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

Maintained by TCGA GDAC Team (Broad Institute/Dana-Farber Cancer Institute/Harvard Medical School)

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 71 arm-level results and 8 clinical features across 131 patients, one significant finding detected with Q value < 0.25.

1p gain cnv correlated to 'HISTOLOGICAL.TYPE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 71 arm-level results 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	GENDER	HISTOLOGICAL TYPE	PATHOLOGY T	PATHOLOGY N	PATHOLOGICSPREAD(M)	NEOADJUVANT THERAPY
	nCNV (%)	nWild-Type	logrank test	t-test	Fisher's exact test	Chi-square test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test
1p gain	5 (4%)	126		0.91 (1.00)	0.648 (1.00)	0.000193 (0.107)	1 (1.00)	0.843 (1.00)	0.215 (1.00)	0.243 (1.00)
1q gain	13 (10%)	118	0.282 (1.00)	0.636 (1.00)	0.768 (1.00)	0.222 (1.00)	0.941 (1.00)	0.919 (1.00)	0.239 (1.00)	0.0215 (1.00)
2p gain	8 (6%)	123	0.803 (1.00)	0.412 (1.00)	1 (1.00)	0.807 (1.00)	0.312 (1.00)	0.346 (1.00)	0.682 (1.00)	1 (1.00)
2q gain	8 (6%)	123	0.571 (1.00)	0.896 (1.00)	0.714 (1.00)	0.768 (1.00)	0.702 (1.00)	0.203 (1.00)	0.157 (1.00)	1 (1.00)
3p gain	6 (5%)	125		0.265 (1.00)	0.4 (1.00)	0.95 (1.00)	0.0984 (1.00)	0.77 (1.00)	1 (1.00)	1 (1.00)
3q gain	13 (10%)	118	0.334 (1.00)	0.0981 (1.00)	0.239 (1.00)	0.0979 (1.00)	0.0126 (1.00)	0.964 (1.00)	0.316 (1.00)	0.528 (1.00)
5p gain	25 (19%)	106	0.59 (1.00)	0.664 (1.00)	0.0726 (1.00)	0.308 (1.00)	0.909 (1.00)	0.388 (1.00)	0.653 (1.00)	0.127 (1.00)
5q gain	6 (5%)	125	0.0703 (1.00)	0.95 (1.00)	1 (1.00)	0.00205 (1.00)	0.544 (1.00)	0.152 (1.00)	0.573 (1.00)	1 (1.00)
6p gain	8 (6%)	123	0.804 (1.00)	0.822 (1.00)	0.714 (1.00)	0.889 (1.00)	0.126 (1.00)	0.65 (1.00)	0.682 (1.00)	1 (1.00)
6q gain	6 (5%)	125		0.365 (1.00)	0.221 (1.00)	0.894 (1.00)	0.312 (1.00)	0.656 (1.00)	1 (1.00)	1 (1.00)
7p gain	39 (30%)	92	0.763 (1.00)	0.201 (1.00)	0.847 (1.00)	0.115 (1.00)	0.609 (1.00)	0.414 (1.00)	1 (1.00)	0.424 (1.00)
7q gain	30 (23%)	101	0.769 (1.00)	0.0399 (1.00)	1 (1.00)	0.401 (1.00)	0.613 (1.00)	0.464 (1.00)	0.402 (1.00)	0.659 (1.00)
8p gain	39 (30%)	92	0.716 (1.00)	0.0239 (1.00)	0.0197 (1.00)	0.347 (1.00)	0.475 (1.00)	0.0363 (1.00)	0.177 (1.00)	1 (1.00)
8q gain	52 (40%)	79	0.894 (1.00)	0.00313 (1.00)	0.101 (1.00)	0.426 (1.00)	0.048 (1.00)	0.0136 (1.00)	0.0609 (1.00)	1 (1.00)
9p gain	10 (8%)	121	0.591 (1.00)	0.932 (1.00)	0.525 (1.00)	0.756 (1.00)	0.103 (1.00)	0.0853 (1.00)	0.472 (1.00)	0.434 (1.00)
9q gain	9 (7%)	122	0.542 (1.00)	0.617 (1.00)	0.484 (1.00)	0.986 (1.00)	0.101 (1.00)	0.26 (1.00)	0.423 (1.00)	0.4 (1.00)
10p gain	16 (12%)	115	0.134 (1.00)	0.582 (1.00)	0.427 (1.00)	0.912 (1.00)	0.0633 (1.00)	0.113 (1.00)	0.32 (1.00)	1 (1.00)
10q gain	7 (5%)	124	0.952 (1.00)	0.217 (1.00)	0.701 (1.00)	0.941 (1.00)	0.0265 (1.00)	0.683 (1.00)	0.631 (1.00)	0.325 (1.00)
11p gain	7 (5%)	124	0.23 (1.00)	0.232 (1.00)	1 (1.00)	0.874 (1.00)	0.262 (1.00)	0.0335 (1.00)	1 (1.00)	1 (1.00)
11q gain	8 (6%)	123	0.218 (1.00)	0.36 (1.00)	0.714 (1.00)	0.394 (1.00)	0.109 (1.00)	0.132 (1.00)	1 (1.00)	0.364 (1.00)
