Correlation between mRNA expression and clinical features

Colorectal Adenocarcinoma (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/C16W98Z5

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 17814 genes and 11 clinical features across 222 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 8 clinical features related to at least one genes.

1 gene correlated to 'AGE'.

ANAPC1

71 genes correlated to 'PRIMARY.SITE.OF.DISEASE'.

GPX2 , PRAC , CEACAM5 , CFTR , LGALS4 , ...

2 genes correlated to 'PATHOLOGY.T.STAGE'.

RBP7 , EDG3

2 genes correlated to 'PATHOLOGY.N.STAGE'.

LUZP2 , NFKBIZ

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

ZNF273

9 genes correlated to 'GENDER'.

JARID1D , CYORF15A , CYORF15B , UTX , HDHD1A , ...

336 genes correlated to 'HISTOLOGICAL.TYPE'.

AGR2 , PRAC , GPX2 , GFI1 , SRBD1 , ...

2 genes correlated to 'NUMBER.OF.LYMPH.NODES'.

LUZP2 , NFKBIZ

No genes correlated to 'Time to Death', 'NEOPLASM.DISEASESTAGE', and 'COMPLETENESS.OF.RESECTION'.

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=0
AGE	Spearman correlation test	N=1	older	N=0	younger	N=1
PRIMARY SITE OF DISEASE	Wilcoxon test	N=71	rectum	N=71	colon	N=0
NEOPLASM DISEASESTAGE	Kruskal-Wallis test	N=0
PATHOLOGY T STAGE	Spearman correlation test	N=2	higher stage	N=2	lower stage	N=0
PATHOLOGY N STAGE	Spearman correlation test	N=2	higher stage	N=1	lower stage	N=1
PATHOLOGY M STAGE	Kruskal-Wallis test	N=1
GENDER	Wilcoxon test	N=9	male	N=9	female	N=0
HISTOLOGICAL TYPE	Kruskal-Wallis test	N=336
COMPLETENESS OF RESECTION	Kruskal-Wallis test	N=0
NUMBER OF LYMPH NODES	Spearman correlation test	N=2	higher number.of.lymph.nodes	N=1	lower number.of.lymph.nodes	N=1

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)	0.9-54 (median=21)
	censored	N = 167
	death	N = 36

	Significant markers	N = 0

Clinical variable #2: 'AGE'

One gene related to 'AGE'.

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


AGE	Mean (SD)	69.49 (11)
	Significant markers	N = 1
	pos. correlated	0
	neg. correlated	1

List of one gene differentially expressed by 'AGE'

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

	SpearmanCorr	corrP	Q
ANAPC1	-0.3043	3.858e-06	0.0687

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

71 genes related to 'PRIMARY.SITE.OF.DISEASE'.

Table S4. Basic characteristics of clinical feature: 'PRIMARY.SITE.OF.DISEASE'


PRIMARY.SITE.OF.DISEASE	Labels	N
	COLON	152
	RECTUM	68

	Significant markers	N = 71
	Higher in RECTUM	71
	Higher in COLON	0

List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

Table S5. Get Full Table List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

	W(pos if higher in 'RECTUM')	wilcoxontestP	Q	AUC
GPX2	8100.5	1.815e-11	3.23e-07	0.7837
PRAC	8037.5	4.839e-11	8.62e-07	0.7776
CEACAM5	7972	1.313e-10	2.34e-06	0.7713
CFTR	7873	5.691e-10	1.01e-05	0.7617
LGALS4	7807	1.471e-09	2.62e-05	0.7553
C10ORF99	7701	6.454e-09	0.000115	0.7451
HOXB13	7699	6.633e-09	0.000118	0.7449
FAM3D	7695.5	6.958e-09	0.000124	0.7445
HSP90B3P	2693	1.415e-08	0.000252	0.7395
PDZK1IP1	7641	1.453e-08	0.000259	0.7393

Clinical variable #4: 'NEOPLASM.DISEASESTAGE'

No gene related to 'NEOPLASM.DISEASESTAGE'.

Table S6. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'


NEOPLASM.DISEASESTAGE	Labels	N
	STAGE I	47
	STAGE II	15
	STAGE IIA	65
	STAGE IIB	5
	STAGE III	10
	STAGE IIIA	3
	STAGE IIIB	22
	STAGE IIIC	20
	STAGE IV	33
	STAGE IVA	1

	Significant markers	N = 0

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

2 genes related to 'PATHOLOGY.T.STAGE'.

