Correlation between mRNAseq expression and clinical features

Liver Hepatocellular Carcinoma (Primary solid tumor)

17 October 2014 | analyses__2014_10_17

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1639NNR

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 17825 genes and 11 clinical features across 234 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 5 clinical features related to at least one genes.

35 genes correlated to 'AGE'.

RAB3D|9545 , PTK7|5754 , CDCA7|83879 , SLC44A3|126969 , PMS2L2|5380 , ...

8 genes correlated to 'NEOPLASM.DISEASESTAGE'.

TPX2|22974 , ERCC6L|54821 , CENPF|1063 , EXO1|9156 , SGOL2|151246 , ...

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

TPX2|22974 , CDCA2|157313 , SGOL2|151246 , BIRC5|332 , ERCC6L|54821 , ...

125 genes correlated to 'GENDER'.

HDHD1A|8226 , NCRNA00183|554203 , GGH|8836 , SLC25A32|81034 , NCK2|8440 , ...

115 genes correlated to 'RACE'.

XKR9|389668 , POM121L10P|646074 , TSPAN10|83882 , FAM128A|653784 , THOC3|84321 , ...

No genes correlated to 'Time to Death', 'PATHOLOGY.N.STAGE', 'PATHOLOGY.M.STAGE', 'HISTOLOGICAL.TYPE', 'COMPLETENESS.OF.RESECTION', 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=0
AGE	Spearman correlation test	N=35	older	N=17	younger	N=18
NEOPLASM DISEASESTAGE	Kruskal-Wallis test	N=8
PATHOLOGY T STAGE	Spearman correlation test	N=267	higher stage	N=185	lower stage	N=82
PATHOLOGY N STAGE	Wilcoxon test	N=0
PATHOLOGY M STAGE	Kruskal-Wallis test	N=0
GENDER	Wilcoxon test	N=125	male	N=125	female	N=0
HISTOLOGICAL TYPE	Kruskal-Wallis test	N=0
COMPLETENESS OF RESECTION	Kruskal-Wallis test	N=0
RACE	Kruskal-Wallis test	N=115
ETHNICITY	Wilcoxon 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)	0-113 (median=13.7)
	censored	N = 132
	death	N = 82

	Significant markers	N = 0

Clinical variable #2: 'AGE'

35 genes related to 'AGE'.

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


AGE	Mean (SD)	60.45 (14)
	Significant markers	N = 35
	pos. correlated	17
	neg. correlated	18

List of top 10 genes differentially expressed by 'AGE'

Table S3. Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
RAB3D\|9545	-0.348	5.606e-08	0.000999
PTK7\|5754	-0.3356	1.735e-07	0.00309
CDCA7\|83879	-0.3345	2.044e-07	0.00364
SLC44A3\|126969	-0.325	4.656e-07	0.0083
PMS2L2\|5380	0.3179	8.033e-07	0.0143
DONSON\|29980	-0.3174	8.383e-07	0.0149
FBXO46\|23403	-0.3115	1.372e-06	0.0245
FAM186B\|84070	0.3113	1.547e-06	0.0276
HAUS1\|115106	-0.3055	2.225e-06	0.0396
PRSS35\|167681	-0.3066	2.769e-06	0.0493

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

8 genes related to 'NEOPLASM.DISEASESTAGE'.

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


NEOPLASM.DISEASESTAGE	Labels	N
	STAGE I	85
	STAGE II	56
	STAGE III	2
	STAGE IIIA	51
	STAGE IIIB	6
	STAGE IIIC	9
	STAGE IV	2
	STAGE IVA	1
	STAGE IVB	2

	Significant markers	N = 8

List of 8 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S5. Get Full Table List of 8 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

	ANOVA_P	Q
TPX2\|22974	1.035e-05	0.185
ERCC6L\|54821	1.093e-05	0.195
CENPF\|1063	1.132e-05	0.202
EXO1\|9156	1.138e-05	0.203
SGOL2\|151246	1.183e-05	0.211
ANLN\|54443	1.34e-05	0.239
CENPI\|2491	1.528e-05	0.272
RACGAP1\|29127	1.648e-05	0.294

