Correlation between gene mutation status and selected clinical features

Stomach Adenocarcinoma (Primary solid tumor)

21 April 2013 | analyses__2013_04_21

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): Stomach Adenocarcinoma (Primary solid tumor cohort) - 21 April 2013: Correlation between gene mutation status and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C17H1GJR

Overview

Introduction

This pipeline computes the correlation between significantly recurrent gene mutations and selected clinical features.

Summary

Testing the association between mutation status of 47 genes and 10 clinical features across 116 patients, 6 significant findings detected with Q value < 0.25.

HLA-B mutation correlated to 'NUMBER.OF.LYMPH.NODES'.
POTEG mutation correlated to 'NUMBER.OF.LYMPH.NODES'.
TPTE mutation correlated to 'NUMBER.OF.LYMPH.NODES'.
CPS1 mutation correlated to 'NUMBER.OF.LYMPH.NODES'.
INO80E mutation correlated to 'PATHOLOGY.T'.
UPF3A mutation correlated to 'NUMBER.OF.LYMPH.NODES'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 47 genes and 10 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 6 significant findings detected.


		Clinical Features	Time to Death	AGE	GENDER	HISTOLOGICAL TYPE	PATHOLOGY T	PATHOLOGY N	PATHOLOGICSPREAD(M)	TUMOR STAGE	COMPLETENESS OF RESECTION	NUMBER OF LYMPH NODES
	nMutated (%)	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	Fisher's exact test	t-test
HLA-B	9 (8%)	107	0.963 (1.00)	0.717 (1.00)	0.028 (1.00)	0.556 (1.00)	0.126 (1.00)	0.111 (1.00)	0.329 (1.00)	0.303 (1.00)	0.916 (1.00)	1.71e-07 (7.78e-05)
POTEG	6 (5%)	110	0.221 (1.00)	0.0101 (1.00)	0.68 (1.00)	0.568 (1.00)	0.643 (1.00)	0.683 (1.00)	1 (1.00)	0.806 (1.00)	0.309 (1.00)	3.6e-05 (0.0163)
TPTE	14 (12%)	102	0.382 (1.00)	0.92 (1.00)	0.401 (1.00)	0.00396 (1.00)	0.283 (1.00)	0.263 (1.00)	0.505 (1.00)	0.974 (1.00)	0.58 (1.00)	2.59e-06 (0.00118)
CPS1	13 (11%)	103	0.862 (1.00)	0.922 (1.00)	0.24 (1.00)	0.471 (1.00)	0.608 (1.00)	0.526 (1.00)	0.202 (1.00)	0.943 (1.00)	0.233 (1.00)	3.12e-07 (0.000142)
INO80E	5 (4%)	111		0.936 (1.00)	0.0798 (1.00)	0.805 (1.00)	0.000484 (0.218)	0.913 (1.00)	0.554 (1.00)	0.0587 (1.00)	0.0932 (1.00)	0.537 (1.00)
UPF3A	6 (5%)	110	0.647 (1.00)	0.253 (1.00)	0.68 (1.00)	0.86 (1.00)	0.00203 (0.906)	0.789 (1.00)	0.21 (1.00)	0.244 (1.00)	0.511 (1.00)	3.6e-05 (0.0163)
CBWD1	14 (12%)	102	0.303 (1.00)	0.0229 (1.00)	0.243 (1.00)	0.312 (1.00)	0.000583 (0.262)	0.692 (1.00)	0.505 (1.00)	0.264 (1.00)	0.541 (1.00)	0.036 (1.00)
KRAS	14 (12%)	102	0.353 (1.00)	0.496 (1.00)	0.243 (1.00)	0.701 (1.00)	0.8 (1.00)	0.348 (1.00)	0.623 (1.00)	0.41 (1.00)	0.0502 (1.00)	0.147 (1.00)
PGM5	16 (14%)	100	0.962 (1.00)	0.00184 (0.821)	0.0138 (1.00)	0.495 (1.00)	0.00445 (1.00)	0.898 (1.00)	0.555 (1.00)	0.381 (1.00)	0.45 (1.00)	0.773 (1.00)
