Correlation between mutation rate and clinical features

Lung Adenocarcinoma (Primary solid tumor)

17 October 2014 | analyses__2014_10_17

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/C1SQ8Z93

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 172 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 1 clinical feature related to at least one variables.

2 variables correlated to 'NUMBERPACKYEARSSMOKED'.

MUTATIONRATE_NONSYNONYMOUS , MUTATIONRATE_SILENT

No variables correlated to 'Time to Death', 'AGE', 'AGE_mutation.rate', 'NEOPLASM.DISEASESTAGE', 'PATHOLOGY.T.STAGE', 'PATHOLOGY.N.STAGE', 'PATHOLOGY.M.STAGE', 'GENDER', 'KARNOFSKY.PERFORMANCE.SCORE', 'HISTOLOGICAL.TYPE', 'RADIATIONS.RADIATION.REGIMENINDICATION', 'COMPLETENESS.OF.RESECTION', 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
Time to Death	Cox regression test	N=0
AGE	Spearman correlation test	N=0
AGE	Linear Regression Analysis	N=0
NEOPLASM DISEASESTAGE	Kruskal-Wallis test	N=0
PATHOLOGY T STAGE	Spearman correlation test	N=0
PATHOLOGY N STAGE	Spearman correlation test	N=0
PATHOLOGY M STAGE	Kruskal-Wallis test	N=0
GENDER	Wilcoxon test	N=0
KARNOFSKY PERFORMANCE SCORE	Spearman correlation test	N=0
HISTOLOGICAL TYPE	Kruskal-Wallis test	N=0
RADIATIONS RADIATION REGIMENINDICATION	Wilcoxon test	N=0
NUMBERPACKYEARSSMOKED	Spearman correlation test	N=2	higher numberpackyearssmoked	N=2	lower numberpackyearssmoked	N=0
COMPLETENESS OF RESECTION	Kruskal-Wallis test	N=0
RACE	Kruskal-Wallis test	N=0

Clinical variable #1: 'Time to Death'

No variable related to 'Time to Death'.

Table S1. Basic characteristics of clinical feature: 'Time to Death'


Time to Death	Duration (Years)	2-2370 (median=735.5)
	censored	N = 100
	death	N = 38

	Significant variables	N = 0

Clinical variable #2: 'AGE'

No variable related to 'AGE'.

Table S2. Basic characteristics of clinical feature: 'AGE'


AGE	Mean (SD)	65.43 (10)
	Significant variables	N = 0

Clinical variable #3: 'AGE'

No variable related to 'AGE'.

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


AGE	Mean (SD)	65.43 (10)
	Significant variables	N = 0

Clinical variable #4: 'NEOPLASM.DISEASESTAGE'

No variable related to 'NEOPLASM.DISEASESTAGE'.

Table S4. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'


NEOPLASM.DISEASESTAGE	Labels	N
	STAGE IA	37
	STAGE IB	53
	STAGE IIA	11
	STAGE IIB	23
	STAGE IIIA	33
	STAGE IIIB	6
	STAGE IV	9

	Significant variables	N = 0

Clinical variable #5: 'PATHOLOGY.T.STAGE'

No variable related to 'PATHOLOGY.T.STAGE'.

Table S5. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'


PATHOLOGY.T.STAGE	Mean (SD)	1.94 (0.71)
		N
	1	41
	2	109
	3	14
	4	8

	Significant variables	N = 0

Clinical variable #6: 'PATHOLOGY.N.STAGE'

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

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


PATHOLOGY.N.STAGE	Mean (SD)	0.65 (0.82)
		N
	0	95
	1	37
	2	34
	3	1

	Significant variables	N = 0

Clinical variable #7: 'PATHOLOGY.M.STAGE'

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

Table S7. Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'


PATHOLOGY.M.STAGE	Labels	N
	M0	143
	M1	9
	MX	18

	Significant variables	N = 0

Clinical variable #8: 'GENDER'

No variable related to 'GENDER'.

Table S8. Basic characteristics of clinical feature: 'GENDER'


GENDER	Labels	N
	FEMALE	93
	MALE	79

	Significant variables	N = 0

Clinical variable #9: 'KARNOFSKY.PERFORMANCE.SCORE'

No variable related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S9. Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'


KARNOFSKY.PERFORMANCE.SCORE	Mean (SD)	65 (41)
	Significant variables	N = 0

Clinical variable #10: 'HISTOLOGICAL.TYPE'

No variable related to 'HISTOLOGICAL.TYPE'.

Table S10. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'


HISTOLOGICAL.TYPE	Labels	N
	LUNG ACINAR ADENOCARCINOMA	2
	LUNG ADENOCARCINOMA MIXED SUBTYPE	39
	LUNG ADENOCARCINOMA- NOT OTHERWISE SPECIFIED (NOS)	115
	LUNG BRONCHIOLOALVEOLAR CARCINOMA MUCINOUS	1
	LUNG BRONCHIOLOALVEOLAR CARCINOMA NONMUCINOUS	2
	LUNG CLEAR CELL ADENOCARCINOMA	2
	LUNG MICROPAPILLARY ADENOCARCINOMA	2
	LUNG MUCINOUS ADENOCARCINOMA	2
	LUNG PAPILLARY ADENOCARCINOMA	4
	LUNG SOLID PATTERN PREDOMINANT ADENOCARCINOMA	1
	MUCINOUS (COLLOID) CARCINOMA	2

	Significant variables	N = 0

Clinical variable #11: 'RADIATIONS.RADIATION.REGIMENINDICATION'

No variable related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S11. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'


RADIATIONS.RADIATION.REGIMENINDICATION	Labels	N
	NO	15
	YES	157

	Significant variables	N = 0

Clinical variable #12: 'NUMBERPACKYEARSSMOKED'

2 variables related to 'NUMBERPACKYEARSSMOKED'.

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


NUMBERPACKYEARSSMOKED	Mean (SD)	40.7 (25)
	Significant variables	N = 2
	pos. correlated	2
	neg. correlated	0

List of 2 variables associated with 'NUMBERPACKYEARSSMOKED'

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

	SpearmanCorr	corrP	Q
MUTATIONRATE_NONSYNONYMOUS	0.2184	0.02071	0.0414
MUTATIONRATE_SILENT	0.1878	0.04738	0.0474

Clinical variable #13: 'COMPLETENESS.OF.RESECTION'

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

Table S14. Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'


COMPLETENESS.OF.RESECTION	Labels	N
	R0	115
	R1	6
	R2	4
	RX	9

	Significant variables	N = 0

Clinical variable #14: 'RACE'

No variable related to 'RACE'.

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


RACE	Labels	N
	AMERICAN INDIAN OR ALASKA NATIVE	1
	ASIAN	3
	BLACK OR AFRICAN AMERICAN	9
	WHITE	113

	Significant variables	N = 0

Methods & Data

Input

Expresson data file = LUAD-TP.patients.counts_and_rates.txt
Clinical data file = LUAD-TP.merged_data.txt
Number of patients = 172
Number of variables = 2
Number of clinical features = 14

Survival analysis

For survival clinical features, Wald's test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values using the 'coxph' function in R. Kaplan-Meier survival curves were plot using the four quartile subgroups of patients based on expression levels

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

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

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

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] Andersen and Gill, Cox's regression model for counting processes, a large sample study, Annals of Statistics 10(4):1100-1120 (1982)

[2] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)

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

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

[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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