Correlation between copy number variations of arm-level result and selected clinical features

Pancreatic Adenocarcinoma (Primary solid tumor)

15 January 2014 | analyses__2014_01_15

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 variations of arm-level result and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1668BM7

Overview

Introduction

This pipeline computes the correlation between significant arm-level copy number variations (cnvs) and selected clinical features.

Summary

Testing the association between copy number variation 61 arm-level events and 12 clinical features across 57 patients, 5 significant findings detected with Q value < 0.25.

3p gain cnv correlated to 'Time to Death'.
5q gain cnv correlated to 'AGE'.
17q gain cnv correlated to 'Time to Death'.
22q gain cnv correlated to 'Time to Death'.
20p loss 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 61 arm-level events and 12 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	NEOPLASM DISEASESTAGE	PATHOLOGY T STAGE	PATHOLOGY N STAGE	PATHOLOGY M STAGE	GENDER	HISTOLOGICAL TYPE	NUMBERPACKYEARSSMOKED	YEAROFTOBACCOSMOKINGONSET	COMPLETENESS OF RESECTION	NUMBER OF LYMPH NODES
	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	t-test	t-test	Fisher's exact test	t-test
3p gain	3 (5%)	54	8.5e-05 (0.0537)	0.0281 (1.00)	0.895 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.587 (1.00)	1 (1.00)			1 (1.00)	0.904 (1.00)
5q gain	3 (5%)	54		5.25e-05 (0.0332)	0.895 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.587 (1.00)	1 (1.00)			0.603 (1.00)	0.438 (1.00)
17q gain	3 (5%)	54	8.5e-05 (0.0537)	0.835 (1.00)	0.895 (1.00)	1 (1.00)	1 (1.00)	0.333 (1.00)	0.587 (1.00)	1 (1.00)				0.771 (1.00)
22q gain	3 (5%)	54	9.36e-05 (0.059)	0.895 (1.00)	0.895 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)				0.744 (1.00)
20p loss	4 (7%)	53	9.22e-09 (5.84e-06)	0.813 (1.00)	0.892 (1.00)	0.367 (1.00)	0.563 (1.00)	0.394 (1.00)	1 (1.00)	0.32 (1.00)			0.0294 (1.00)	0.961 (1.00)
1p gain	3 (5%)	54		0.82 (1.00)	0.941 (1.00)	1 (1.00)	0.568 (1.00)	0.61 (1.00)	0.587 (1.00)	1 (1.00)			1 (1.00)	0.891 (1.00)
1q gain	12 (21%)	45	0.705 (1.00)	0.827 (1.00)	0.679 (1.00)	0.325 (1.00)	1 (1.00)	0.211 (1.00)	0.117 (1.00)	0.659 (1.00)	0.184 (1.00)	0.14 (1.00)	1 (1.00)	0.973 (1.00)
2p gain	6 (11%)	51	0.642 (1.00)	0.368 (1.00)	0.623 (1.00)	1 (1.00)	0.629 (1.00)	0.0657 (1.00)	0.396 (1.00)	1 (1.00)	0.261 (1.00)	0.281 (1.00)	0.484 (1.00)	0.586 (1.00)
2q gain	7 (12%)	50	0.3 (1.00)	0.563 (1.00)	0.702 (1.00)	1 (1.00)	1 (1.00)	0.0548 (1.00)	0.228 (1.00)	1 (1.00)	0.261 (1.00)	0.281 (1.00)	0.366 (1.00)	0.919 (1.00)