RPL22	9 (8%)	107	0.478 (1.00)	0.0449 (1.00)	0.48 (1.00)	0.591 (1.00)	0.0528 (1.00)	0.303 (1.00)	0.000925 (0.415)	0.099 (1.00)	0.107 (1.00)	0.00755 (1.00)
TP53	52 (45%)	64	0.0826 (1.00)	0.519 (1.00)	0.345 (1.00)	0.0205 (1.00)	0.754 (1.00)	0.975 (1.00)	0.123 (1.00)	0.747 (1.00)	0.376 (1.00)	0.888 (1.00)
TRIM48	10 (9%)	106	0.322 (1.00)	0.157 (1.00)	0.191 (1.00)	0.448 (1.00)	0.0924 (1.00)	0.698 (1.00)	0.0506 (1.00)	0.241 (1.00)	0.0335 (1.00)	0.022 (1.00)
XPOT	6 (5%)	110		0.238 (1.00)	0.68 (1.00)	0.812 (1.00)	1 (1.00)	0.646 (1.00)	0.114 (1.00)	0.489 (1.00)	0.25 (1.00)
PIK3CA	24 (21%)	92	0.407 (1.00)	0.457 (1.00)	0.253 (1.00)	0.789 (1.00)	0.669 (1.00)	0.655 (1.00)	1 (1.00)	0.375 (1.00)	0.324 (1.00)	0.544 (1.00)
ACVR2A	13 (11%)	103	0.00155 (0.693)	0.218 (1.00)	0.131 (1.00)	0.263 (1.00)	0.128 (1.00)	0.881 (1.00)	0.371 (1.00)	0.414 (1.00)	0.342 (1.00)	0.012 (1.00)
RHOA	7 (6%)	109	0.0968 (1.00)	0.0615 (1.00)	0.701 (1.00)	0.451 (1.00)	0.559 (1.00)	0.765 (1.00)	0.681 (1.00)	0.157 (1.00)	1 (1.00)	0.679 (1.00)
ARID1A	22 (19%)	94	0.225 (1.00)	0.814 (1.00)	0.0525 (1.00)	0.298 (1.00)	0.114 (1.00)	0.422 (1.00)	0.0193 (1.00)	0.168 (1.00)	0.0325 (1.00)	0.77 (1.00)
OR8H3	10 (9%)	106	0.626 (1.00)	0.424 (1.00)	0.738 (1.00)	0.0783 (1.00)	0.774 (1.00)	0.113 (1.00)	0.724 (1.00)	0.688 (1.00)	0.0919 (1.00)	0.444 (1.00)
EDNRB	12 (10%)	104	0.877 (1.00)	0.831 (1.00)	0.537 (1.00)	0.365 (1.00)	0.233 (1.00)	0.339 (1.00)	0.451 (1.00)	0.885 (1.00)	0.283 (1.00)	0.786 (1.00)
ZNF804B	18 (16%)	98	0.909 (1.00)	0.267 (1.00)	0.61 (1.00)	0.416 (1.00)	1 (1.00)	0.13 (1.00)	0.382 (1.00)	0.0243 (1.00)	0.694 (1.00)	0.985 (1.00)
IRF2	8 (7%)	108	0.74 (1.00)	0.234 (1.00)	0.0568 (1.00)	0.762 (1.00)	0.0166 (1.00)	0.873 (1.00)	0.288 (1.00)	0.928 (1.00)	0.0937 (1.00)	0.135 (1.00)
IAPP	4 (3%)	112		0.485 (1.00)	1 (1.00)	0.937 (1.00)	1 (1.00)	0.897 (1.00)	0.189 (1.00)	0.107 (1.00)	0.647 (1.00)	0.0298 (1.00)
PCDH15	22 (19%)	94	0.855 (1.00)	0.534 (1.00)	0.63 (1.00)	0.878 (1.00)	0.407 (1.00)	0.757 (1.00)	0.649 (1.00)	0.222 (1.00)	0.921 (1.00)	0.39 (1.00)
SPRYD5	8 (7%)	108	0.143 (1.00)	0.135 (1.00)	1 (1.00)	0.904 (1.00)	0.0528 (1.00)	0.765 (1.00)	0.103 (1.00)	0.0411 (1.00)	0.538 (1.00)	0.492 (1.00)
TUSC3	9 (8%)	107	0.76 (1.00)	0.28 (1.00)	1 (1.00)	0.783 (1.00)	0.46 (1.00)	0.488 (1.00)	0.329 (1.00)	0.551 (1.00)	0.632 (1.00)	0.222 (1.00)
FGF22	3 (3%)	113		0.0539 (1.00)	0.562 (1.00)	0.712 (1.00)			0.381 (1.00)		0.382 (1.00)
PTH2	3 (3%)	113		0.782 (1.00)	0.562 (1.00)	0.775 (1.00)	0.78 (1.00)	0.377 (1.00)	1 (1.00)	0.687 (1.00)	0.737 (1.00)	0.273 (1.00)
C17ORF63	3 (3%)	113		0.524 (1.00)	0.562 (1.00)	0.836 (1.00)	0.121 (1.00)	0.437 (1.00)	1 (1.00)	0.532 (1.00)	1 (1.00)