12p gain	13 (10%)	118	0.873 (1.00)	0.336 (1.00)	0.559 (1.00)	0.984 (1.00)	0.451 (1.00)	0.865 (1.00)	0.753 (1.00)	1 (1.00)
12q gain	9 (7%)	122	0.641 (1.00)	0.148 (1.00)	0.739 (1.00)	0.154 (1.00)	0.0394 (1.00)	0.908 (1.00)	1 (1.00)	0.4 (1.00)
13q gain	27 (21%)	104	0.534 (1.00)	0.279 (1.00)	1 (1.00)	0.0917 (1.00)	0.595 (1.00)	0.021 (1.00)	1 (1.00)	0.633 (1.00)
14q gain	4 (3%)	127		0.576 (1.00)	0.025 (1.00)	0.941 (1.00)			0.0816 (1.00)	1 (1.00)
16p gain	10 (8%)	121	0.882 (1.00)	0.0537 (1.00)	1 (1.00)	0.072 (1.00)	0.00701 (1.00)	0.0358 (1.00)	0.472 (1.00)	0.00969 (1.00)
16q gain	5 (4%)	126	0.96 (1.00)	0.326 (1.00)	0.394 (1.00)	0.516 (1.00)	0.00176 (0.975)	0.656 (1.00)	0.126 (1.00)	0.243 (1.00)
17p gain	5 (4%)	126	0.0178 (1.00)	0.778 (1.00)	1 (1.00)	0.854 (1.00)	0.312 (1.00)	0.0141 (1.00)	0.0137 (1.00)	1 (1.00)
17q gain	10 (8%)	121	0.0234 (1.00)	0.219 (1.00)	1 (1.00)	0.891 (1.00)	0.283 (1.00)	0.0461 (1.00)	0.0155 (1.00)	1 (1.00)
18p gain	17 (13%)	114	0.852 (1.00)	0.609 (1.00)	0.602 (1.00)	0.514 (1.00)	0.487 (1.00)	0.583 (1.00)	0.532 (1.00)	0.225 (1.00)
18q gain	10 (8%)	121	0.715 (1.00)	0.72 (1.00)	0.315 (1.00)	0.756 (1.00)	0.394 (1.00)	0.756 (1.00)	0.134 (1.00)	1 (1.00)
19p gain	9 (7%)	122	0.403 (1.00)	0.424 (1.00)	0.157 (1.00)	0.099 (1.00)	1 (1.00)	0.0134 (1.00)	0.423 (1.00)	0.0738 (1.00)
19q gain	16 (12%)	115	0.46 (1.00)	0.604 (1.00)	0.0631 (1.00)	0.487 (1.00)	0.892 (1.00)	0.374 (1.00)	0.124 (1.00)	0.204 (1.00)
20p gain	47 (36%)	84	0.281 (1.00)	0.322 (1.00)	0.0671 (1.00)	0.549 (1.00)	0.507 (1.00)	0.559 (1.00)	0.233 (1.00)	0.249 (1.00)
20q gain	63 (48%)	68	0.0527 (1.00)	0.906 (1.00)	0.0744 (1.00)	0.0798 (1.00)	0.893 (1.00)	0.241 (1.00)	0.835 (1.00)	0.26 (1.00)
22q gain	3 (2%)	128		0.198 (1.00)	1 (1.00)	0.0565 (1.00)			1 (1.00)	0.153 (1.00)
1p loss	11 (8%)	120	0.868 (1.00)	0.951 (1.00)	0.351 (1.00)	0.84 (1.00)	0.0763 (1.00)	0.3 (1.00)	0.00335 (1.00)	1 (1.00)
1q loss	5 (4%)	126	0.665 (1.00)	0.0419 (1.00)	0.394 (1.00)	0.369 (1.00)	0.573 (1.00)	0.502 (1.00)	0.126 (1.00)	1 (1.00)
3p loss	9 (7%)	122	0.596 (1.00)	0.948 (1.00)	0.157 (1.00)	0.858 (1.00)	0.25 (1.00)	0.788 (1.00)	0.423 (1.00)	0.4 (1.00)
3q loss	3 (2%)	128	0.736 (1.00)	0.828 (1.00)	1 (1.00)	0.455 (1.00)	0.429 (1.00)	0.247 (1.00)	1 (1.00)	1 (1.00)
4p loss	20 (15%)	111	0.727 (1.00)	0.1 (1.00)	0.145 (1.00)	0.384 (1.00)	0.459 (1.00)	0.958 (1.00)	0.842 (1.00)	1 (1.00)
4q loss	18 (14%)	113	0.755 (1.00)	0.945 (1.00)	0.305 (1.00)	0.0498 (1.00)	0.429 (1.00)	0.843 (1.00)	1 (1.00)	1 (1.00)
5p loss	9 (7%)	122	0.403 (1.00)	0.701 (1.00)	0.739 (1.00)	0.183 (1.00)	0.874 (1.00)	0.557 (1.00)	0.697 (1.00)	1 (1.00)
5q loss	17 (13%)	114	0.502 (1.00)	0.703 (1.00)	0.43 (1.00)	0.00288 (1.00)	0.0287 (1.00)	0.95 (1.00)	0.332 (1.00)	1 (1.00)
6p loss	10 (8%)	121	0.844 (1.00)	0.0529 (1.00)	0.525 (1.00)	0.168 (1.00)	0.921 (1.00)	0.0162 (1.00)	0.323 (1.00)	0.434 (1.00)
6q loss	7 (5%)	124	0.432 (1.00)	0.0857 (1.00)	0.701 (1.00)	0.968 (1.00)	0.544 (1.00)	0.424 (1.00)	0.122 (1.00)	0.325 (1.00)