3q gain	7 (12%)	50	0.102 (1.00)	0.436 (1.00)	0.453 (1.00)	0.562 (1.00)	0.346 (1.00)	0.321 (1.00)	0.691 (1.00)	1 (1.00)			0.556 (1.00)	0.385 (1.00)
4p gain	3 (5%)	54		0.849 (1.00)	0.117 (1.00)	1 (1.00)	1 (1.00)	0.0192 (1.00)	0.242 (1.00)	1 (1.00)			1 (1.00)	0.218 (1.00)
4q gain	3 (5%)	54		0.849 (1.00)	0.117 (1.00)	1 (1.00)	1 (1.00)	0.0192 (1.00)	0.242 (1.00)	1 (1.00)			1 (1.00)	0.218 (1.00)
5p gain	5 (9%)	52	0.681 (1.00)	0.0559 (1.00)	0.947 (1.00)	1 (1.00)	1 (1.00)	0.7 (1.00)	0.651 (1.00)	0.385 (1.00)			0.294 (1.00)	0.246 (1.00)
7p gain	13 (23%)	44	0.921 (1.00)	0.941 (1.00)	0.685 (1.00)	0.319 (1.00)	1 (1.00)	0.234 (1.00)	0.22 (1.00)	1 (1.00)			0.00396 (1.00)	0.908 (1.00)
7q gain	12 (21%)	45	0.8 (1.00)	0.842 (1.00)	0.647 (1.00)	0.325 (1.00)	0.71 (1.00)	0.211 (1.00)	0.349 (1.00)	1 (1.00)			0.0102 (1.00)	0.643 (1.00)
8p gain	8 (14%)	49	0.00145 (0.909)	0.573 (1.00)	0.269 (1.00)	0.58 (1.00)	0.391 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)			0.556 (1.00)	0.522 (1.00)
8q gain	15 (26%)	42	0.469 (1.00)	0.629 (1.00)	0.677 (1.00)	1 (1.00)	0.486 (1.00)	0.56 (1.00)	0.236 (1.00)	1 (1.00)			0.3 (1.00)	0.89 (1.00)
9q gain	3 (5%)	54	0.0262 (1.00)	0.881 (1.00)	0.118 (1.00)	1 (1.00)	0.146 (1.00)	0.333 (1.00)	0.0889 (1.00)	1 (1.00)			0.603 (1.00)	0.725 (1.00)
11p gain	6 (11%)	51	0.671 (1.00)	0.779 (1.00)	0.623 (1.00)	1 (1.00)	0.629 (1.00)	0.507 (1.00)	0.396 (1.00)	1 (1.00)			0.116 (1.00)	0.496 (1.00)
11q gain	6 (11%)	51	0.458 (1.00)	0.157 (1.00)	0.623 (1.00)	1 (1.00)	0.629 (1.00)	0.507 (1.00)	0.396 (1.00)	1 (1.00)			0.484 (1.00)	0.353 (1.00)
12p gain	6 (11%)	51	0.174 (1.00)	0.223 (1.00)	0.653 (1.00)	0.504 (1.00)	1 (1.00)	0.38 (1.00)	0.0828 (1.00)	0.0836 (1.00)			0.14 (1.00)	0.651 (1.00)
12q gain	5 (9%)	52	0.0343 (1.00)	0.366 (1.00)	0.83 (1.00)	1 (1.00)	0.319 (1.00)	0.293 (1.00)	0.167 (1.00)	0.0579 (1.00)			0.0612 (1.00)	0.37 (1.00)
13q gain	4 (7%)	53	0.302 (1.00)	0.987 (1.00)	0.892 (1.00)	1 (1.00)	0.563 (1.00)	1 (1.00)	0.617 (1.00)	0.32 (1.00)			0.347 (1.00)	0.799 (1.00)
14q gain	7 (12%)	50	0.968 (1.00)	0.459 (1.00)	0.439 (1.00)	1 (1.00)	0.669 (1.00)	0.253 (1.00)	1 (1.00)	1 (1.00)			0.366 (1.00)	0.93 (1.00)
15q gain	4 (7%)	53	0.0168 (1.00)	0.121 (1.00)	0.892 (1.00)	1 (1.00)	0.563 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)			1 (1.00)	0.218 (1.00)
16p gain	6 (11%)	51	0.797 (1.00)	0.274 (1.00)	0.307 (1.00)	0.504 (1.00)	0.151 (1.00)	0.141 (1.00)	0.0828 (1.00)	0.445 (1.00)			0.0266 (1.00)	0.0836 (1.00)
16q gain	7 (12%)	50	0.949 (1.00)	0.231 (1.00)	0.453 (1.00)	0.562 (1.00)	0.346 (1.00)	0.123 (1.00)	0.228 (1.00)	0.501 (1.00)			0.0629 (1.00)	0.229 (1.00)
