 (1.00)	0.205 (1.00)	0.385 (1.00)	0.0228 (1.00)
amp 17q25 3	70 (47%)	79	0.291 (1.00)	0.891 (1.00)	0.662 (1.00)	0.588 (1.00)	1 (1.00)	0.819 (1.00)	0.0931 (1.00)	0.0705 (1.00)
amp 19q13 11	41 (28%)	108	0.999 (1.00)	0.369 (1.00)	0.237 (1.00)	0.562 (1.00)	1 (1.00)	0.296 (1.00)	0.458 (1.00)	0.238 (1.00)
amp 20q13 33	50 (34%)	99	0.954 (1.00)	0.166 (1.00)	0.315 (1.00)	0.788 (1.00)	0.28 (1.00)	0.39 (1.00)	0.218 (1.00)	0.554 (1.00)
amp xq28	38 (26%)	111	0.669 (1.00)	0.0403 (1.00)	0.825 (1.00)	0.757 (1.00)	1 (1.00)	0.704 (1.00)	0.0117 (1.00)	0.943 (1.00)
del 1p36 23	71 (48%)	78	0.273 (1.00)	0.523 (1.00)	0.853 (1.00)	0.438 (1.00)	0.587 (1.00)	0.61 (1.00)	0.502 (1.00)	0.602 (1.00)
del 2q22 1	15 (10%)	134	0.00709 (1.00)	0.788 (1.00)	0.695 (1.00)	0.258 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.748 (1.00)
del 2q37 3	28 (19%)	121	0.868 (1.00)	0.556 (1.00)	0.335 (1.00)	0.0298 (1.00)	0.411 (1.00)	0.27 (1.00)	0.395 (1.00)	0.854 (1.00)
del 3p13	26 (17%)	123	0.186 (1.00)	0.979 (1.00)	0.389 (1.00)	0.063 (1.00)	0.432 (1.00)	0.602 (1.00)	0.0451 (1.00)	1 (1.00)
del 4p16 3	26 (17%)	123	0.457 (1.00)	0.462 (1.00)	0.134 (1.00)	0.985 (1.00)	0.0506 (1.00)	0.525 (1.00)	0.191 (1.00)	0.301 (1.00)
del 4q24	64 (43%)	85	0.176 (1.00)	0.114 (1.00)	0.0552 (1.00)	0.324 (1.00)	1 (1.00)	0.267 (1.00)	0.611 (1.00)	0.374 (1.00)
del 4q34 3	59 (40%)	90	0.023 (1.00)	0.177 (1.00)	0.507 (1.00)	0.63 (1.00)	0.553 (1.00)	0.421 (1.00)	0.391 (1.00)	0.753 (1.00)
del 6q16 3	56 (38%)	93	0.823 (1.00)	0.279 (1.00)	0.45 (1.00)	0.655 (1.00)	0.559 (1.00)	0.0897 (1.00)	0.3 (1.00)	0.589 (1.00)
del 6q27	58 (39%)	91	0.775 (1.00)	0.216 (1.00)	0.502 (1.00)	0.753 (1.00)	0.559 (1.00)	0.0169 (1.00)	1 (1.00)	0.632 (1.00)
del 8p23 2	97 (65%)	52	0.167 (1.00)	0.0213 (1.00)	0.35 (1.00)	1 (1.00)	0.279 (1.00)	0.37 (1.00)	0.219 (1.00)	0.959 (1.00)
del 9p21 3	57 (38%)	92	0.0678 (1.00)	0.838 (1.00)	0.123 (1.00)	0.11 (1.00)	0.294 (1.00)	0.352 (1.00)	0.303 (1.00)	0.141 (1.00)
del 9q34 2	51 (34%)	98	0.351 (1.00)	0.844 (1.00)	0.149 (1.00)	0.34 (1.00)	0.239 (1.00)	0.0815 (1.00)	0.725 (1.00)	0.554 (1.00)
del 10q23 31	40 (27%)	109	0.993 (1.00)	0.889 (1.00)	0.0603 (1.00)	0.0921 (1.00)	0.142 (1.00)	0.644 (1.00)	0.576 (1.00)	0.235 (1.00)
del 10q24 33	39 (26%)	110	0.267 (1.00)	0.612 (1.00)	0.217 (1.00)	0.236 (1.00)	0.131 (1.00)	0.921 (1.00)	0.705 (1.00)	0.2 (1.00)
del 11q14 1	26 (17%)	123	0.791 (1.00)	0.268 (1.00)	0.419 (1.00)	0.446 (1.00)	0.058 (1.00)	0.885 (1.00)	0.665 (1.00)	0.34 (1.00)
