Correlation between gene mutation status and selected clinical features

Prostate Adenocarcinoma (Primary solid tumor)

17 October 2014 | analyses__2014_10_17

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 gene mutation status and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C12Z14F6

Overview

Introduction

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

Summary

Testing the association between mutation status of 37 genes and 13 clinical features across 256 patients, 2 significant findings detected with Q value < 0.25.

TP53 mutation correlated to 'GLEASON_SCORE_COMBINED' and 'GLEASON_SCORE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 37 genes and 13 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 2 significant findings detected.


		Clinical Features	AGE	PATHOLOGY T STAGE	PATHOLOGY N STAGE	HISTOLOGICAL TYPE	COMPLETENESS OF RESECTION	NUMBER OF LYMPH NODES	GLEASON SCORE COMBINED	GLEASON SCORE PRIMARY	GLEASON SCORE SECONDARY	GLEASON SCORE	PSA RESULT PREOP	PSA VALUE	RACE
	nMutated (%)	nWild-Type	Wilcoxon-test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Wilcoxon-test	Wilcoxon-test	Wilcoxon-test	Wilcoxon-test	Wilcoxon-test	Wilcoxon-test	Wilcoxon-test	Fisher's exact test
TP53	22 (9%)	234	0.719 (1.00)	0.325 (1.00)	0.714 (1.00)	1 (1.00)	0.712 (1.00)	0.69 (1.00)	0.000281 (0.128)	0.00405 (1.00)	0.0688 (1.00)	9.9e-05 (0.0452)	0.274 (1.00)	0.0929 (1.00)	1 (1.00)
SPOP	26 (10%)	230	0.158 (1.00)	0.816 (1.00)	1 (1.00)	0.115 (1.00)	0.728 (1.00)	0.802 (1.00)	0.7 (1.00)	0.344 (1.00)	0.693 (1.00)	0.913 (1.00)	0.819 (1.00)	0.908 (1.00)	0.554 (1.00)
PTEN	12 (5%)	244	0.752 (1.00)	1 (1.00)	0.337 (1.00)	0.252 (1.00)	0.427 (1.00)	0.401 (1.00)	0.323 (1.00)	0.704 (1.00)	0.397 (1.00)	0.429 (1.00)	0.384 (1.00)	0.0103 (1.00)	1 (1.00)
CTNNB1	9 (4%)	247	0.507 (1.00)	0.426 (1.00)	0.603 (1.00)	0.195 (1.00)	0.779 (1.00)	0.318 (1.00)	0.52 (1.00)	0.823 (1.00)	0.438 (1.00)	0.34 (1.00)	0.0753 (1.00)	0.457 (1.00)	1 (1.00)
TCEB3	4 (2%)	252	0.551 (1.00)	0.652 (1.00)	0.291 (1.00)	1 (1.00)	1 (1.00)	0.245 (1.00)	0.179 (1.00)	0.14 (1.00)	0.667 (1.00)	0.217 (1.00)	0.418 (1.00)	0.657 (1.00)
FOXA1	12 (5%)	244	0.193 (1.00)	0.4 (1.00)	0.602 (1.00)	1 (1.00)	0.488 (1.00)	0.288 (1.00)	0.698 (1.00)	0.654 (1.00)	0.6 (1.00)	0.556 (1.00)	0.982 (1.00)	0.344 (1.00)	0.0524 (1.00)
BRAF	5 (2%)	251	0.817 (1.00)	0.435 (1.00)	1 (1.00)	0.113 (1.00)	1 (1.00)	0.487 (1.00)	0.922 (1.00)	0.227 (1.00)	0.208 (1.00)	0.994 (1.00)	0.347 (1.00)	0.738 (1.00)
PIK3CA	9 (4%)	247	0.289 (1.00)	0.592 (1.00)	0.556 (1.00)	0.195 (1.00)	0.0399 (1.00)	0.816 (1.00)	0.0411 (1.00)	0.292 (1.00)	0.0894 (1.00)	0.0652 (1.00)	0.652 (1.00)	0.443 (1.00)	1 (1.00)
IDH1	4 (2%)	252	0.0177 (1.00)	0.655 (1.00)	0.369 (1.00)	1 (1.00)	0.0833 (1.00)	0.405 (1.00)	0.0104 (1.00)	0.0523 (1.00)	0.0519 (1.00)	0.0142 (1.00)	0.0773 (1.00)	0.32 (1.00)
FAM47C	8 (3%)	248	0.55 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.778 (1.00)	0.39 (1.00)	0.107 (1.00)	0.932 (1.00)	0.0333 (1.00)	0.24 (1.00)	0.66 (1.00)	0.885 (1.00)	1 (1.00)
TP53BP1	5 (2%)	251	0.453 (1.00)	0.436 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.549 (1.00)	0.0812 (1.00)	0.0778 (1.00)	0.7 (1.00)	0.11 (1.00)	0.944 (1.00)	0.407 (1.00)
CNTNAP1	5 (2%)	251	0.654 (1.00)	1 (1.00)	1 (1.00)	0.113 (1.00)	0.336 (1.00)	0.549 (1.00)	0.131 (1.00)	0.723 (1.00)	0.0612 (1.00)	0.488 (1.00)	0.708 (1.00)	0.788 (1.00)
MLLT10	4 (2%)	252	0.166 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.646 (1.00)	0.487 (1.00)	0.767 (1.00)	0.673 (1.00)	0.566 (1.00)	0.846 (1.00)	0.643 (1.00)	0.126 (1.00)	1 (1.00)
ZMYM3	5 (2%)	251	0.505 (1.00)	0.438 (1.00)	0.438 (1.00)	1 (1.00)	0.191 (1.00)	0.556 (1.00)	0.0481 (1.00)	0.178 (1.00)	0.0814 (1.00)	0.0644 (1.00)	0.175 (1.00)	0.175 (1.00)	1 (1.00)
