Correlation between mRNA expression and clinical features

Colon Adenocarcinoma (Primary solid tumor)

23 September 2013 | analyses__2013_09_23

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 (2013): Correlation between mRNA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1N29V7J

Overview

Introduction

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

Summary

Testing the association between 17814 genes and 10 clinical features across 153 samples, statistically thresholded by Q value < 0.05, 6 clinical features related to at least one genes.

1 gene correlated to 'AGE'.

ANAPC1

2 genes correlated to 'NEOPLASM.DISEASESTAGE'.

KCNC2 , ZNF234

1 gene correlated to 'PATHOLOGY.M.STAGE'.

KCNC2

19 genes correlated to 'GENDER'.

DDX3Y , JARID1D , EIF1AY , RPS4Y1 , CYORF15A , ...

80 genes correlated to 'HISTOLOGICAL.TYPE'.

PPP1R9A , AGR2 , C10ORF82 , C20ORF24 , DYNLRB1 , ...

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

CRH , CT45-6 , COX7B2 , CTAG2 , RP13-36C9.6 , ...

No genes correlated to 'Time to Death', 'PATHOLOGY.T.STAGE', 'PATHOLOGY.N.STAGE', 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
Time to Death	Cox regression test	N=0
AGE	Spearman correlation test	N=1	older	N=0	younger	N=1
NEOPLASM DISEASESTAGE	ANOVA test	N=2
PATHOLOGY T STAGE	Spearman correlation test	N=0
PATHOLOGY N STAGE	Spearman correlation test	N=0
PATHOLOGY M STAGE	ANOVA test	N=1
GENDER	t test	N=19	male	N=13	female	N=6
HISTOLOGICAL TYPE	t test	N=80	colon mucinous adenocarcinoma	N=40	colon adenocarcinoma	N=40
COMPLETENESS OF RESECTION	ANOVA test	N=49
NUMBER OF LYMPH NODES	Spearman correlation test	N=0

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)	0.9-52 (median=4)
	censored	N = 62
	death	N = 13

	Significant markers	N = 0

Clinical variable #2: 'AGE'

One gene related to 'AGE'.

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


AGE	Mean (SD)	70.77 (12)
	Significant markers	N = 1
	pos. correlated	0
	neg. correlated	1

List of one gene significantly correlated to 'AGE' by Spearman correlation test

Table S3. Get Full Table List of one gene significantly correlated to 'AGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
ANAPC1	-0.3901	6.195e-07	0.011

Figure S1. Get High-res Image As an example, this figure shows the association of ANAPC1 to 'AGE'. P value = 6.19e-07 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

2 genes related to 'NEOPLASM.DISEASESTAGE'.

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


NEOPLASM.DISEASESTAGE	Labels	N
	STAGE I	29
	STAGE II	12
	STAGE IIA	45
	STAGE IIB	5
	STAGE III	8
	STAGE IIIA	3
	STAGE IIIB	12
	STAGE IIIC	16
	STAGE IV	21
	STAGE IVA	1

	Significant markers	N = 2

List of 2 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S5. Get Full Table List of 2 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

	ANOVA_P	Q
KCNC2	1.227e-10	2.19e-06
ZNF234	1.69e-06	0.0301

Figure S2. Get High-res Image As an example, this figure shows the association of KCNC2 to 'NEOPLASM.DISEASESTAGE'. P value = 1.23e-10 with ANOVA analysis.

Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

Table S6. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'


PATHOLOGY.T.STAGE	Mean (SD)	2.84 (0.62)
		N
	1	4
	2	31
	3	103
	4	15

	Significant markers	N = 0

Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

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


PATHOLOGY.N.STAGE	Mean (SD)	0.59 (0.81)
		N
	0	94
	1	28
	2	31

	Significant markers	N = 0

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

One gene related to 'PATHOLOGY.M.STAGE'.

Table S8. Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'


PATHOLOGY.M.STAGE	Labels	N
	M0	129
	M1	21
	M1A	1

	Significant markers	N = 1

List of one gene differentially expressed by 'PATHOLOGY.M.STAGE'

Table S9. Get Full Table List of one gene differentially expressed by 'PATHOLOGY.M.STAGE'

	ANOVA_P	Q
KCNC2	4.483e-14	7.99e-10

Figure S3. Get High-res Image As an example, this figure shows the association of KCNC2 to 'PATHOLOGY.M.STAGE'. P value = 4.48e-14 with ANOVA analysis.

