Correlation between mutation rate and clinical features

Prostate Adenocarcinoma (Primary solid tumor)

15 July 2014 | analyses__2014_07_15

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between mutation rate and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1F18XJT

Overview

Introduction

This pipeline uses various statistical tests to identify selected clinical features related to mutation rate.

Summary

Testing the association between 2 variables and 14 clinical features across 247 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 7 clinical features related to at least one variables.

2 variables correlated to 'AGE'.

MUTATIONRATE_NONSYNONYMOUS , MUTATIONRATE_SILENT

1 variable correlated to 'PATHOLOGY.T.STAGE'.

MUTATIONRATE_NONSYNONYMOUS

2 variables correlated to 'GLEASON_SCORE_COMBINED'.

MUTATIONRATE_NONSYNONYMOUS , MUTATIONRATE_SILENT

2 variables correlated to 'GLEASON_SCORE_PRIMARY'.

MUTATIONRATE_NONSYNONYMOUS , MUTATIONRATE_SILENT

2 variables correlated to 'GLEASON_SCORE'.

MUTATIONRATE_NONSYNONYMOUS , MUTATIONRATE_SILENT

2 variables correlated to 'PSA_RESULT_PREOP'.

MUTATIONRATE_SILENT , MUTATIONRATE_NONSYNONYMOUS

2 variables correlated to 'PSA_VALUE'.

MUTATIONRATE_NONSYNONYMOUS , MUTATIONRATE_SILENT

No variables correlated to 'AGE_mutation.rate', 'PATHOLOGY.N.STAGE', 'HISTOLOGICAL.TYPE', 'COMPLETENESS.OF.RESECTION', 'NUMBER.OF.LYMPH.NODES', 'GLEASON_SCORE_SECONDARY', and 'RACE'.

Results

Overview of the results

Complete statistical result table is provided in Supplement Table 1

Table 1. Get Full Table This table shows the clinical features, statistical methods used, and the number of variables that are significantly associated with each clinical feature at P value < 0.05 and Q value < 0.3.

Clinical feature	Statistical test	Significant variables	Associated with		Associated with
AGE	Spearman correlation test	N=2	older	N=2	younger	N=0
AGE	Linear Regression Analysis	N=0
PATHOLOGY T STAGE	Spearman correlation test	N=1	higher stage	N=1	lower stage	N=0
PATHOLOGY N STAGE	Wilcoxon test	N=0
HISTOLOGICAL TYPE	Wilcoxon test	N=0
COMPLETENESS OF RESECTION	Kruskal-Wallis test	N=0
NUMBER OF LYMPH NODES	Spearman correlation test	N=0
GLEASON_SCORE_COMBINED	Spearman correlation test	N=2	higher score	N=2	lower score	N=0
GLEASON_SCORE_PRIMARY	Spearman correlation test	N=2	higher score	N=2	lower score	N=0
GLEASON_SCORE_SECONDARY	Spearman correlation test	N=0
GLEASON_SCORE	Spearman correlation test	N=2	higher score	N=2	lower score	N=0
PSA_RESULT_PREOP	Spearman correlation test	N=2	higher psa_result_preop	N=2	lower psa_result_preop	N=0
PSA_VALUE	Spearman correlation test	N=2	higher psa_value	N=2	lower psa_value	N=0
RACE	Kruskal-Wallis test	N=0

Clinical variable #1: 'AGE'

2 variables related to 'AGE'.

Table S1. Basic characteristics of clinical feature: 'AGE'


AGE	Mean (SD)	60.41 (7.1)
	Significant variables	N = 2
	pos. correlated	2
	neg. correlated	0

List of 2 variables associated with 'AGE'

Table S2. Get Full Table List of 2 variables significantly correlated to 'AGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
MUTATIONRATE_NONSYNONYMOUS	0.2782	1.033e-05	2.07e-05
MUTATIONRATE_SILENT	0.1997	0.001714	0.00171

Clinical variable #2: 'AGE'

No variable related to 'AGE'.

Table S3. Basic characteristics of clinical feature: 'AGE'


AGE	Mean (SD)	60.41 (7.1)
	Significant variables	N = 0

Clinical variable #3: 'PATHOLOGY.T.STAGE'

One variable related to 'PATHOLOGY.T.STAGE'.

Table S4. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'


PATHOLOGY.T.STAGE	Mean (SD)	2.57 (0.54)
		N
	2	111
	3	129
	4	5

	Significant variables	N = 1
	pos. correlated	1
	neg. correlated	0

List of one variable associated with 'PATHOLOGY.T.STAGE'

Table S5. Get Full Table List of one variable significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
MUTATIONRATE_NONSYNONYMOUS	0.208	0.001056	0.00211

Clinical variable #4: 'PATHOLOGY.N.STAGE'

No variable related to 'PATHOLOGY.N.STAGE'.

Table S6. Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'


PATHOLOGY.N.STAGE	Labels	N
	class0	183
	class1	22

	Significant variables	N = 0

Clinical variable #5: 'HISTOLOGICAL.TYPE'

No variable related to 'HISTOLOGICAL.TYPE'.

Table S7. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'


HISTOLOGICAL.TYPE	Labels	N
	PROSTATE ADENOCARCINOMA OTHER SUBTYPE	5
	PROSTATE ADENOCARCINOMA ACINAR TYPE	242

	Significant variables	N = 0

Clinical variable #6: 'COMPLETENESS.OF.RESECTION'

No variable related to 'COMPLETENESS.OF.RESECTION'.

Table S8. Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'


COMPLETENESS.OF.RESECTION	Labels	N
	R0	175
	R1	51
	R2	2
	RX	6

	Significant variables	N = 0

Clinical variable #7: 'NUMBER.OF.LYMPH.NODES'

No variable related to 'NUMBER.OF.LYMPH.NODES'.

