Correlation between gene methylation status and clinical features

Prostate Adenocarcinoma (Primary solid tumor)

21 April 2013 | analyses__2013_04_21

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Prostate Adenocarcinoma (Primary solid tumor cohort) - 21 April 2013: Correlation between gene methylation status and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C18W3B9T

Overview

Introduction

This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.

Summary

Testing the association between 17313 genes and 4 clinical features across 150 samples, statistically thresholded by Q value < 0.05, 2 clinical features related to at least one genes.

89 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

NAA20 , ZNF280D , BCAS2 , AASDHPPT , VWDE , ...

4 genes correlated to 'COMPLETENESS.OF.RESECTION'.

WHAMM , CD36 , TGM4 , ZNF219

No genes correlated to 'AGE', and 'NUMBER.OF.LYMPH.NODES'.

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 genes that are significantly associated with each clinical feature at Q value < 0.05.

Clinical feature	Statistical test	Significant genes	Associated with		Associated with
AGE	Spearman correlation test	N=0
RADIATIONS RADIATION REGIMENINDICATION	t test	N=89	yes	N=56	no	N=33
COMPLETENESS OF RESECTION	ANOVA test	N=4
NUMBER OF LYMPH NODES	Spearman correlation test	N=0

Clinical variable #1: 'AGE'

No gene related to 'AGE'.

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


AGE	Mean (SD)	60.3 (6.8)
	Significant markers	N = 0

Clinical variable #2: 'RADIATIONS.RADIATION.REGIMENINDICATION'

89 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S2. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'


RADIATIONS.RADIATION.REGIMENINDICATION	Labels	N
	NO	5
	YES	145

	Significant markers	N = 89
	Higher in YES	56
	Higher in NO	33

List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S3. Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

	T(pos if higher in 'YES')	ttestP	Q	AUC
NAA20	11.13	3.896e-17	6.74e-13	0.8676
ZNF280D	10.9	1.563e-16	2.71e-12	0.8207
BCAS2	8.86	7.037e-15	1.22e-10	0.7683
AASDHPPT	9.06	7.451e-15	1.29e-10	0.8761
VWDE	8.42	3.465e-14	6e-10	0.7793
ZKSCAN4	11.29	4.078e-13	7.06e-09	0.8814
CLEC4C	-8.18	6.031e-13	1.04e-08	0.7379
KCNA4	-8.73	6.356e-13	1.1e-08	0.7545
PIK3CA	8.44	7.373e-13	1.28e-08	0.8292
VCAN	-9.32	8.649e-13	1.5e-08	0.7655

Figure S1. Get High-res Image As an example, this figure shows the association of NAA20 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 3.9e-17 with T-test analysis.

Clinical variable #3: 'COMPLETENESS.OF.RESECTION'

4 genes related to 'COMPLETENESS.OF.RESECTION'.

Table S4. Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'


COMPLETENESS.OF.RESECTION	Labels	N
	R0	114
	R1	29
	RX	2

	Significant markers	N = 4

List of 4 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S5. Get Full Table List of 4 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

	ANOVA_P	Q
WHAMM	3.612e-20	6.25e-16
CD36	3.046e-08	0.000527
TGM4	1.666e-07	0.00288
ZNF219	1.139e-06	0.0197

Figure S2. Get High-res Image As an example, this figure shows the association of WHAMM to 'COMPLETENESS.OF.RESECTION'. P value = 3.61e-20 with ANOVA analysis.

Clinical variable #4: 'NUMBER.OF.LYMPH.NODES'

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

Table S6. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'


NUMBER.OF.LYMPH.NODES	Mean (SD)	0.21 (0.75)
	Significant markers	N = 0

Methods & Data

Input

Expresson data file = PRAD-TP.meth.for_correlation.filtered_data.txt
Clinical data file = PRAD-TP.clin.merged.picked.txt
Number of patients = 150
Number of genes = 17313
Number of clinical features = 4

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

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] 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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