Correlation between mRNA expression and clinical features

Colon Adenocarcinoma (Primary solid tumor)

15 July 2014 | analyses__2014_07_15

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/C1NS0SMG

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 10 clinical features across 153 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 5 clinical features related to at least one genes.

3 genes correlated to 'AGE'.

ANAPC1 , PRSS12 , HSPH1

1 gene correlated to 'PATHOLOGY.T.STAGE'.

ALG8

5 genes correlated to 'GENDER'.

JARID1D , CYORF15A , CYORF15B , UTX , JARID1C

129 genes correlated to 'HISTOLOGICAL.TYPE'.

AGR2 , SPDEF , ALOX5 , AQP3 , SERF2 , ...

1 gene correlated to 'NUMBER.OF.LYMPH.NODES'.

PDK4

No genes correlated to 'Time to Death', 'NEOPLASM.DISEASESTAGE', 'PATHOLOGY.N.STAGE', 'PATHOLOGY.M.STAGE', 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=3	older	N=1	younger	N=2
NEOPLASM DISEASESTAGE	Kruskal-Wallis test	N=0
PATHOLOGY T STAGE	Spearman correlation test	N=1	higher stage	N=0	lower stage	N=1
PATHOLOGY N STAGE	Spearman correlation test	N=0
PATHOLOGY M STAGE	Kruskal-Wallis test	N=0
GENDER	Wilcoxon test	N=5	male	N=5	female	N=0
HISTOLOGICAL TYPE	Wilcoxon test	N=129	colon mucinous adenocarcinoma	N=129	colon adenocarcinoma	N=0
COMPLETENESS OF RESECTION	Kruskal-Wallis test	N=0
NUMBER OF LYMPH NODES	Spearman correlation test	N=1	higher number.of.lymph.nodes	N=1	lower number.of.lymph.nodes	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)	0.9-54 (median=23)
	censored	N = 115
	death	N = 26

	Significant markers	N = 0

Clinical variable #2: 'AGE'

3 genes related to 'AGE'.

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


AGE	Mean (SD)	70.78 (12)
	Significant markers	N = 3
	pos. correlated	1
	neg. correlated	2

List of 3 genes differentially expressed by 'AGE'

Table S3. Get Full Table List of 3 genes significantly correlated to 'AGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
ANAPC1	-0.388	7.19e-07	0.0128
PRSS12	0.3583	5.428e-06	0.0967
HSPH1	-0.3504	8.966e-06	0.16

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

No gene 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 = 0

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

One gene related to 'PATHOLOGY.T.STAGE'.

Table S5. 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 = 1
	pos. correlated	0
	neg. correlated	1

List of one gene differentially expressed by 'PATHOLOGY.T.STAGE'

Table S6. Get Full Table List of one gene significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
ALG8	-0.3416	1.547e-05	0.276

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'

No 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 = 0

Clinical variable #7: 'GENDER'

5 genes related to 'GENDER'.

Table S9. Basic characteristics of clinical feature: 'GENDER'


GENDER	Labels	N
	FEMALE	75
	MALE	78

	Significant markers	N = 5
	Higher in MALE	5
	Higher in FEMALE	0

List of 5 genes differentially expressed by 'GENDER'

Table S10. Get Full Table List of 5 genes differentially expressed by 'GENDER'. 22 significant gene(s) located in sex chromosomes is(are) filtered out.

	W(pos if higher in 'MALE')	wilcoxontestP	Q	AUC
JARID1D	5721	1.93e-24	3.44e-20	0.9779
CYORF15A	5589	2.456e-22	4.37e-18	0.9554
CYORF15B	5535	1.67e-21	2.97e-17	0.9462
UTX	1479	1.323e-07	0.00236	0.7472
JARID1C	1574.5	8.348e-07	0.0149	0.7309

Clinical variable #8: 'HISTOLOGICAL.TYPE'

129 genes related to 'HISTOLOGICAL.TYPE'.

Table S11. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'


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

	Significant markers	N = 129
	Higher in COLON MUCINOUS ADENOCARCINOMA	129
	Higher in COLON ADENOCARCINOMA	0

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

Table S12. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

	W(pos if higher in 'COLON MUCINOUS ADENOCARCINOMA')	wilcoxontestP	Q	AUC
AGR2	2468	3.201e-08	0.00057	0.8696
SPDEF	2448	5.809e-08	0.00103	0.8626
ALOX5	2411	1.7e-07	0.00303	0.8495
AQP3	2409	1.8e-07	0.00321	0.8488
SERF2	2398	2.458e-07	0.00438	0.845
CREB3L1	2388.5	3.208e-07	0.00571	0.8416
C20ORF177	458	4.064e-07	0.00724	0.8386
SLC19A3	464	4.796e-07	0.00854	0.8365
PTGER2	2370	5.353e-07	0.00953	0.8351
SLC39A9	2361	6.844e-07	0.0122	0.8319

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

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

Table S13. Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'


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

	Significant markers	N = 0

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

One gene related to 'NUMBER.OF.LYMPH.NODES'.

Table S14. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'


NUMBER.OF.LYMPH.NODES	Mean (SD)	2.14 (4.5)
	Significant markers	N = 1
	pos. correlated	1
	neg. correlated	0

List of one gene differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S15. Get Full Table List of one gene significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

	SpearmanCorr	corrP	Q
PDK4	0.3417	1.648e-05	0.294

Methods & Data

Input

Expresson data file = COAD-TP.medianexp.txt
Clinical data file = COAD-TP.merged_data.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)

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