SMAD4	7 (6%)	109	0.103 (1.00)	0.051 (1.00)	0.701 (1.00)	0.663 (1.00)	0.9 (1.00)	1 (1.00)	0.153 (1.00)	1 (1.00)	0.0935 (1.00)	0.0418 (1.00)
RNF43	13 (11%)	103	0.0257 (1.00)	0.0612 (1.00)	0.368 (1.00)	0.151 (1.00)	0.062 (1.00)	0.881 (1.00)	0.484 (1.00)	0.185 (1.00)	0.233 (1.00)	0.14 (1.00)
WBSCR17	12 (10%)	104	0.116 (1.00)	0.185 (1.00)	0.537 (1.00)	0.281 (1.00)	0.419 (1.00)	0.965 (1.00)	0.333 (1.00)	0.835 (1.00)	0.893 (1.00)	0.00345 (1.00)
PHF2	12 (10%)	104	0.905 (1.00)	0.017 (1.00)	0.537 (1.00)	0.403 (1.00)	0.0106 (1.00)	0.6 (1.00)	0.00397 (1.00)	0.118 (1.00)	0.308 (1.00)	0.00906 (1.00)
CDH1	11 (9%)	105	0.516 (1.00)	0.137 (1.00)	0.751 (1.00)	0.116 (1.00)	0.565 (1.00)	0.79 (1.00)	1 (1.00)	0.134 (1.00)	0.309 (1.00)	0.565 (1.00)
ELF3	5 (4%)	111	0.541 (1.00)	0.701 (1.00)	0.384 (1.00)	0.402 (1.00)	0.366 (1.00)	0.623 (1.00)	1 (1.00)	0.928 (1.00)	1 (1.00)	0.0887 (1.00)
PARK2	9 (8%)	107	0.73 (1.00)	0.00874 (1.00)	1 (1.00)	0.109 (1.00)	0.292 (1.00)	0.351 (1.00)	0.329 (1.00)	0.199 (1.00)	0.916 (1.00)	0.00642 (1.00)
LARP4B	5 (4%)	111	0.541 (1.00)	0.445 (1.00)	0.384 (1.00)	0.402 (1.00)	0.0286 (1.00)	0.897 (1.00)	1 (1.00)	0.489 (1.00)	0.836 (1.00)	0.221 (1.00)
OR6K3	6 (5%)	110	0.63 (1.00)	0.436 (1.00)	0.212 (1.00)	0.153 (1.00)	0.322 (1.00)	1 (1.00)	0.309 (1.00)	0.147 (1.00)	0.36 (1.00)	0.874 (1.00)
TM7SF4	7 (6%)	109	0.915 (1.00)	0.553 (1.00)	0.701 (1.00)	0.855 (1.00)	0.619 (1.00)	0.847 (1.00)	1 (1.00)	0.676 (1.00)	1 (1.00)	0.281 (1.00)
C7ORF63	5 (4%)	111	0.471 (1.00)	0.42 (1.00)	0.0798 (1.00)	0.322 (1.00)	0.0223 (1.00)	0.646 (1.00)	0.155 (1.00)	0.587 (1.00)	0.0773 (1.00)
KDM4B	10 (9%)	106	0.81 (1.00)	0.0778 (1.00)	0.0136 (1.00)	0.435 (1.00)	0.126 (1.00)	0.847 (1.00)	0.369 (1.00)	0.512 (1.00)	0.189 (1.00)	0.316 (1.00)
KIAA0748	7 (6%)	109	0.337 (1.00)	0.375 (1.00)	1 (1.00)	0.735 (1.00)	0.699 (1.00)	0.568 (1.00)	1 (1.00)	0.199 (1.00)	1 (1.00)	0.807 (1.00)
OR8B4	3 (3%)	113	0.541 (1.00)	0.782 (1.00)	0.562 (1.00)	0.389 (1.00)	0.357 (1.00)	0.082 (1.00)	1 (1.00)	0.292 (1.00)	0.737 (1.00)	0.948 (1.00)
POM121L12	7 (6%)	109	0.943 (1.00)	0.449 (1.00)	1 (1.00)	0.568 (1.00)	0.106 (1.00)	0.769 (1.00)	0.153 (1.00)	0.38 (1.00)	0.429 (1.00)	0.663 (1.00)
RASA1	9 (8%)	107	0.307 (1.00)	0.0831 (1.00)	0.739 (1.00)	0.216 (1.00)	0.0242 (1.00)	0.698 (1.00)	0.0915 (1.00)	0.547 (1.00)	0.216 (1.00)	0.222 (1.00)
SLITRK6	10 (9%)	106	0.231 (1.00)	0.693 (1.00)	0.738 (1.00)	0.742 (1.00)	0.925 (1.00)	0.619 (1.00)	0.26 (1.00)	0.327 (1.00)	0.41 (1.00)	0.143 (1.00)
TP53TG5	4 (3%)	112	0.739 (1.00)	0.758 (1.00)	1 (1.00)	0.048 (1.00)	0.0655 (1.00)	0.404 (1.00)	1 (1.00)	0.489 (1.00)	0.785 (1.00)
LHCGR	7 (6%)	109	0.863 (1.00)	0.369 (1.00)	1 (1.00)	0.808 (1.00)	0.0805 (1.00)	0.442 (1.00)	0.249 (1.00)	0.928 (1.00)	0.174 (1.00)	0.47 (1.00)