18p gain	6 (11%)	51	0.674 (1.00)	0.339 (1.00)	0.512 (1.00)	1 (1.00)	0.629 (1.00)	0.259 (1.00)	0.396 (1.00)	0.445 (1.00)			0.14 (1.00)	0.0258 (1.00)
19p gain	3 (5%)	54	0.897 (1.00)	0.549 (1.00)	0.941 (1.00)	1 (1.00)	0.568 (1.00)	0.333 (1.00)	0.587 (1.00)	1 (1.00)				0.0958 (1.00)
19q gain	6 (11%)	51	0.59 (1.00)	0.792 (1.00)	0.407 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.396 (1.00)	1 (1.00)	0.0417 (1.00)	0.455 (1.00)	1 (1.00)	0.446 (1.00)
20p gain	10 (18%)	47	0.342 (1.00)	0.0483 (1.00)	0.855 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.16 (1.00)	0.641 (1.00)			0.106 (1.00)	0.771 (1.00)
20q gain	11 (19%)	46	0.342 (1.00)	0.0289 (1.00)	0.833 (1.00)	1 (1.00)	0.714 (1.00)	0.835 (1.00)	0.0891 (1.00)	1 (1.00)			0.214 (1.00)	0.308 (1.00)
1p loss	7 (12%)	50	0.359 (1.00)	0.103 (1.00)	0.913 (1.00)	1 (1.00)	0.669 (1.00)	0.4 (1.00)	0.691 (1.00)	1 (1.00)	0.393 (1.00)	0.057 (1.00)	0.556 (1.00)	0.314 (1.00)
2p loss	6 (11%)	51	0.434 (1.00)	0.663 (1.00)	0.936 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.445 (1.00)			0.14 (1.00)	0.504 (1.00)
3p loss	11 (19%)	46	0.62 (1.00)	0.554 (1.00)	0.821 (1.00)	1 (1.00)	1 (1.00)	0.563 (1.00)	0.0155 (1.00)	1 (1.00)	0.261 (1.00)		0.149 (1.00)	0.227 (1.00)
3q loss	5 (9%)	52	0.564 (1.00)	0.434 (1.00)	0.493 (1.00)	1 (1.00)	0.587 (1.00)	0.491 (1.00)	0.0157 (1.00)	1 (1.00)			0.484 (1.00)	0.278 (1.00)
4p loss	6 (11%)	51	0.171 (1.00)	0.066 (1.00)	0.936 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.0828 (1.00)	1 (1.00)			0.366 (1.00)	0.484 (1.00)
4q loss	5 (9%)	52	0.952 (1.00)	0.00953 (1.00)	0.947 (1.00)	1 (1.00)	1 (1.00)	0.7 (1.00)	0.0157 (1.00)	1 (1.00)			0.116 (1.00)	0.832 (1.00)
5q loss	5 (9%)	52	0.9 (1.00)	0.4 (1.00)	0.83 (1.00)	1 (1.00)	0.319 (1.00)	0.7 (1.00)	0.651 (1.00)	0.385 (1.00)			0.0979 (1.00)	0.399 (1.00)
6p loss	20 (35%)	37	0.182 (1.00)	0.636 (1.00)	0.568 (1.00)	0.41 (1.00)	0.53 (1.00)	0.0855 (1.00)	0.164 (1.00)	0.737 (1.00)	0.973 (1.00)	0.362 (1.00)	0.39 (1.00)	0.825 (1.00)
6q loss	23 (40%)	34	0.649 (1.00)	0.492 (1.00)	0.357 (1.00)	0.385 (1.00)	0.532 (1.00)	0.0184 (1.00)	0.794 (1.00)	0.783 (1.00)	0.969 (1.00)	0.528 (1.00)	0.553 (1.00)	0.73 (1.00)
8p loss	8 (14%)	49	0.708 (1.00)	0.501 (1.00)	0.431 (1.00)	1 (1.00)	1 (1.00)	0.352 (1.00)	0.448 (1.00)	0.501 (1.00)			0.158 (1.00)	0.59 (1.00)
9p loss	22 (39%)	35	0.173 (1.00)	0.951 (1.00)	0.171 (1.00)	0.389 (1.00)	0.0556 (1.00)	0.324 (1.00)	1 (1.00)	1 (1.00)	0.324 (1.00)	0.102 (1.00)	0.155 (1.00)	0.0667 (1.00)
9q loss	12 (21%)	45	0.395 (1.00)	0.596 (1.00)	0.636 (1.00)	1 (1.00)	0.258 (1.00)	0.708 (1.00)	1 (1.00)	1 (1.00)			0.7 (1.00)	0.155 (1.00)