Clinical variable #7: 'GENDER'

19 genes related to 'GENDER'.

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


GENDER	Labels	N
	FEMALE	75
	MALE	78

	Significant markers	N = 19
	Higher in MALE	13
	Higher in FEMALE	6

List of top 10 genes differentially expressed by 'GENDER'

Table S11. Get Full Table List of top 10 genes differentially expressed by 'GENDER'

	T(pos if higher in 'MALE')	ttestP	Q	AUC
DDX3Y	22.4	1.044e-49	1.86e-45	0.9745
JARID1D	20.6	1.058e-45	1.89e-41	0.9779
EIF1AY	20.54	1.789e-45	3.19e-41	0.9646
RPS4Y1	19.07	6.998e-42	1.25e-37	0.9491
CYORF15A	18.54	2.002e-40	3.57e-36	0.9554
RPS4Y2	18.23	1.391e-39	2.48e-35	0.9622
UTY	17.98	2.603e-38	4.63e-34	0.9586
CYORF15B	15.65	6.536e-33	1.16e-28	0.9462
ZFY	15.45	6.937e-33	1.24e-28	0.9489
USP9Y	10.76	2.866e-20	5.1e-16	0.8926

Figure S4. Get High-res Image As an example, this figure shows the association of DDX3Y to 'GENDER'. P value = 1.04e-49 with T-test analysis.

Clinical variable #8: 'HISTOLOGICAL.TYPE'

80 genes related to 'HISTOLOGICAL.TYPE'.

Table S12. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'


HISTOLOGICAL.TYPE	Labels	N
	COLON ADENOCARCINOMA	129
	COLON MUCINOUS ADENOCARCINOMA	22

	Significant markers	N = 80
	Higher in COLON MUCINOUS ADENOCARCINOMA	40
	Higher in COLON ADENOCARCINOMA	40

List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S13. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

	T(pos if higher in 'COLON MUCINOUS ADENOCARCINOMA')	ttestP	Q	AUC
PPP1R9A	7.13	1.007e-10	1.79e-06	0.7343
AGR2	7.95	5.429e-10	9.67e-06	0.8696
C10ORF82	-7.34	2.494e-09	4.44e-05	0.8214
C20ORF24	-7.24	5.567e-09	9.91e-05	0.8298
DYNLRB1	-7.12	5.896e-09	0.000105	0.8238
SLC39A9	7.12	6.485e-09	0.000115	0.8319
RDHE2	7.06	1.208e-08	0.000215	0.8118
C9ORF125	6.35	1.476e-08	0.000263	0.7838
SPDEF	7.31	2.606e-08	0.000464	0.8626
KCTD12	6.64	3.84e-08	0.000684	0.8164

Figure S5. Get High-res Image As an example, this figure shows the association of PPP1R9A to 'HISTOLOGICAL.TYPE'. P value = 1.01e-10 with T-test analysis.

Clinical variable #9: 'COMPLETENESS.OF.RESECTION'

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

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


COMPLETENESS.OF.RESECTION	Labels	N
	R0	128
	R1	1
	R2	19

	Significant markers	N = 49

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

Table S15. Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

	ANOVA_P	Q
CRH	2.852e-26	5.08e-22
CT45-6	3.18e-18	5.66e-14
COX7B2	3.228e-18	5.75e-14
CTAG2	6.913e-17	1.23e-12
RP13-36C9.6	1.352e-15	2.41e-11
PAGE4	8.012e-15	1.43e-10
HOXC13	2.348e-14	4.18e-10
LGALS14	1.18e-13	2.1e-09
RARA	2.993e-13	5.33e-09
HOXC12	3.207e-13	5.71e-09

Figure S6. Get High-res Image As an example, this figure shows the association of CRH to 'COMPLETENESS.OF.RESECTION'. P value = 2.85e-26 with ANOVA analysis.

Clinical variable #10: 'NUMBER.OF.LYMPH.NODES'

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

Table S16. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'


NUMBER.OF.LYMPH.NODES	Mean (SD)	2.14 (4.5)
	Significant markers	N = 0

Methods & Data

Input

Expresson data file = COAD-TP.medianexp.txt
Clinical data file = COAD-TP.clin.merged.picked.txt
Number of patients = 153
Number of genes = 17814
Number of clinical features = 10

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)

Made with Nozzle