7p loss	3 (2%)	128	0.216 (1.00)	0.264 (1.00)	0.272 (1.00)	0.136 (1.00)	0.0323 (1.00)	0.843 (1.00)	1 (1.00)	1 (1.00)
7q loss	6 (5%)	125	0.112 (1.00)	0.979 (1.00)	1 (1.00)	0.214 (1.00)	0.0313 (1.00)	0.767 (1.00)	0.573 (1.00)	1 (1.00)
8p loss	16 (12%)	115	0.476 (1.00)	0.0901 (1.00)	1 (1.00)	0.0602 (1.00)	0.293 (1.00)	0.435 (1.00)	0.32 (1.00)	0.597 (1.00)
8q loss	4 (3%)	127		0.579 (1.00)	0.647 (1.00)	0.607 (1.00)	1 (1.00)		1 (1.00)	1 (1.00)
9p loss	27 (21%)	104	0.0873 (1.00)	0.358 (1.00)	1 (1.00)	0.0151 (1.00)	0.15 (1.00)	0.746 (1.00)	0.569 (1.00)	0.633 (1.00)
9q loss	16 (12%)	115	0.363 (1.00)	0.207 (1.00)	0.588 (1.00)	0.901 (1.00)	0.0752 (1.00)	0.95 (1.00)	0.804 (1.00)	1 (1.00)
10p loss	11 (8%)	120	0.149 (1.00)	0.892 (1.00)	1 (1.00)	0.489 (1.00)	0.234 (1.00)	0.474 (1.00)	1 (1.00)	1 (1.00)
10q loss	10 (8%)	121	0.151 (1.00)	0.424 (1.00)	1 (1.00)	0.68 (1.00)	0.508 (1.00)	0.719 (1.00)	1 (1.00)	1 (1.00)
11p loss	17 (13%)	114	0.216 (1.00)	0.434 (1.00)	0.793 (1.00)	0.898 (1.00)	0.127 (1.00)	0.758 (1.00)	0.145 (1.00)	0.594 (1.00)
11q loss	13 (10%)	118	0.308 (1.00)	0.166 (1.00)	0.559 (1.00)	0.858 (1.00)	0.228 (1.00)	0.735 (1.00)	0.166 (1.00)	1 (1.00)
12p loss	11 (8%)	120	0.376 (1.00)	0.863 (1.00)	0.524 (1.00)	0.176 (1.00)	0.204 (1.00)	0.0175 (1.00)	0.721 (1.00)	1 (1.00)
12q loss	7 (5%)	124	0.581 (1.00)	0.457 (1.00)	0.0411 (1.00)	0.82 (1.00)	0.273 (1.00)	0.269 (1.00)	1 (1.00)	1 (1.00)
13q loss	6 (5%)	125	0.801 (1.00)	0.602 (1.00)	1 (1.00)	0.119 (1.00)	0.106 (1.00)	0.0406 (1.00)	0.573 (1.00)	0.285 (1.00)
14q loss	9 (7%)	122	0.581 (1.00)	0.169 (1.00)	0.739 (1.00)	0.986 (1.00)	0.425 (1.00)	0.841 (1.00)	0.697 (1.00)	1 (1.00)
15q loss	10 (8%)	121	0.455 (1.00)	0.0388 (1.00)	0.739 (1.00)	0.00829 (1.00)	0.0458 (1.00)	0.423 (1.00)	1 (1.00)	0.434 (1.00)
16p loss	8 (6%)	123	0.568 (1.00)	0.377 (1.00)	0.142 (1.00)	0.102 (1.00)	0.152 (1.00)	0.707 (1.00)	0.682 (1.00)	1 (1.00)
16q loss	12 (9%)	119	0.549 (1.00)	0.977 (1.00)	0.359 (1.00)	0.0787 (1.00)	0.351 (1.00)	0.232 (1.00)	1 (1.00)	1 (1.00)
17p loss	26 (20%)	105	0.165 (1.00)	0.0583 (1.00)	0.372 (1.00)	0.00384 (1.00)	0.203 (1.00)	0.045 (1.00)	0.484 (1.00)	0.14 (1.00)
17q loss	9 (7%)	122	0.749 (1.00)	0.472 (1.00)	0.484 (1.00)	0.00137 (0.761)	0.921 (1.00)	0.63 (1.00)	0.423 (1.00)	0.4 (1.00)
18p loss	12 (9%)	119	0.398 (1.00)	0.56 (1.00)	0.761 (1.00)	0.448 (1.00)	0.142 (1.00)	0.386 (1.00)	1 (1.00)	0.125 (1.00)
18q loss	26 (20%)	105	0.687 (1.00)	0.45 (1.00)	0.656 (1.00)	0.244 (1.00)	0.253 (1.00)	0.334 (1.00)	0.484 (1.00)	0.0286 (1.00)
19p loss	16 (12%)	115	0.473 (1.00)	0.927 (1.00)	0.1 (1.00)	0.351 (1.00)	0.182 (1.00)	0.356 (1.00)	1 (1.00)	1 (1.00)
19q loss	8 (6%)	123	0.238 (1.00)	0.499 (1.00)	0.142 (1.00)	0.267 (1.00)	0.0227 (1.00)	0.14 (1.00)	1 (1.00)	1 (1.00)
20p loss	6 (5%)	125	0.126 (1.00)	0.903 (1.00)	0.221 (1.00)	0.708 (1.00)	0.632 (1.00)	0.707 (1.00)	0.573 (1.00)	1 (1.00)
21q loss	25 (19%)	106	0.264 (1.00)	0.722 (1.00)	0.498 (1.00)	0.213 (1.00)	1 (1.00)	0.153 (1.00)	0.039 (1.00)	0.618 (1.00)
22q loss	18 (14%)	113	0.67 (1.00)	0.207 (1.00)	1 (1.00)	0.226 (1.00)	0.722 (1.00)	0.569 (1.00)	0.445 (1.00)	0.592 (1.00)