Table S7. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'


PATHOLOGY.T.STAGE	Mean (SD)	2.8 (0.64)
		N
	1	9
	2	46
	3	148
	4	19

	Significant markers	N = 2
	pos. correlated	2
	neg. correlated	0

List of 2 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S8. Get Full Table List of 2 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
RBP7	0.305	3.667e-06	0.0653
EDG3	0.2907	1.072e-05	0.191

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

2 genes related to 'PATHOLOGY.N.STAGE'.

Table S9. Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'


PATHOLOGY.N.STAGE	Mean (SD)	0.58 (0.8)
		N
	0	136
	1	43
	2	43

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

List of 2 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S10. Get Full Table List of 2 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
LUZP2	0.3103	2.434e-06	0.0434
NFKBIZ	-0.289	1.212e-05	0.216

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

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

Table S11. Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'


PATHOLOGY.M.STAGE	Labels	N
	M0	186
	M1	33
	M1A	1

	Significant markers	N = 1

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

Table S12. Get Full Table List of one gene differentially expressed by 'PATHOLOGY.M.STAGE'

	ANOVA_P	Q
ZNF273	1.237e-05	0.22

Clinical variable #8: 'GENDER'

9 genes related to 'GENDER'.

Table S13. Basic characteristics of clinical feature: 'GENDER'


GENDER	Labels	N
	FEMALE	106
	MALE	116

	Significant markers	N = 9
	Higher in MALE	9
	Higher in FEMALE	0

List of 9 genes differentially expressed by 'GENDER'

Table S14. Get Full Table List of 9 genes differentially expressed by 'GENDER'. 26 significant gene(s) located in sex chromosomes is(are) filtered out.

	W(pos if higher in 'MALE')	wilcoxontestP	Q	AUC
JARID1D	11915	1.649e-33	2.94e-29	0.969
CYORF15A	11715	2.434e-31	4.33e-27	0.9527
CYORF15B	11471.5	8.419e-29	1.5e-24	0.9329
UTX	3089.5	1.582e-10	2.82e-06	0.7487
HDHD1A	3231.5	1.059e-09	1.89e-05	0.7372
JARID1C	3543.5	5.108e-08	0.000909	0.7118
ZRSR1	3661.5	1.986e-07	0.00353	0.7022
DDX43	8530	6.292e-07	0.0112	0.6937
CXORF15	4047.5	1.117e-05	0.199	0.6708

Clinical variable #9: 'HISTOLOGICAL.TYPE'

336 genes related to 'HISTOLOGICAL.TYPE'.

Table S15. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'


HISTOLOGICAL.TYPE	Labels	N
	COLON ADENOCARCINOMA	129
	COLON MUCINOUS ADENOCARCINOMA	22
	RECTAL ADENOCARCINOMA	58
	RECTAL MUCINOUS ADENOCARCINOMA	7

	Significant markers	N = 336

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

Table S16. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

	ANOVA_P	Q
AGR2	1.439e-10	2.56e-06
PRAC	4.171e-10	7.43e-06
GPX2	4.796e-10	8.54e-06
GFI1	6.503e-10	1.16e-05
SRBD1	4.689e-09	8.35e-05
CEACAM5	5.186e-09	9.23e-05
C20ORF177	9.041e-09	0.000161
PLAGL2	9.169e-09	0.000163
HOXD8	1.076e-08	0.000192
HSP90B3P	1.28e-08	0.000228

Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

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

Table S17. Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'


COMPLETENESS.OF.RESECTION	Labels	N
	R0	185
	R1	2
	R2	29

	Significant markers	N = 0

Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

2 genes related to 'NUMBER.OF.LYMPH.NODES'.

Table S18. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'


NUMBER.OF.LYMPH.NODES	Mean (SD)	2.15 (4.7)
	Significant markers	N = 2
	pos. correlated	1
	neg. correlated	1

List of 2 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S19. Get Full Table List of 2 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

	SpearmanCorr	corrP	Q
LUZP2	0.296	7.575e-06	0.135
NFKBIZ	-0.2947	8.339e-06	0.149

Methods & Data

Input

Expresson data file = COADREAD-TP.medianexp.txt
Clinical data file = COADREAD-TP.merged_data.txt
Number of patients = 222
Number of genes = 17814
Number of clinical features = 11

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

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] 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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