Correlation between mRNAseq expression and clinical features

Kidney Renal Clear Cell Carcinoma (Primary solid tumor)

15 January 2014 | analyses__2014_01_15

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/C1GT5KMP

Overview

Introduction

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

Summary

Testing the association between 18283 genes and 9 clinical features across 497 samples, statistically thresholded by Q value < 0.05, 6 clinical features related to at least one genes.

26 genes correlated to 'AGE'.

RANBP17|64901 , RFPL1S|10740 , WFDC1|58189 , PALLD|23022 , NEFH|4744 , ...

1573 genes correlated to 'NEOPLASM.DISEASESTAGE'.

PLEKHA9|51054 , NR3C2|4306 , IL20RB|53833 , FKBP11|51303 , UBE2C|11065 , ...

2198 genes correlated to 'PATHOLOGY.T.STAGE'.

NR3C2|4306 , ZNF132|7691 , PLEKHA9|51054 , FKBP11|51303 , FAM122A|116224 , ...

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

C11ORF34|349633 , PITX2|5308 , ATP6V1D|51382 , HEMGN|55363 , C9ORF135|138255 , ...

266 genes correlated to 'PATHOLOGY.M.STAGE'.

GARNL3|84253 , IL20RB|53833 , NFE2L3|9603 , PLEKHA9|51054 , PPIAL4G|644591 , ...

241 genes correlated to 'GENDER'.

XIST|7503 , PRKY|5616 , NLGN4Y|22829 , RPS4Y1|6192 , ZFY|7544 , ...

No genes correlated to 'Time to Death', 'KARNOFSKY.PERFORMANCE.SCORE', and 'NUMBERPACKYEARSSMOKED'.

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=26	older	N=4	younger	N=22
NEOPLASM DISEASESTAGE	ANOVA test	N=1573
PATHOLOGY T STAGE	Spearman correlation test	N=2198	higher stage	N=1188	lower stage	N=1010
PATHOLOGY N STAGE	t test	N=7	class1	N=2	class0	N=5
PATHOLOGY M STAGE	t test	N=266	m1	N=231	m0	N=35
GENDER	t test	N=241	male	N=145	female	N=96
KARNOFSKY PERFORMANCE SCORE	Spearman correlation test	N=0
NUMBERPACKYEARSSMOKED	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)	0.1-120.6 (median=36.5)
	censored	N = 335
	death	N = 162

	Significant markers	N = 0

Clinical variable #2: 'AGE'

26 genes related to 'AGE'.

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


AGE	Mean (SD)	60.71 (12)
	Significant markers	N = 26
	pos. correlated	4
	neg. correlated	22

List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

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

	SpearmanCorr	corrP	Q
RANBP17\|64901	-0.2671	1.499e-09	2.74e-05
RFPL1S\|10740	-0.2605	5.021e-09	9.18e-05
WFDC1\|58189	-0.2584	5.227e-09	9.56e-05
PALLD\|23022	-0.2445	3.497e-08	0.000639
NEFH\|4744	-0.2439	3.786e-08	0.000692
UTY\|7404	-0.2769	5.024e-08	0.000918
DIO2\|1734	-0.2332	1.541e-07	0.00282
NKAPL\|222698	-0.2236	5.009e-07	0.00915
MAPKAPK2\|9261	0.2214	6.346e-07	0.0116
ZFY\|7544	-0.2379	6.371e-07	0.0116

Figure S1. Get High-res Image As an example, this figure shows the association of RANBP17|64901 to 'AGE'. P value = 1.5e-09 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

1573 genes related to 'NEOPLASM.DISEASESTAGE'.

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


NEOPLASM.DISEASESTAGE	Labels	N
	STAGE I	240
	STAGE II	54
	STAGE III	124
	STAGE IV	79

	Significant markers	N = 1573

List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S5. Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

	ANOVA_P	Q
PLEKHA9\|51054	4.22e-17	7.72e-13
NR3C2\|4306	5.6e-17	1.02e-12
IL20RB\|53833	2.025e-16	3.7e-12
FKBP11\|51303	2.434e-16	4.45e-12
UBE2C\|11065	4.415e-16	8.07e-12
INHBE\|83729	5.022e-16	9.18e-12
ACADSB\|36	7.667e-16	1.4e-11
ALDH6A1\|4329	7.888e-16	1.44e-11
CEP55\|55165	1.414e-15	2.58e-11
UFSP2\|55325	1.957e-15	3.58e-11

Figure S2. Get High-res Image As an example, this figure shows the association of PLEKHA9|51054 to 'NEOPLASM.DISEASESTAGE'. P value = 4.22e-17 with ANOVA analysis.

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

2198 genes related to 'PATHOLOGY.T.STAGE'.

