Correlation between gene methylation status and clinical features

Liver Hepatocellular Carcinoma (Primary solid tumor)

23 May 2013 | analyses__2013_05_23

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between gene methylation status and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1N29V0D

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 19728 genes and 7 clinical features across 69 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

2 genes correlated to 'GENDER'.

ALG11__1 , UTP14C

14 genes correlated to 'DISTANT.METASTASIS'.

SEPSECS , C5ORF42 , BIVM , KDELC1 , GOLGA7 , ...

50 genes correlated to 'LYMPH.NODE.METASTASIS'.

LDHAL6B , MYO1E , MORC1 , HECA , SYTL3 , ...

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

SEPSECS , C5ORF42 , BIVM , KDELC1 , GOLGA7 , ...

44 genes correlated to 'NEOPLASM.DISEASESTAGE'.

SEPSECS , LDHAL6B , MYO1E , MORC1 , HECA , ...

No genes correlated to 'Time to Death', and 'AGE'.

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
Time to Death	Cox regression test	N=0
AGE	Spearman correlation test	N=0
GENDER	t test	N=2	male	N=2	female	N=0
DISTANT METASTASIS	ANOVA test	N=14
LYMPH NODE METASTASIS	ANOVA test	N=50
COMPLETENESS OF RESECTION	ANOVA test	N=12
NEOPLASM DISEASESTAGE	ANOVA test	N=44

Clinical variable #1: 'Time to Death'

No gene related to 'Time to Death'.

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


Time to Death	Duration (Months)	0.1-90.7 (median=11.5)
	censored	N = 39
	death	N = 23

	Significant markers	N = 0

Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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


AGE	Mean (SD)	59.27 (15)
	Significant markers	N = 0

Clinical variable #3: 'GENDER'

2 genes related to 'GENDER'.

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


GENDER	Labels	N
	FEMALE	24
	MALE	45

	Significant markers	N = 2
	Higher in MALE	2
	Higher in FEMALE	0

List of 2 genes differentially expressed by 'GENDER'

Table S4. Get Full Table List of 2 genes differentially expressed by 'GENDER'

	T(pos if higher in 'MALE')	ttestP	Q	AUC
ALG11__1	9.57	3.879e-10	7.65e-06	0.9556
UTP14C	9.57	3.879e-10	7.65e-06	0.9556

Figure S1. Get High-res Image As an example, this figure shows the association of ALG11__1 to 'GENDER'. P value = 3.88e-10 with T-test analysis.

Clinical variable #4: 'DISTANT.METASTASIS'

14 genes related to 'DISTANT.METASTASIS'.

Table S5. Basic characteristics of clinical feature: 'DISTANT.METASTASIS'


DISTANT.METASTASIS	Labels	N
	M0	48
	M1	1
	MX	20

	Significant markers	N = 14

List of top 10 genes differentially expressed by 'DISTANT.METASTASIS'

Table S6. Get Full Table List of top 10 genes differentially expressed by 'DISTANT.METASTASIS'

	ANOVA_P	Q
SEPSECS	1.602e-49	3.16e-45
C5ORF42	2.678e-16	5.28e-12
BIVM	7.362e-14	1.45e-09
KDELC1	7.362e-14	1.45e-09
GOLGA7	7.105e-12	1.4e-07
C4ORF12	1.443e-08	0.000285
WDFY3	1.443e-08	0.000285
HDLBP	5.299e-08	0.00105
SEPT2	5.299e-08	0.00105
MGMT	1.605e-07	0.00316

Figure S2. Get High-res Image As an example, this figure shows the association of SEPSECS to 'DISTANT.METASTASIS'. P value = 1.6e-49 with ANOVA analysis.

Clinical variable #5: 'LYMPH.NODE.METASTASIS'

50 genes related to 'LYMPH.NODE.METASTASIS'.

Table S7. Basic characteristics of clinical feature: 'LYMPH.NODE.METASTASIS'


LYMPH.NODE.METASTASIS	Labels	N
	N0	48
	N1	1
	NX	19

	Significant markers	N = 50

List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

Table S8. Get Full Table List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

	ANOVA_P	Q
LDHAL6B	8.555e-40	1.69e-35
MYO1E	8.555e-40	1.69e-35
MORC1	3.054e-35	6.02e-31
HECA	5.097e-31	1.01e-26
SYTL3	7.418e-29	1.46e-24
RAB20	9.31e-29	1.84e-24
RFX2	2.07e-24	4.08e-20
MAEL	1.99e-22	3.92e-18
ASB14	2.407e-18	4.75e-14
DHX58	1.492e-17	2.94e-13

Figure S3. Get High-res Image As an example, this figure shows the association of LDHAL6B to 'LYMPH.NODE.METASTASIS'. P value = 8.56e-40 with ANOVA analysis.

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

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

Table S9. Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'


COMPLETENESS.OF.RESECTION	Labels	N
	R0	49
	R1	5
	R2	1
	RX	9

	Significant markers	N = 12

List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S10. Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

	ANOVA_P	Q
SEPSECS	4.057e-45	8e-41
C5ORF42	6.783e-16	1.34e-11
BIVM	3.979e-12	7.85e-08
KDELC1	3.979e-12	7.85e-08
GOLGA7	1.966e-10	3.88e-06
IREB2	6.378e-09	0.000126
C4ORF12	3.533e-08	0.000697
WDFY3	3.533e-08	0.000697
HDLBP	4.82e-07	0.0095
SEPT2	4.82e-07	0.0095

Figure S4. Get High-res Image As an example, this figure shows the association of SEPSECS to 'COMPLETENESS.OF.RESECTION'. P value = 4.06e-45 with ANOVA analysis.

Clinical variable #7: 'NEOPLASM.DISEASESTAGE'

44 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S11. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'


NEOPLASM.DISEASESTAGE	Labels	N
	STAGE I	28
	STAGE II	12
	STAGE IIIA	15
	STAGE IIIB	4
	STAGE IIIC	1
	STAGE IVB	1

	Significant markers	N = 44

List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S12. Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

	ANOVA_P	Q
SEPSECS	1.289e-40	2.54e-36
LDHAL6B	7.607e-32	1.5e-27
MYO1E	7.607e-32	1.5e-27
MORC1	5.066e-29	9.99e-25
HECA	1.373e-25	2.71e-21
SYTL3	5.214e-24	1.03e-19
RAB20	1.44e-23	2.84e-19
MAEL	1.528e-21	3.01e-17
RFX2	1.575e-19	3.11e-15
DHX58	1.643e-18	3.24e-14

Figure S5. Get High-res Image As an example, this figure shows the association of SEPSECS to 'NEOPLASM.DISEASESTAGE'. P value = 1.29e-40 with ANOVA analysis.

Methods & Data

Input

Expresson data file = LIHC-TP.meth.by_min_expr_corr.data.txt
Clinical data file = LIHC-TP.clin.merged.picked.txt
Number of patients = 69
Number of genes = 19728
Number of clinical features = 7

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

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

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

[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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