10p loss	10 (18%)	47	0.159 (1.00)	0.236 (1.00)	0.275 (1.00)	0.281 (1.00)	0.694 (1.00)	0.278 (1.00)	0.486 (1.00)	0.641 (1.00)	0.624 (1.00)	0.439 (1.00)	0.395 (1.00)	0.972 (1.00)
10q loss	10 (18%)	47	0.295 (1.00)	0.209 (1.00)	0.855 (1.00)	1 (1.00)	1 (1.00)	0.278 (1.00)	0.486 (1.00)	0.641 (1.00)	0.16 (1.00)		0.395 (1.00)	0.32 (1.00)
11p loss	5 (9%)	52	0.646 (1.00)	0.527 (1.00)	0.947 (1.00)	1 (1.00)	1 (1.00)	0.111 (1.00)	0.651 (1.00)	1 (1.00)			1 (1.00)	0.596 (1.00)
11q loss	4 (7%)	53	0.519 (1.00)	0.769 (1.00)	0.94 (1.00)	1 (1.00)	1 (1.00)	0.682 (1.00)	0.322 (1.00)	0.32 (1.00)			0.159 (1.00)	0.338 (1.00)
12p loss	6 (11%)	51	0.458 (1.00)	0.796 (1.00)	0.221 (1.00)	1 (1.00)	0.151 (1.00)	0.0251 (1.00)	0.396 (1.00)	1 (1.00)			0.0629 (1.00)	0.121 (1.00)
12q loss	7 (12%)	50	0.274 (1.00)	0.496 (1.00)	0.453 (1.00)	0.562 (1.00)	0.346 (1.00)	0.0217 (1.00)	0.691 (1.00)	1 (1.00)	0.261 (1.00)		0.176 (1.00)	0.102 (1.00)
13q loss	9 (16%)	48	0.922 (1.00)	0.343 (1.00)	0.439 (1.00)	0.575 (1.00)	0.427 (1.00)	0.189 (1.00)	0.275 (1.00)	0.262 (1.00)	0.393 (1.00)	0.681 (1.00)	0.106 (1.00)	0.277 (1.00)
15q loss	8 (14%)	49	0.829 (1.00)	0.642 (1.00)	0.35 (1.00)	1 (1.00)	0.391 (1.00)	0.0827 (1.00)	0.124 (1.00)	0.501 (1.00)			0.556 (1.00)	0.109 (1.00)
17p loss	20 (35%)	37	0.293 (1.00)	0.368 (1.00)	0.173 (1.00)	0.0809 (1.00)	0.749 (1.00)	0.199 (1.00)	0.781 (1.00)	0.737 (1.00)	0.168 (1.00)	0.111 (1.00)	0.000825 (0.519)	0.623 (1.00)
17q loss	9 (16%)	48	0.81 (1.00)	0.734 (1.00)	0.679 (1.00)	0.575 (1.00)	1 (1.00)	0.315 (1.00)	0.275 (1.00)	0.144 (1.00)			0.0427 (1.00)	0.133 (1.00)
18p loss	21 (37%)	36	0.912 (1.00)	0.072 (1.00)	0.264 (1.00)	0.659 (1.00)	0.751 (1.00)	1 (1.00)	0.789 (1.00)	0.77 (1.00)	0.258 (1.00)	0.863 (1.00)	0.301 (1.00)	0.839 (1.00)
18q loss	30 (53%)	27	0.424 (1.00)	0.678 (1.00)	0.273 (1.00)	1 (1.00)	1 (1.00)	0.329 (1.00)	0.431 (1.00)	0.799 (1.00)	0.582 (1.00)	0.206 (1.00)	0.03 (1.00)	0.512 (1.00)
19p loss	6 (11%)	51	0.993 (1.00)	0.91 (1.00)	0.407 (1.00)	1 (1.00)	1 (1.00)	0.259 (1.00)	0.678 (1.00)	1 (1.00)			0.74 (1.00)	0.45 (1.00)
19q loss	5 (9%)	52	0.993 (1.00)	0.934 (1.00)	0.342 (1.00)	1 (1.00)	1 (1.00)	0.165 (1.00)	1 (1.00)	1 (1.00)			0.484 (1.00)	0.484 (1.00)
21q loss	19 (33%)	38	0.303 (1.00)	0.234 (1.00)	0.0999 (1.00)	0.164 (1.00)	0.109 (1.00)	0.054 (1.00)	0.407 (1.00)	1 (1.00)	0.651 (1.00)	0.537 (1.00)	0.0374 (1.00)	0.1 (1.00)
22q loss	9 (16%)	48	0.416 (1.00)	0.773 (1.00)	0.553 (1.00)	0.575 (1.00)	0.674 (1.00)	0.189 (1.00)	0.00797 (1.00)	0.552 (1.00)			0.0518 (1.00)	0.538 (1.00)
xq loss	3 (5%)	54	0.313 (1.00)	0.383 (1.00)	0.941 (1.00)	1 (1.00)	0.568 (1.00)	0.333 (1.00)	1 (1.00)	1 (1.00)			1 (1.00)	0.594 (1.00)

