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

Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (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/C1Q23XVS

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 55 focal events and 9 clinical features across 150 patients, one significant finding detected with Q value < 0.25.

amp_11q22.1 cnv correlated to 'AGE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 55 focal events and 9 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	PATHOLOGY T STAGE	PATHOLOGY N STAGE	PATHOLOGY M STAGE	HISTOLOGICAL TYPE	RADIATIONS RADIATION REGIMENINDICATION	NUMBERPACKYEARSSMOKED	NUMBER OF LYMPH NODES
	nCNV (%)	nWild-Type	logrank test	t-test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Chi-square test	Fisher's exact test	t-test	t-test
amp 11q22 1	27 (18%)	123	0.302 (1.00)	6.86e-05 (0.0339)	0.606 (1.00)	1 (1.00)	0.71 (1.00)	0.713 (1.00)	0.399 (1.00)	0.0313 (1.00)	0.624 (1.00)
amp 1p31 3	49 (33%)	101	0.765 (1.00)	0.0818 (1.00)	0.656 (1.00)	0.381 (1.00)	0.693 (1.00)	0.189 (1.00)	1 (1.00)	0.879 (1.00)	0.35 (1.00)
amp 1q21 3	81 (54%)	69	0.187 (1.00)	0.865 (1.00)	0.211 (1.00)	0.309 (1.00)	0.244 (1.00)	0.877 (1.00)	0.38 (1.00)	0.843 (1.00)	0.892 (1.00)
amp 2p24 3	35 (23%)	115	0.64 (1.00)	0.818 (1.00)	1 (1.00)	0.467 (1.00)	0.825 (1.00)	0.318 (1.00)	0.442 (1.00)	0.258 (1.00)	0.483 (1.00)
amp 2q33 1	25 (17%)	125	0.543 (1.00)	0.613 (1.00)	0.754 (1.00)	0.349 (1.00)	0.426 (1.00)	0.73 (1.00)	0.769 (1.00)	0.57 (1.00)	0.693 (1.00)
amp 3q26 31	114 (76%)	36	0.637 (1.00)	0.423 (1.00)	0.245 (1.00)	0.0388 (1.00)	0.601 (1.00)	0.149 (1.00)	0.0422 (1.00)	0.657 (1.00)	0.0019 (0.931)
amp 3q28	113 (75%)	37	0.407 (1.00)	0.149 (1.00)	0.487 (1.00)	0.0715 (1.00)	0.193 (1.00)	0.0196 (1.00)	0.132 (1.00)	0.843 (1.00)	0.0176 (1.00)
amp 5p15 33	65 (43%)	85	0.824 (1.00)	0.872 (1.00)	0.518 (1.00)	1 (1.00)	0.416 (1.00)	0.0553 (1.00)	0.271 (1.00)	0.538 (1.00)	0.451 (1.00)
amp 6p21 33	44 (29%)	106	0.978 (1.00)	0.65 (1.00)	0.817 (1.00)	1 (1.00)	0.107 (1.00)	0.786 (1.00)	0.811 (1.00)	0.764 (1.00)	0.472 (1.00)
amp 7p11 2	25 (17%)	125	0.425 (1.00)	0.997 (1.00)	0.0681 (1.00)	0.152 (1.00)	1 (1.00)	0.565 (1.00)	0.137 (1.00)	0.848 (1.00)	0.453 (1.00)
amp 8q24 21	61 (41%)	89	0.974 (1.00)	0.118 (1.00)	0.671 (1.00)	1 (1.00)	0.809 (1.00)	0.481 (1.00)	0.661 (1.00)	0.0961 (1.00)	0.181 (1.00)