SMG7	4 (2%)	252	0.657 (1.00)	0.654 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.487 (1.00)	0.767 (1.00)	0.954 (1.00)	0.667 (1.00)	0.846 (1.00)	0.234 (1.00)	0.225 (1.00)	1 (1.00)
EDC4	3 (1%)	253	0.328 (1.00)	1 (1.00)	0.291 (1.00)	1 (1.00)	1 (1.00)	0.245 (1.00)	0.521 (1.00)	0.623 (1.00)	0.652 (1.00)	0.47 (1.00)	0.187 (1.00)	0.444 (1.00)	0.166 (1.00)
ZNF709	4 (2%)	252	0.493 (1.00)	0.193 (1.00)	1 (1.00)	1 (1.00)	0.132 (1.00)	0.487 (1.00)	0.278 (1.00)	0.0495 (1.00)	0.695 (1.00)	0.217 (1.00)	0.45 (1.00)	0.647 (1.00)
CDK12	7 (3%)	249	0.7 (1.00)	1 (1.00)	0.501 (1.00)	0.155 (1.00)	0.395 (1.00)	0.611 (1.00)	0.0727 (1.00)	0.243 (1.00)	0.286 (1.00)	0.107 (1.00)	0.385 (1.00)	0.751 (1.00)
RPTN	6 (2%)	250	0.364 (1.00)	0.486 (1.00)	1 (1.00)	1 (1.00)	0.137 (1.00)	0.435 (1.00)	0.219 (1.00)	0.393 (1.00)	0.556 (1.00)	0.198 (1.00)	0.523 (1.00)	0.13 (1.00)	0.163 (1.00)
TNRC18	4 (2%)	252	0.866 (1.00)	0.654 (1.00)	0.369 (1.00)	1 (1.00)	0.186 (1.00)	0.291 (1.00)	0.767 (1.00)	0.954 (1.00)	0.667 (1.00)	0.846 (1.00)	0.643 (1.00)	0.785 (1.00)
MED15	5 (2%)	251	0.518 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.435 (1.00)	0.0579 (1.00)	0.0778 (1.00)	0.259 (1.00)	0.0789 (1.00)	0.439 (1.00)	0.236 (1.00)	0.164 (1.00)
NKX3-1	5 (2%)	251	0.387 (1.00)	0.261 (1.00)	1 (1.00)	1 (1.00)	0.669 (1.00)	0.435 (1.00)	0.405 (1.00)	0.622 (1.00)	0.114 (1.00)	0.112 (1.00)	0.787 (1.00)	0.776 (1.00)	1 (1.00)
KDM6A	6 (2%)	250	0.338 (1.00)	0.0194 (1.00)	1 (1.00)	1 (1.00)	0.14 (1.00)	0.39 (1.00)	0.955 (1.00)	0.138 (1.00)	0.204 (1.00)	0.663 (1.00)	0.617 (1.00)	0.397 (1.00)	1 (1.00)
RNF31	4 (2%)	252	0.456 (1.00)	0.652 (1.00)	1 (1.00)	1 (1.00)	0.13 (1.00)	0.487 (1.00)	0.179 (1.00)	0.312 (1.00)	0.265 (1.00)	0.217 (1.00)	0.646 (1.00)	0.785 (1.00)
ESCO1	4 (2%)	252	0.291 (1.00)	0.657 (1.00)	1 (1.00)	1 (1.00)	0.588 (1.00)	0.487 (1.00)	0.767 (1.00)	0.375 (1.00)	0.208 (1.00)	0.846 (1.00)	0.567 (1.00)	0.416 (1.00)	1 (1.00)
LMOD2	3 (1%)	253	0.282 (1.00)	0.621 (1.00)	1 (1.00)	1 (1.00)			0.534 (1.00)	0.623 (1.00)	0.652 (1.00)	0.493 (1.00)	0.0855 (1.00)	0.367 (1.00)
FAM120B	3 (1%)	253	0.997 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)		0.521 (1.00)	0.55 (1.00)	0.159 (1.00)	0.47 (1.00)	0.658 (1.00)	0.785 (1.00)	1 (1.00)
CLEC1A	4 (2%)	252	0.707 (1.00)	0.0774 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.549 (1.00)	0.13 (1.00)	0.375 (1.00)	0.282 (1.00)	0.118 (1.00)	0.915 (1.00)	0.135 (1.00)
RNF17	3 (1%)	253	0.413 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.549 (1.00)	0.521 (1.00)	0.112 (1.00)	0.62 (1.00)	0.47 (1.00)		0.52 (1.00)	1 (1.00)
RP1L1	7 (3%)	249	0.5 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.243 (1.00)	0.435 (1.00)	0.164 (1.00)	0.659 (1.00)	0.0894 (1.00)	0.486 (1.00)	0.143 (1.00)	0.898 (1.00)
EOMES	4 (2%)	252	0.34 (1.00)	0.0773 (1.00)	1 (1.00)	1 (1.00)	0.0832 (1.00)	0.549 (1.00)	0.457 (1.00)	0.601 (1.00)	0.265 (1.00)	0.492 (1.00)	0.482 (1.00)	0.0567 (1.00)
MTF1	3 (1%)	253	0.102 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.589 (1.00)		0.0499 (1.00)	0.257 (1.00)	0.0381 (1.00)	0.00607 (1.00)	0.658 (1.00)	0.215 (1.00)
NTM	5 (2%)	251	0.429 (1.00)	0.435 (1.00)	1 (1.00)	1 (1.00)	0.443 (1.00)	0.435 (1.00)	0.73 (1.00)	0.622 (1.00)	0.7 (1.00)	0.79 (1.00)	0.205 (1.00)	0.311 (1.00)	1 (1.00)
FNBP4	3 (1%)	253	0.718 (1.00)	0.292 (1.00)	0.291 (1.00)	1 (1.00)	0.23 (1.00)	0.245 (1.00)	0.451 (1.00)	0.257 (1.00)	0.742 (1.00)	0.501 (1.00)	0.144 (1.00)
CDKN1B	4 (2%)	252	0.211 (1.00)	0.0777 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.487 (1.00)	0.278 (1.00)	0.312 (1.00)	0.667 (1.00)	0.0464 (1.00)	0.945 (1.00)	0.632 (1.00)	1 (1.00)
EIF2AK3	4 (2%)	252	0.42 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.131 (1.00)		0.971 (1.00)	0.954 (1.00)	0.805 (1.00)	0.846 (1.00)	0.842 (1.00)	0.984 (1.00)	1 (1.00)
LARP1	3 (1%)	253	0.515 (1.00)	1 (1.00)	0.291 (1.00)	1 (1.00)		0.167 (1.00)	0.534 (1.00)	0.623 (1.00)	0.652 (1.00)	0.493 (1.00)	0.902 (1.00)	0.876 (1.00)