'1p gain mutation analysis' versus 'HISTOLOGICAL.TYPE'

P value = 0.000193 (Chi-square test), Q value = 0.11

Table S1. Gene #1: '1p gain mutation analysis' versus Clinical Feature #4: 'HISTOLOGICAL.TYPE'

nPatients	STOMACH ADENOCARCINOMA - DIFFUSE TYPE	STOMACH ADENOCARCINOMA - NOT OTHERWISE SPECIFIED (NOS)	STOMACH INTESTINAL ADENOCARCINOMA - MUCINOUS TYPE	STOMACH INTESTINAL ADENOCARCINOMA - PAPILLARY TYPE	STOMACH INTESTINAL ADENOCARCINOMA - TUBULAR TYPE	STOMACH INTESTINAL ADENOCARCINOMA - TYPE NOT OTHERWISE SPECIFIED (NOS)
ALL	13	73	4	2	10	24
1P GAIN MUTATED	0	3	2	0	0	0
1P GAIN WILD-TYPE	13	70	2	2	10	24

Figure S1. Get High-res Image Gene #1: '1p gain mutation analysis' versus Clinical Feature #4: 'HISTOLOGICAL.TYPE'

Methods & Data

Input

Mutation data file = broad_values_by_arm.mutsig.cluster.txt
Clinical data file = STAD.clin.merged.picked.txt
Number of patients = 131
Number of significantly arm-level cnvs = 71
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

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

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] 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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