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

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

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


PATHOLOGY.T.STAGE	Mean (SD)	1.97 (0.96)
		N
	0	1
	1	93
	2	62
	3	63
	4	13

	Significant markers	N = 267
	pos. correlated	185
	neg. correlated	82

List of top 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S7. Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
TPX2\|22974	0.3781	2.678e-09	4.77e-05
CDCA2\|157313	0.378	2.697e-09	4.81e-05
SGOL2\|151246	0.3728	4.628e-09	8.25e-05
BIRC5\|332	0.3684	7.226e-09	0.000129
ERCC6L\|54821	0.3683	7.279e-09	0.00013
PRC1\|9055	0.3659	9.308e-09	0.000166
ANLN\|54443	0.3649	1.028e-08	0.000183
KIF23\|9493	0.3625	1.297e-08	0.000231
CENPF\|1063	0.3625	1.298e-08	0.000231
SLC25A25\|114789	-0.3621	1.352e-08	0.000241

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

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

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


PATHOLOGY.N.STAGE	Labels	N
	class0	146
	class1	4

	Significant markers	N = 0

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

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

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


PATHOLOGY.M.STAGE	Labels	N
	M0	163
	M1	4
	MX	67

	Significant markers	N = 0

Clinical variable #7: 'GENDER'

125 genes related to 'GENDER'.

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


GENDER	Labels	N
	FEMALE	84
	MALE	150

	Significant markers	N = 125
	Higher in MALE	125
	Higher in FEMALE	0

List of top 10 genes differentially expressed by 'GENDER'

Table S11. Get Full Table List of top 10 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
HDHD1A\|8226	2524	2.948e-14	5.25e-10	0.7997
NCRNA00183\|554203	2856	4.143e-12	7.38e-08	0.7733
GGH\|8836	9246	3.035e-09	5.4e-05	0.7338
SLC25A32\|81034	9111	1.532e-08	0.000273	0.7231
NCK2\|8440	3547	3.005e-08	0.000535	0.7185
MRPS28\|28957	9037	3.61e-08	0.000643	0.7172
PTDSS1\|9791	9036	3.652e-08	0.00065	0.7171
CNN3\|1266	9030	3.911e-08	0.000696	0.7167
MTERFD1\|51001	9018	4.483e-08	0.000798	0.7157
TMEM64\|169200	8991	6.084e-08	0.00108	0.7136

Clinical variable #8: 'HISTOLOGICAL.TYPE'

No gene related to 'HISTOLOGICAL.TYPE'.

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


HISTOLOGICAL.TYPE	Labels	N
	FIBROLAMELLAR CARCINOMA	2
	HEPATOCELLULAR CARCINOMA	227
	HEPATOCHOLANGIOCARCINOMA (MIXED)	5

	Significant markers	N = 0

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	198
	R1	13
	R2	1
	RX	16

	Significant markers	N = 0

Clinical variable #10: 'RACE'

115 genes related to 'RACE'.

Table S14. Basic characteristics of clinical feature: 'RACE'


RACE	Labels	N
	AMERICAN INDIAN OR ALASKA NATIVE	1
	ASIAN	66
	BLACK OR AFRICAN AMERICAN	15
	WHITE	143

	Significant markers	N = 115

List of top 10 genes differentially expressed by 'RACE'

Table S15. Get Full Table List of top 10 genes differentially expressed by 'RACE'

	ANOVA_P	Q
XKR9\|389668	3.609e-12	6.43e-08
POM121L10P\|646074	2.675e-11	4.77e-07
TSPAN10\|83882	1.613e-09	2.88e-05
FAM128A\|653784	2.113e-09	3.77e-05
THOC3\|84321	3.195e-09	5.69e-05
ZNF296\|162979	1.297e-08	0.000231
LDHD\|197257	5.819e-08	0.00104
PPM1K\|152926	6.905e-08	0.00123
RINL\|126432	6.996e-08	0.00125
DSCC1\|79075	8.291e-08	0.00148

Clinical variable #11: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S16. Basic characteristics of clinical feature: 'ETHNICITY'


ETHNICITY	Labels	N
	HISPANIC OR LATINO	9
	NOT HISPANIC OR LATINO	209

	Significant markers	N = 0

Methods & Data

Input

Expresson data file = LIHC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Clinical data file = LIHC-TP.merged_data.txt
Number of patients = 234
Number of genes = 17825
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

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