amp 9p24 1	29 (19%)	121	0.0812 (1.00)	0.95 (1.00)	0.273 (1.00)	0.0335 (1.00)	1 (1.00)	0.646 (1.00)	0.166 (1.00)	0.11 (1.00)	0.422 (1.00)
amp 11p13	11 (7%)	139	0.038 (1.00)	0.533 (1.00)	0.0529 (1.00)	0.598 (1.00)	1 (1.00)	0.922 (1.00)	0.394 (1.00)	0.0239 (1.00)	0.344 (1.00)
amp 11q13 3	19 (13%)	131	0.533 (1.00)	0.127 (1.00)	1 (1.00)	0.543 (1.00)	0.526 (1.00)	0.145 (1.00)	0.0929 (1.00)	0.0746 (1.00)	0.371 (1.00)
amp 13q22 1	32 (21%)	118	0.197 (1.00)	0.816 (1.00)	1 (1.00)	0.292 (1.00)	0.605 (1.00)	0.829 (1.00)	0.599 (1.00)	0.0635 (1.00)	0.0168 (1.00)
amp 13q34	32 (21%)	118	0.634 (1.00)	0.119 (1.00)	1 (1.00)	1 (1.00)	0.815 (1.00)	0.941 (1.00)	0.599 (1.00)	0.103 (1.00)	0.268 (1.00)
amp 15q26 1	33 (22%)	117	0.357 (1.00)	0.878 (1.00)	0.187 (1.00)	0.618 (1.00)	1 (1.00)	0.31 (1.00)	0.794 (1.00)	0.113 (1.00)	0.998 (1.00)
amp 16p13 13	30 (20%)	120	0.636 (1.00)	0.519 (1.00)	0.117 (1.00)	0.206 (1.00)	0.513 (1.00)	0.765 (1.00)	0.589 (1.00)	0.149 (1.00)	0.331 (1.00)
amp 17q12	25 (17%)	125	0.945 (1.00)	0.45 (1.00)	0.245 (1.00)	0.152 (1.00)	0.891 (1.00)	0.362 (1.00)	1 (1.00)	0.481 (1.00)	0.195 (1.00)
amp 17q25 1	39 (26%)	111	0.437 (1.00)	0.85 (1.00)	0.153 (1.00)	0.151 (1.00)	0.856 (1.00)	0.814 (1.00)	0.619 (1.00)	0.349 (1.00)	0.178 (1.00)
amp 19q13 2	45 (30%)	105	0.0504 (1.00)	0.426 (1.00)	0.0941 (1.00)	0.352 (1.00)	0.727 (1.00)	0.53 (1.00)	0.0534 (1.00)	0.86 (1.00)	0.879 (1.00)
amp 20q11 21	62 (41%)	88	0.719 (1.00)	0.26 (1.00)	0.83 (1.00)	0.14 (1.00)	0.416 (1.00)	0.535 (1.00)	0.826 (1.00)	0.464 (1.00)	0.488 (1.00)
amp xq28	39 (26%)	111	0.0167 (1.00)	0.746 (1.00)	0.633 (1.00)	0.238 (1.00)	0.34 (1.00)	0.254 (1.00)	0.317 (1.00)	0.817 (1.00)	0.214 (1.00)
del 1p36 31	22 (15%)	128	0.861 (1.00)	0.162 (1.00)	1 (1.00)	1 (1.00)	0.311 (1.00)	0.244 (1.00)	0.371 (1.00)	0.127 (1.00)	0.364 (1.00)
del 2q22 1	26 (17%)	124	0.278 (1.00)	0.722 (1.00)	0.597 (1.00)	1 (1.00)	0.722 (1.00)	0.47 (1.00)	0.148 (1.00)	0.0429 (1.00)	0.508 (1.00)
del 2q37 1	58 (39%)	92	0.918 (1.00)	0.152 (1.00)	0.0874 (1.00)	1 (1.00)	0.547 (1.00)	0.254 (1.00)	1 (1.00)	0.746 (1.00)	0.619 (1.00)
del 3p14 2	64 (43%)	86	0.455 (1.00)	0.482 (1.00)	0.83 (1.00)	0.02 (1.00)	0.547 (1.00)	0.00157 (0.771)	0.0757 (1.00)	0.309 (1.00)	0.53 (1.00)
del 4q21 3	43 (29%)	107	0.0214 (1.00)	0.312 (1.00)	1 (1.00)	0.0202 (1.00)	0.652 (1.00)	0.183 (1.00)	0.467 (1.00)	0.301 (1.00)	0.221 (1.00)