'3p gain' versus 'Time to Death'

P value = 8.5e-05 (logrank test), Q value = 0.054

Table S1. Gene #5: '3p gain' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	54	19	0.0 - 49.4 (5.6)
3P GAIN MUTATED	3	2	0.1 - 4.8 (3.9)
3P GAIN WILD-TYPE	51	17	0.0 - 49.4 (7.1)

Figure S1. Get High-res Image Gene #5: '3p gain' versus Clinical Feature #1: 'Time to Death'

'5q gain' versus 'AGE'

P value = 5.25e-05 (t-test), Q value = 0.033

Table S2. Gene #10: '5q gain' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	57	66.2 (10.4)
5Q GAIN MUTATED	3	77.7 (2.1)
5Q GAIN WILD-TYPE	54	65.5 (10.3)

Figure S2. Get High-res Image Gene #10: '5q gain' versus Clinical Feature #2: 'AGE'

'17q gain' versus 'Time to Death'

P value = 8.5e-05 (logrank test), Q value = 0.054

Table S3. Gene #25: '17q gain' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	54	19	0.0 - 49.4 (5.6)
17Q GAIN MUTATED	3	2	0.0 - 4.8 (3.9)
17Q GAIN WILD-TYPE	51	17	0.1 - 49.4 (7.1)

Figure S3. Get High-res Image Gene #25: '17q gain' versus Clinical Feature #1: 'Time to Death'

'22q gain' versus 'Time to Death'

P value = 9.36e-05 (logrank test), Q value = 0.059

Table S4. Gene #31: '22q gain' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	54	19	0.0 - 49.4 (5.6)
22Q GAIN MUTATED	3	1	0.0 - 3.9 (0.1)
22Q GAIN WILD-TYPE	51	18	0.1 - 49.4 (7.1)

Figure S4. Get High-res Image Gene #31: '22q gain' versus Clinical Feature #1: 'Time to Death'

'20p loss' versus 'Time to Death'

P value = 9.22e-09 (logrank test), Q value = 5.8e-06

Table S5. Gene #58: '20p loss' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	54	19	0.0 - 49.4 (5.6)
20P LOSS MUTATED	3	1	0.8 - 3.6 (1.5)
20P LOSS WILD-TYPE	51	18	0.0 - 49.4 (7.1)

Figure S5. Get High-res Image Gene #58: '20p loss' versus Clinical Feature #1: 'Time to Death'

Methods & Data

Input

Copy number data file = transformed.cor.cli.txt
Clinical data file = PAAD-TP.merged_data.txt
Number of patients = 57
Number of significantly arm-level cnvs = 61
Number of selected clinical features = 12
Exclude regions 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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