Correlation between mRNA expression and clinical features

Ovarian Serous Cystadenocarcinoma (Primary solid tumor)

17 October 2014 | analyses__2014_10_17

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 mRNA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C16972GS

Overview

Introduction

This pipeline uses various statistical tests to identify mRNAs whose log2 expression levels correlated to selected clinical features.

Summary

Testing the association between 18632 genes and 8 clinical features across 562 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 3 clinical features related to at least one genes.

5 genes correlated to 'Time to Death'.

ZFHX4 , PPM2C , TLL1 , LUZP1 , EXOC6B

329 genes correlated to 'AGE'.

STS , GREB1 , DEPDC6 , GNPNAT1 , SLCO1A2 , ...

2 genes correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

WDR60 , NDUFA13

No genes correlated to 'PRIMARY.SITE.OF.DISEASE', 'RADIATIONS.RADIATION.REGIMENINDICATION', 'COMPLETENESS.OF.RESECTION', 'RACE', and 'ETHNICITY'.

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 P value < 0.05 and Q value < 0.3.

Clinical feature	Statistical test	Significant genes	Associated with		Associated with
Time to Death	Cox regression test	N=5	shorter survival	N=5	longer survival	N=0
AGE	Spearman correlation test	N=329	older	N=129	younger	N=200
PRIMARY SITE OF DISEASE	Kruskal-Wallis test	N=0
KARNOFSKY PERFORMANCE SCORE	Spearman correlation test	N=2	higher score	N=1	lower score	N=1
RADIATIONS RADIATION REGIMENINDICATION	Wilcoxon test	N=0
COMPLETENESS OF RESECTION	Kruskal-Wallis test	N=0
RACE	Kruskal-Wallis test	N=0
ETHNICITY	Wilcoxon test	N=0

Clinical variable #1: 'Time to Death'

5 genes related to 'Time to Death'.

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


Time to Death	Duration (Months)	0.3-180.2 (median=28.6)
	censored	N = 264
	death	N = 293

	Significant markers	N = 5
	associated with shorter survival	5
	associated with longer survival	0

List of 5 genes differentially expressed by 'Time to Death'

Table S2. Get Full Table List of 5 genes significantly associated with 'Time to Death' by Cox regression test

	HazardRatio	Wald_P	Q	C_index
ZFHX4	1.63	2.256e-06	0.042	0.575
PPM2C	1.75	5.43e-06	0.1	0.551
TLL1	1.51	9.396e-06	0.18	0.568
LUZP1	2.1	1.319e-05	0.25	0.579
EXOC6B	1.76	1.478e-05	0.28	0.57

Clinical variable #2: 'AGE'

329 genes related to 'AGE'.

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


AGE	Mean (SD)	59.72 (12)
	Significant markers	N = 329
	pos. correlated	129
	neg. correlated	200

List of top 10 genes differentially expressed by 'AGE'

Table S4. Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
STS	-0.307	1.713e-13	3.19e-09
GREB1	-0.3024	4.058e-13	7.56e-09
DEPDC6	-0.301	5.286e-13	9.85e-09
GNPNAT1	-0.2963	1.261e-12	2.35e-08
SLCO1A2	0.2853	8.849e-12	1.65e-07
EIF4E3	-0.2847	9.779e-12	1.82e-07
NPAL2	-0.2761	4.258e-11	7.93e-07
BRCC3	-0.275	5.105e-11	9.51e-07
NLK	0.2749	5.176e-11	9.64e-07
APPL2	0.2747	5.406e-11	1.01e-06

Clinical variable #3: 'PRIMARY.SITE.OF.DISEASE'

No gene related to 'PRIMARY.SITE.OF.DISEASE'.

Table S5. Basic characteristics of clinical feature: 'PRIMARY.SITE.OF.DISEASE'


PRIMARY.SITE.OF.DISEASE	Labels	N
	OMENTUM	2
	OVARY	558
	PERITONEUM OVARY	2

	Significant markers	N = 0

Clinical variable #4: 'KARNOFSKY.PERFORMANCE.SCORE'

2 genes related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S6. Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'


KARNOFSKY.PERFORMANCE.SCORE	Mean (SD)	75.64 (13)
	Score	N
	40	2
	60	20
	80	49
	100	7

	Significant markers	N = 2
	pos. correlated	1
	neg. correlated	1

List of 2 genes differentially expressed by 'KARNOFSKY.PERFORMANCE.SCORE'

Table S7. Get Full Table List of 2 genes significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

	SpearmanCorr	corrP	Q
WDR60	0.504	2.551e-06	0.0475
NDUFA13	-0.4722	1.276e-05	0.238

Clinical variable #5: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S8. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'


RADIATIONS.RADIATION.REGIMENINDICATION	Labels	N
	NO	3
	YES	559

	Significant markers	N = 0

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

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

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


COMPLETENESS.OF.RESECTION	Labels	N
	R0	14
	R1	27
	R2	1

	Significant markers	N = 0

Clinical variable #7: 'RACE'

No gene related to 'RACE'.

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


RACE	Labels	N
	AMERICAN INDIAN OR ALASKA NATIVE	2
	ASIAN	19
	BLACK OR AFRICAN AMERICAN	24
	NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER	1
	WHITE	485

	Significant markers	N = 0

Clinical variable #8: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S11. Basic characteristics of clinical feature: 'ETHNICITY'


ETHNICITY	Labels	N
	HISPANIC OR LATINO	11
	NOT HISPANIC OR LATINO	328

	Significant markers	N = 0

Methods & Data

Input

Expresson data file = OV-TP.medianexp.txt
Clinical data file = OV-TP.merged_data.txt
Number of patients = 562
Number of genes = 18632
Number of clinical features = 8

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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