Correlation between gene mutation status and selected clinical features

Prostate 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 gene mutation status and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1WM1BV2

Overview

Introduction

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

Summary

Testing the association between mutation status of 6 genes and 14 clinical features across 171 patients, 3 significant findings detected with Q value < 0.25.

CTNNB1 mutation correlated to 'NUMBER.OF.LYMPH.NODES'.
PTEN mutation correlated to 'NUMBER.OF.LYMPH.NODES'.
FOXA1 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 6 genes and 14 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 3 significant findings detected.


		Clinical Features	Time to Death	AGE	PATHOLOGY T STAGE	PATHOLOGY N STAGE	COMPLETENESS OF RESECTION	NUMBER OF LYMPH NODES	GLEASON SCORE COMBINED	GLEASON SCORE PRIMARY	GLEASON SCORE SECONDARY	GLEASON SCORE	PSA RESULT PREOP	DAYS TO PREOP PSA	PSA VALUE	DAYS TO PSA
	nMutated (%)	nWild-Type	logrank test	t-test	Fisher's exact test	Fisher's exact test	Fisher's exact test	t-test	t-test	t-test	t-test	t-test	t-test	t-test	t-test	t-test
CTNNB1	4 (2%)	167	100 (1.00)	0.892 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.00109 (0.0915)	0.366 (1.00)	0.902 (1.00)	0.155 (1.00)	0.401 (1.00)	0.0552 (1.00)	0.726 (1.00)	0.769 (1.00)	0.798 (1.00)
PTEN	9 (5%)	162	100 (1.00)	0.411 (1.00)	0.385 (1.00)	1 (1.00)	1 (1.00)	0.00109 (0.0915)	0.896 (1.00)	0.451 (1.00)	0.623 (1.00)	0.756 (1.00)	0.821 (1.00)	0.611 (1.00)	0.492 (1.00)	0.106 (1.00)
FOXA1	6 (4%)	165	100 (1.00)	0.621 (1.00)	0.745 (1.00)	1 (1.00)	0.633 (1.00)	0.00109 (0.0915)	0.637 (1.00)	0.869 (1.00)	0.72 (1.00)	0.49 (1.00)	0.392 (1.00)	0.428 (1.00)	0.565 (1.00)	0.434 (1.00)
SPOP	12 (7%)	159	100 (1.00)	0.0444 (1.00)	0.757 (1.00)	1 (1.00)	1 (1.00)	0.52 (1.00)	0.664 (1.00)	0.163 (1.00)	0.509 (1.00)	0.815 (1.00)	0.468 (1.00)	0.374 (1.00)	0.0305 (1.00)	0.107 (1.00)
PCDHAC2	19 (11%)	152	100 (1.00)	0.417 (1.00)	0.384 (1.00)	0.00323 (0.262)	0.129 (1.00)	0.0918 (1.00)	0.231 (1.00)	0.918 (1.00)	0.155 (1.00)	0.0504 (1.00)	0.219 (1.00)	0.443 (1.00)	0.664 (1.00)	0.853 (1.00)
TP53	15 (9%)	156	100 (1.00)	0.927 (1.00)	0.281 (1.00)	0.66 (1.00)	0.785 (1.00)	0.963 (1.00)	0.0138 (1.00)	0.0195 (1.00)	0.208 (1.00)	0.00439 (0.351)	0.145 (1.00)	0.364 (1.00)	0.983 (1.00)	0.155 (1.00)

'CTNNB1 MUTATION STATUS' versus 'NUMBER.OF.LYMPH.NODES'

P value = 0.00109 (t-test), Q value = 0.092

Table S1. Gene #1: 'CTNNB1 MUTATION STATUS' versus Clinical Feature #6: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	150	0.2 (0.7)
CTNNB1 MUTATED	4	0.0 (0.0)
CTNNB1 WILD-TYPE	146	0.2 (0.7)

Figure S1. Get High-res Image Gene #1: 'CTNNB1 MUTATION STATUS' versus Clinical Feature #6: 'NUMBER.OF.LYMPH.NODES'

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

P value = 0.00109 (t-test), Q value = 0.092

Table S2. Gene #3: 'PTEN MUTATION STATUS' versus Clinical Feature #6: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	150	0.2 (0.7)
PTEN MUTATED	8	0.0 (0.0)
PTEN WILD-TYPE	142	0.2 (0.7)

Figure S2. Get High-res Image Gene #3: 'PTEN MUTATION STATUS' versus Clinical Feature #6: 'NUMBER.OF.LYMPH.NODES'

'FOXA1 MUTATION STATUS' versus 'NUMBER.OF.LYMPH.NODES'

P value = 0.00109 (t-test), Q value = 0.092

Table S3. Gene #5: 'FOXA1 MUTATION STATUS' versus Clinical Feature #6: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	150	0.2 (0.7)
FOXA1 MUTATED	5	0.0 (0.0)
FOXA1 WILD-TYPE	145	0.2 (0.7)

Figure S3. Get High-res Image Gene #5: 'FOXA1 MUTATION STATUS' versus Clinical Feature #6: 'NUMBER.OF.LYMPH.NODES'

Methods & Data

Input

Mutation data file = transformed.cor.cli.txt
Clinical data file = PRAD-TP.merged_data.txt
Number of patients = 171
Number of significantly mutated genes = 6
Number of selected clinical features = 14
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

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] 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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