'HLA-B MUTATION STATUS' versus 'NUMBER.OF.LYMPH.NODES'

P value = 1.71e-07 (t-test), Q value = 7.8e-05

Table S1. Gene #21: 'HLA-B MUTATION STATUS' versus Clinical Feature #10: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	71	4.5 (6.3)
HLA-B MUTATED	7	0.1 (0.4)
HLA-B WILD-TYPE	64	5.0 (6.5)

Figure S1. Get High-res Image Gene #21: 'HLA-B MUTATION STATUS' versus Clinical Feature #10: 'NUMBER.OF.LYMPH.NODES'

'POTEG MUTATION STATUS' versus 'NUMBER.OF.LYMPH.NODES'

P value = 3.6e-05 (t-test), Q value = 0.016

Table S2. Gene #25: 'POTEG MUTATION STATUS' versus Clinical Feature #10: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	71	4.5 (6.3)
POTEG MUTATED	5	0.8 (0.8)
POTEG WILD-TYPE	66	4.8 (6.5)

Figure S2. Get High-res Image Gene #25: 'POTEG MUTATION STATUS' versus Clinical Feature #10: 'NUMBER.OF.LYMPH.NODES'

'TPTE MUTATION STATUS' versus 'NUMBER.OF.LYMPH.NODES'

P value = 2.59e-06 (t-test), Q value = 0.0012

Table S3. Gene #29: 'TPTE MUTATION STATUS' versus Clinical Feature #10: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	71	4.5 (6.3)
TPTE MUTATED	8	0.6 (0.5)
TPTE WILD-TYPE	63	5.0 (6.6)

Figure S3. Get High-res Image Gene #29: 'TPTE MUTATION STATUS' versus Clinical Feature #10: 'NUMBER.OF.LYMPH.NODES'

'CPS1 MUTATION STATUS' versus 'NUMBER.OF.LYMPH.NODES'

P value = 3.12e-07 (t-test), Q value = 0.00014

Table S4. Gene #31: 'CPS1 MUTATION STATUS' versus Clinical Feature #10: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	71	4.5 (6.3)
CPS1 MUTATED	8	0.2 (0.5)
CPS1 WILD-TYPE	63	5.0 (6.5)

Figure S4. Get High-res Image Gene #31: 'CPS1 MUTATION STATUS' versus Clinical Feature #10: 'NUMBER.OF.LYMPH.NODES'

'INO80E MUTATION STATUS' versus 'PATHOLOGY.T'

P value = 0.000484 (Fisher's exact test), Q value = 0.22

Table S5. Gene #32: 'INO80E MUTATION STATUS' versus Clinical Feature #5: 'PATHOLOGY.T'

nPatients	T1	T2	T3	T4
ALL	4	46	41	15
INO80E MUTATED	0	0	0	4
INO80E WILD-TYPE	4	46	41	11

Figure S5. Get High-res Image Gene #32: 'INO80E MUTATION STATUS' versus Clinical Feature #5: 'PATHOLOGY.T'

'UPF3A MUTATION STATUS' versus 'NUMBER.OF.LYMPH.NODES'

P value = 3.6e-05 (t-test), Q value = 0.016

Table S6. Gene #38: 'UPF3A MUTATION STATUS' versus Clinical Feature #10: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	71	4.5 (6.3)
UPF3A MUTATED	5	0.8 (0.8)
UPF3A WILD-TYPE	66	4.8 (6.5)

Figure S6. Get High-res Image Gene #38: 'UPF3A MUTATION STATUS' versus Clinical Feature #10: 'NUMBER.OF.LYMPH.NODES'

Methods & Data

Input

Mutation data file = STAD-TP.mutsig.cluster.txt
Clinical data file = STAD-TP.clin.merged.picked.txt
Number of patients = 116
Number of significantly mutated genes = 47
Number of selected clinical features = 10
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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