del 11q23 3	30 (20%)	119	0.714 (1.00)	0.295 (1.00)	0.555 (1.00)	0.462 (1.00)	0.0826 (1.00)	0.9 (1.00)	0.836 (1.00)	0.411 (1.00)
del 12p12 1	33 (22%)	116	0.0729 (1.00)	0.463 (1.00)	0.398 (1.00)	0.842 (1.00)	0.111 (1.00)	0.828 (1.00)	0.841 (1.00)	0.297 (1.00)
del 12q24 33	24 (16%)	125	0.272 (1.00)	0.37 (1.00)	0.0519 (1.00)	0.152 (1.00)	1 (1.00)	0.308 (1.00)	0.821 (1.00)	0.912 (1.00)
del 13q12 11	47 (32%)	102	0.814 (1.00)	0.855 (1.00)	0.0358 (1.00)	0.00821 (1.00)	1 (1.00)	0.0422 (1.00)	0.589 (1.00)	0.585 (1.00)
del 13q22 2	54 (36%)	95	0.935 (1.00)	0.258 (1.00)	0.283 (1.00)	0.00168 (0.753)	0.55 (1.00)	0.345 (1.00)	0.221 (1.00)	0.816 (1.00)
del 14q23 3	51 (34%)	98	0.936 (1.00)	0.987 (1.00)	0.512 (1.00)	0.279 (1.00)	1 (1.00)	0.591 (1.00)	0.86 (1.00)	0.269 (1.00)
del 14q32 33	52 (35%)	97	0.457 (1.00)	0.68 (1.00)	0.498 (1.00)	0.25 (1.00)	1 (1.00)	0.474 (1.00)	1 (1.00)	0.749 (1.00)
del 16q23 1	62 (42%)	87	0.102 (1.00)	0.138 (1.00)	0.34 (1.00)	0.188 (1.00)	0.576 (1.00)	0.93 (1.00)	0.61 (1.00)	0.554 (1.00)
del 17p11 2	79 (53%)	70	0.0917 (1.00)	0.559 (1.00)	0.34 (1.00)	0.2 (1.00)	0.245 (1.00)	1 (1.00)	0.402 (1.00)	0.381 (1.00)
del 19p13 3	32 (21%)	117	0.658 (1.00)	0.795 (1.00)	0.189 (1.00)	0.095 (1.00)	0.511 (1.00)	0.314 (1.00)	0.414 (1.00)	0.928 (1.00)
del 20p12 1	11 (7%)	138	0.317 (1.00)	0.838 (1.00)	0.171 (1.00)	0.737 (1.00)	1 (1.00)	0.191 (1.00)	0.751 (1.00)	0.838 (1.00)
del 22q13 32	41 (28%)	108	0.216 (1.00)	0.412 (1.00)	0.642 (1.00)	0.0816 (1.00)	1 (1.00)	0.36 (1.00)	0.458 (1.00)	0.518 (1.00)

'del_13q14.2' versus 'PATHOLOGY.T.STAGE'

P value = 0.000294 (Fisher's exact test), Q value = 0.13

Table S1. Gene #48: 'del_13q14.2' versus Clinical Feature #4: 'PATHOLOGY.T.STAGE'

nPatients	T1	T2	T3	T4
ALL	61	40	40	8
DEL PEAK 20(13Q14.2) MUTATED	18	26	17	7
DEL PEAK 20(13Q14.2) WILD-TYPE	43	14	23	1

Figure S1. Get High-res Image Gene #48: 'del_13q14.2' versus Clinical Feature #4: 'PATHOLOGY.T.STAGE'

Methods & Data

Input

Copy number data file = transformed.cor.cli.txt
Clinical data file = LIHC-TP.merged_data.txt
Number of patients = 149
Number of significantly focal cnvs = 56
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

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

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

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

[4] 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)

[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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