'TP53 MUTATION STATUS' versus 'GLEASON_SCORE_COMBINED'

P value = 0.000281 (Wilcoxon-test), Q value = 0.13

Table S1. Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #7: 'GLEASON_SCORE_COMBINED'

	nPatients	Mean (Std.Dev)
ALL	256	7.4 (0.9)
TP53 MUTATED	22	8.0 (0.9)
TP53 WILD-TYPE	234	7.3 (0.8)

Figure S1. Get High-res Image Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #7: 'GLEASON_SCORE_COMBINED'

'TP53 MUTATION STATUS' versus 'GLEASON_SCORE'

P value = 9.9e-05 (Wilcoxon-test), Q value = 0.045

Table S2. Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #10: 'GLEASON_SCORE'

	nPatients	Mean (Std.Dev)
ALL	256	7.4 (0.9)
TP53 MUTATED	22	8.1 (0.9)
TP53 WILD-TYPE	234	7.3 (0.9)

Figure S2. Get High-res Image Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #10: 'GLEASON_SCORE'

Methods & Data

Input

Mutation data file = transformed.cor.cli.txt
Clinical data file = PRAD-TP.merged_data.txt
Number of patients = 256
Number of significantly mutated genes = 37
Number of selected clinical features = 13
Exclude genes that fewer than K tumors have mutations, K = 3

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] 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)

[2] 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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