del 4q35 2	51 (34%)	99	0.111 (1.00)	0.296 (1.00)	0.361 (1.00)	0.5 (1.00)	0.406 (1.00)	0.0456 (1.00)	1 (1.00)	0.131 (1.00)	0.98 (1.00)
del 5q13 3	44 (29%)	106	0.294 (1.00)	0.374 (1.00)	0.245 (1.00)	0.645 (1.00)	0.467 (1.00)	0.182 (1.00)	0.0315 (1.00)	0.559 (1.00)	0.408 (1.00)
del 5q35 2	44 (29%)	106	0.639 (1.00)	0.233 (1.00)	0.487 (1.00)	0.653 (1.00)	0.793 (1.00)	0.185 (1.00)	0.0937 (1.00)	0.631 (1.00)	0.366 (1.00)
del 6p24 2	18 (12%)	132	0.656 (1.00)	0.539 (1.00)	0.754 (1.00)	0.0283 (1.00)	0.426 (1.00)	0.82 (1.00)	0.739 (1.00)	0.482 (1.00)	0.549 (1.00)
del 6q26	51 (34%)	99	0.158 (1.00)	0.477 (1.00)	1 (1.00)	0.261 (1.00)	1 (1.00)	0.506 (1.00)	0.645 (1.00)	0.0232 (1.00)	0.143 (1.00)
del 7q34	37 (25%)	113	0.0289 (1.00)	0.199 (1.00)	0.612 (1.00)	0.0763 (1.00)	0.106 (1.00)	0.842 (1.00)	0.0213 (1.00)	0.485 (1.00)	0.0952 (1.00)
del 8p23 3	51 (34%)	99	0.538 (1.00)	0.687 (1.00)	0.824 (1.00)	0.825 (1.00)	0.737 (1.00)	0.174 (1.00)	0.256 (1.00)	0.668 (1.00)	0.88 (1.00)
del 10q23 31	43 (29%)	107	0.0147 (1.00)	0.0209 (1.00)	0.474 (1.00)	0.0628 (1.00)	0.251 (1.00)	0.83 (1.00)	0.467 (1.00)	0.156 (1.00)	0.257 (1.00)
del 11p15 1	48 (32%)	102	0.505 (1.00)	0.0797 (1.00)	0.824 (1.00)	1 (1.00)	0.595 (1.00)	0.217 (1.00)	0.815 (1.00)	0.893 (1.00)	0.509 (1.00)
del 11q25	88 (59%)	62	0.824 (1.00)	0.0357 (1.00)	1 (1.00)	0.837 (1.00)	0.67 (1.00)	0.0047 (1.00)	0.0743 (1.00)	0.88 (1.00)	0.333 (1.00)
del 13q12 12	55 (37%)	95	0.0891 (1.00)	0.807 (1.00)	0.656 (1.00)	0.0866 (1.00)	1 (1.00)	0.168 (1.00)	0.256 (1.00)	0.192 (1.00)	0.344 (1.00)
del 13q14 2	58 (39%)	92	0.0362 (1.00)	0.0704 (1.00)	0.829 (1.00)	0.292 (1.00)	1 (1.00)	0.0387 (1.00)	0.369 (1.00)	0.202 (1.00)	0.544 (1.00)
del 14q32 31	24 (16%)	126	0.192 (1.00)	0.0101 (1.00)	0.561 (1.00)	0.255 (1.00)	0.885 (1.00)	0.254 (1.00)	0.37 (1.00)	0.662 (1.00)	0.0161 (1.00)
del 15q21 1	32 (21%)	118	0.732 (1.00)	0.0789 (1.00)	0.612 (1.00)	0.219 (1.00)	0.831 (1.00)	0.284 (1.00)	0.599 (1.00)	0.287 (1.00)	0.683 (1.00)
del 16q12 1	28 (19%)	122	0.541 (1.00)	0.0705 (1.00)	0.605 (1.00)	0.0849 (1.00)	0.481 (1.00)	0.00649 (1.00)	0.415 (1.00)	0.8 (1.00)	0.871 (1.00)
del 16q23 1	27 (18%)	123	0.101 (1.00)	0.0858 (1.00)	0.597 (1.00)	0.797 (1.00)	0.896 (1.00)	0.000594 (0.293)	1 (1.00)	0.249 (1.00)	0.563 (1.00)