Table S9. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'


NUMBER.OF.LYMPH.NODES	Mean (SD)	0.18 (0.65)
	Value	N
	0	181
	1	14
	2	4
	3	3
	6	1

	Significant variables	N = 0

Clinical variable #8: 'GLEASON_SCORE_COMBINED'

2 variables related to 'GLEASON_SCORE_COMBINED'.

Table S10. Basic characteristics of clinical feature: 'GLEASON_SCORE_COMBINED'


GLEASON_SCORE_COMBINED	Mean (SD)	7.32 (0.84)
	Significant variables	N = 2
	pos. correlated	2
	neg. correlated	0

List of 2 variables associated with 'GLEASON_SCORE_COMBINED'

Table S11. Get Full Table List of 2 variables significantly correlated to 'GLEASON_SCORE_COMBINED' by Spearman correlation test

	SpearmanCorr	corrP	Q
MUTATIONRATE_NONSYNONYMOUS	0.2112	0.0008388	0.00168
MUTATIONRATE_SILENT	0.1799	0.004566	0.00457

Clinical variable #9: 'GLEASON_SCORE_PRIMARY'

2 variables related to 'GLEASON_SCORE_PRIMARY'.

Table S12. Basic characteristics of clinical feature: 'GLEASON_SCORE_PRIMARY'


GLEASON_SCORE_PRIMARY	Mean (SD)	3.49 (0.58)
	Score	N
	2	1
	3	132
	4	105
	5	9

	Significant variables	N = 2
	pos. correlated	2
	neg. correlated	0

List of 2 variables associated with 'GLEASON_SCORE_PRIMARY'

Table S13. Get Full Table List of 2 variables significantly correlated to 'GLEASON_SCORE_PRIMARY' by Spearman correlation test

	SpearmanCorr	corrP	Q
MUTATIONRATE_NONSYNONYMOUS	0.263	2.84e-05	5.68e-05
MUTATIONRATE_SILENT	0.2225	0.0004248	0.000425

Clinical variable #10: 'GLEASON_SCORE_SECONDARY'

No variable related to 'GLEASON_SCORE_SECONDARY'.

Table S14. Basic characteristics of clinical feature: 'GLEASON_SCORE_SECONDARY'


GLEASON_SCORE_SECONDARY	Mean (SD)	3.83 (0.64)
	Score	N
	3	75
	4	140
	5	32

	Significant variables	N = 0

Clinical variable #11: 'GLEASON_SCORE'

2 variables related to 'GLEASON_SCORE'.

Table S15. Basic characteristics of clinical feature: 'GLEASON_SCORE'


GLEASON_SCORE	Mean (SD)	7.36 (0.86)
	Score	N
	6	19
	7	161
	8	28
	9	37
	10	2

	Significant variables	N = 2
	pos. correlated	2
	neg. correlated	0

List of 2 variables associated with 'GLEASON_SCORE'

Table S16. Get Full Table List of 2 variables significantly correlated to 'GLEASON_SCORE' by Spearman correlation test

	SpearmanCorr	corrP	Q
MUTATIONRATE_NONSYNONYMOUS	0.2022	0.001401	0.0028
MUTATIONRATE_SILENT	0.1947	0.002111	0.0028

Clinical variable #12: 'PSA_RESULT_PREOP'

2 variables related to 'PSA_RESULT_PREOP'.

Table S17. Basic characteristics of clinical feature: 'PSA_RESULT_PREOP'


PSA_RESULT_PREOP	Mean (SD)	10.29 (10)
	Significant variables	N = 2
	pos. correlated	2
	neg. correlated	0

List of 2 variables associated with 'PSA_RESULT_PREOP'

Table S18. Get Full Table List of 2 variables significantly correlated to 'PSA_RESULT_PREOP' by Spearman correlation test

	SpearmanCorr	corrP	Q
MUTATIONRATE_SILENT	0.1737	0.006403	0.0128
MUTATIONRATE_NONSYNONYMOUS	0.1427	0.0255	0.0255

Clinical variable #13: 'PSA_VALUE'

2 variables related to 'PSA_VALUE'.

Table S19. Basic characteristics of clinical feature: 'PSA_VALUE'


PSA_VALUE	Mean (SD)	1.16 (4)
	Significant variables	N = 2
	pos. correlated	2
	neg. correlated	0

List of 2 variables associated with 'PSA_VALUE'

Table S20. Get Full Table List of 2 variables significantly correlated to 'PSA_VALUE' by Spearman correlation test

	SpearmanCorr	corrP	Q
MUTATIONRATE_NONSYNONYMOUS	0.1988	0.003815	0.00763
MUTATIONRATE_SILENT	0.1396	0.04332	0.0433

Clinical variable #14: 'RACE'

No variable related to 'RACE'.

Table S21. Basic characteristics of clinical feature: 'RACE'


RACE	Labels	N
	ASIAN	2
	BLACK OR AFRICAN AMERICAN	7
	WHITE	147

	Significant variables	N = 0

Methods & Data

Input

Expresson data file = PRAD-TP.patients.counts_and_rates.txt
Clinical data file = PRAD-TP.merged_data.txt
Number of patients = 247
Number of variables = 2
Number of clinical features = 14

Correlation analysis

For continuous numerical clinical features, Spearman's rank correlation coefficients (Spearman 1904) and two-tailed P values were estimated using 'cor.test' function in R

Student's t-test analysis

For two-class clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the log2-expression levels between the two clinical classes using 't.test' function in R

ANOVA analysis

For multi-class clinical features (ordinal or nominal), one-way analysis of variance (Howell 2002) was applied to compare the log2-expression levels between different clinical classes using 'anova' 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] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)

[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)

[3] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)

[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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