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


PATHOLOGY.T.STAGE	Mean (SD)	1.91 (0.96)
		N
	1	245
	2	65
	3	176
	4	11

	Significant markers	N = 2198
	pos. correlated	1188
	neg. correlated	1010

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

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

	SpearmanCorr	corrP	Q
NR3C2\|4306	-0.3871	3.263e-19	5.96e-15
ZNF132\|7691	-0.374	6.043e-18	1.1e-13
PLEKHA9\|51054	0.3689	1.822e-17	3.33e-13
FKBP11\|51303	0.3669	2.77e-17	5.06e-13
FAM122A\|116224	-0.3584	1.662e-16	3.04e-12
TSPAN7\|7102	-0.3558	2.823e-16	5.16e-12
TMEM150C\|441027	-0.3544	3.719e-16	6.8e-12
ANKRD56\|345079	-0.3518	6.774e-16	1.24e-11
EMCN\|51705	-0.3503	8.538e-16	1.56e-11
NOP2\|4839	0.3498	9.454e-16	1.73e-11

Figure S3. Get High-res Image As an example, this figure shows the association of NR3C2|4306 to 'PATHOLOGY.T.STAGE'. P value = 3.26e-19 with Spearman correlation analysis.

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

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

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


PATHOLOGY.N.STAGE	Labels	N
	class0	233
	class1	17

	Significant markers	N = 7
	Higher in class1	2
	Higher in class0	5

List of 7 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S9. Get Full Table List of 7 genes differentially expressed by 'PATHOLOGY.N.STAGE'

	T(pos if higher in 'class1')	ttestP	Q	AUC
C11ORF34\|349633	-7.83	3.549e-09	6.49e-05	0.7212
PITX2\|5308	6.97	1.829e-07	0.00334	0.7854
ATP6V1D\|51382	-6.26	2.918e-07	0.00533	0.7539
HEMGN\|55363	-6.02	5.129e-07	0.00937	0.7451
C9ORF135\|138255	-5.42	1.705e-06	0.0312	0.6712
AHSP\|51327	-5.92	1.921e-06	0.0351	0.7549
TMEM104\|54868	5.92	2.727e-06	0.0498	0.8051

Figure S4. Get High-res Image As an example, this figure shows the association of C11ORF34|349633 to 'PATHOLOGY.N.STAGE'. P value = 3.55e-09 with T-test analysis.

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

266 genes related to 'PATHOLOGY.M.STAGE'.

Table S10. Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'


PATHOLOGY.M.STAGE	Labels	N
	M0	419
	M1	78

	Significant markers	N = 266
	Higher in M1	231
	Higher in M0	35

List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S11. Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

	T(pos if higher in 'M1')	ttestP	Q	AUC
GARNL3\|84253	-6.85	3.696e-10	6.76e-06	0.7406
IL20RB\|53833	6.88	4.618e-10	8.44e-06	0.7341
NFE2L3\|9603	6.66	1.044e-09	1.91e-05	0.7255
PLEKHA9\|51054	6.66	1.124e-09	2.05e-05	0.7367
PPIAL4G\|644591	6.47	2.005e-09	3.67e-05	0.7012
INHBE\|83729	6.56	2.284e-09	4.17e-05	0.7266
C22ORF9\|23313	6.45	2.827e-09	5.17e-05	0.727
BIRC5\|332	6.48	3.023e-09	5.52e-05	0.7237
CEP55\|55165	6.44	4.094e-09	7.48e-05	0.7221
IGF2BP3\|10643	6.44	4.279e-09	7.82e-05	0.7296

Figure S5. Get High-res Image As an example, this figure shows the association of GARNL3|84253 to 'PATHOLOGY.M.STAGE'. P value = 3.7e-10 with T-test analysis.

Clinical variable #7: 'GENDER'

241 genes related to 'GENDER'.

Table S12. Basic characteristics of clinical feature: 'GENDER'


GENDER	Labels	N
	FEMALE	170
	MALE	327

	Significant markers	N = 241
	Higher in MALE	145
	Higher in FEMALE	96

List of top 10 genes differentially expressed by 'GENDER'

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

	T(pos if higher in 'MALE')	ttestP	Q	AUC
XIST\|7503	-45.12	4.479e-170	8.19e-166	0.9848
PRKY\|5616	40.24	2.107e-111	3.85e-107	0.9858
NLGN4Y\|22829	38.39	4.493e-85	8.21e-81	0.9852
RPS4Y1\|6192	37.13	1.222e-75	2.23e-71	0.9896
ZFY\|7544	38.1	1.778e-71	3.25e-67	0.9872
TSIX\|9383	-23.82	7.876e-71	1.44e-66	0.9645
DDX3Y\|8653	32.41	6.365e-60	1.16e-55	0.9821
KDM5C\|8242	-17.33	2.203e-51	4.03e-47	0.9007
NCRNA00183\|554203	-16.45	4.172e-46	7.62e-42	0.8646
KDM5D\|8284	26.56	2.13e-41	3.89e-37	0.9802

Figure S6. Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 4.48e-170 with T-test analysis.

Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

No gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S14. Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'


KARNOFSKY.PERFORMANCE.SCORE	Mean (SD)	90.86 (18)
	Score	N
	0	1
	70	1
	80	3
	90	13
	100	17

	Significant markers	N = 0

Clinical variable #9: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

Table S15. Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'


NUMBERPACKYEARSSMOKED	Mean (SD)	34 (16)
	Value	N
	10	1
	40	2
	46	1

	Significant markers	N = 0

Methods & Data

Input

Expresson data file = KIRC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Clinical data file = KIRC-TP.merged_data.txt
Number of patients = 497
Number of genes = 18283
Number of clinical features = 9

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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