del 17p12	51 (34%)	99	0.299 (1.00)	0.0378 (1.00)	0.649 (1.00)	1 (1.00)	0.543 (1.00)	0.255 (1.00)	0.256 (1.00)	0.882 (1.00)	0.392 (1.00)
del 17q25 3	26 (17%)	124	0.0803 (1.00)	0.346 (1.00)	0.79 (1.00)	1 (1.00)	0.696 (1.00)	0.253 (1.00)	1 (1.00)	0.973 (1.00)	0.242 (1.00)
del 18q21 2	42 (28%)	108	0.936 (1.00)	0.911 (1.00)	0.473 (1.00)	0.243 (1.00)	0.719 (1.00)	0.00921 (1.00)	1 (1.00)	0.707 (1.00)	0.712 (1.00)
del 19p13 3	47 (31%)	103	0.0405 (1.00)	0.514 (1.00)	0.174 (1.00)	1 (1.00)	0.733 (1.00)	0.357 (1.00)	0.348 (1.00)	0.477 (1.00)	0.98 (1.00)
del 19q13 33	17 (11%)	133	0.354 (1.00)	0.481 (1.00)	0.215 (1.00)	0.539 (1.00)	0.491 (1.00)	0.78 (1.00)	1 (1.00)		0.672 (1.00)
del 20p12 1	19 (13%)	131	0.163 (1.00)	0.726 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.85 (1.00)	0.741 (1.00)	0.174 (1.00)	0.445 (1.00)
del 21q21 1	26 (17%)	124	0.0445 (1.00)	0.953 (1.00)	0.291 (1.00)	0.31 (1.00)	0.564 (1.00)	0.573 (1.00)	0.57 (1.00)	0.264 (1.00)	0.269 (1.00)
del 22q13 32	38 (25%)	112	0.281 (1.00)	0.414 (1.00)	1 (1.00)	0.339 (1.00)	0.525 (1.00)	0.352 (1.00)	0.0792 (1.00)	0.284 (1.00)	0.896 (1.00)
del xp21 1	37 (25%)	113	0.301 (1.00)	0.838 (1.00)	0.47 (1.00)	0.481 (1.00)	0.639 (1.00)	0.182 (1.00)	0.8 (1.00)	0.214 (1.00)	0.297 (1.00)
del xp11 3	40 (27%)	110	0.431 (1.00)	0.831 (1.00)	0.344 (1.00)	0.501 (1.00)	0.392 (1.00)	0.165 (1.00)	0.62 (1.00)	0.135 (1.00)	0.248 (1.00)
del xq21 33	29 (19%)	121	0.0286 (1.00)	0.584 (1.00)	0.605 (1.00)	1 (1.00)	0.245 (1.00)	0.576 (1.00)	0.268 (1.00)	0.566 (1.00)	0.877 (1.00)

'amp_11q22.1' versus 'AGE'

P value = 6.86e-05 (t-test), Q value = 0.034

Table S1. Gene #14: 'amp_11q22.1' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	149	47.4 (13.3)
AMP PEAK 14(11Q22.1) MUTATED	27	39.3 (10.0)
AMP PEAK 14(11Q22.1) WILD-TYPE	122	49.2 (13.3)

Figure S1. Get High-res Image Gene #14: 'amp_11q22.1' versus Clinical Feature #2: 'AGE'

Methods & Data

Input

Copy number data file = transformed.cor.cli.txt
Clinical data file = CESC-TP.merged_data.txt
Number of patients = 150
Number of significantly focal cnvs = 55
Number of selected clinical features = 9
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

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

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

[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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