Correlation between mRNAseq expression and clinical features

Prostate Adenocarcinoma (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/C1PN94KH

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 18276 genes and 14 clinical features across 360 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 12 clinical features related to at least one genes.

6 genes correlated to 'AGE'.

ADAP2|55803 , SNX8|29886 , MNX1|3110 , FCGR1A|2209 , HLX|3142 , ...

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

KCNK6|9424 , CCNA2|890 , CENPA|1058 , COL10A1|1300 , ASPN|54829 , ...

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

CEP70|80321 , SPAG1|6674 , LGI3|203190 , LY6G6D|58530 , DPT|1805 , ...

14 genes correlated to 'HISTOLOGICAL.TYPE'.

RBM5|10181 , STX16|8675 , MAPK8IP3|23162 , NCRNA00204B|286967 , KCNIP2|30819 , ...

1 gene correlated to 'COMPLETENESS.OF.RESECTION'.

ZBED1|9189

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

CEP70|80321 , SPAG1|6674 , LGI3|203190 , DPT|1805 , LY6G6D|58530 , ...

1266 genes correlated to 'GLEASON_SCORE_COMBINED'.

FAM72B|653820 , FAM72D|728833 , NUF2|83540 , TROAP|10024 , PRC1|9055 , ...

1226 genes correlated to 'GLEASON_SCORE_PRIMARY'.

TROAP|10024 , FAM72B|653820 , SH3RF2|153769 , SLC22A3|6581 , C2|717 , ...

108 genes correlated to 'GLEASON_SCORE_SECONDARY'.

SLC20A1|6574 , GK|2710 , CEP78|84131 , CENPE|1062 , KIAA0319L|79932 , ...

1324 genes correlated to 'GLEASON_SCORE'.

FAM72B|653820 , FAM72D|728833 , C15ORF42|90381 , NUF2|83540 , PRC1|9055 , ...

111 genes correlated to 'PSA_RESULT_PREOP'.

DDX19B|11269 , RAB6A|5870 , KANK4|163782 , SH2D3A|10045 , TUBA4A|7277 , ...

7 genes correlated to 'PSA_VALUE'.

TFDP2|7029 , CST3|1471 , COPS7A|50813 , DUS1L|64118 , NCOA3|8202 , ...

No genes correlated to 'Time to Death', and 'RACE'.

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=6	older	N=5	younger	N=1
PATHOLOGY T STAGE	Spearman correlation test	N=508	higher stage	N=307	lower stage	N=201
PATHOLOGY N STAGE	Wilcoxon test	N=20	class1	N=20	class0	N=0
HISTOLOGICAL TYPE	Wilcoxon test	N=14	prostate adenocarcinoma acinar type	N=14	prostate adenocarcinoma other subtype	N=0
COMPLETENESS OF RESECTION	Kruskal-Wallis test	N=1
NUMBER OF LYMPH NODES	Spearman correlation test	N=30	higher number.of.lymph.nodes	N=16	lower number.of.lymph.nodes	N=14
GLEASON_SCORE_COMBINED	Spearman correlation test	N=1266	higher score	N=812	lower score	N=454
GLEASON_SCORE_PRIMARY	Spearman correlation test	N=1226	higher score	N=689	lower score	N=537
GLEASON_SCORE_SECONDARY	Spearman correlation test	N=108	higher score	N=84	lower score	N=24
GLEASON_SCORE	Spearman correlation test	N=1324	higher score	N=860	lower score	N=464
PSA_RESULT_PREOP	Spearman correlation test	N=111	higher psa_result_preop	N=42	lower psa_result_preop	N=69
PSA_VALUE	Spearman correlation test	N=7	higher psa_value	N=4	lower psa_value	N=3
RACE	Kruskal-Wallis 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)	0.3-151.4 (median=23.9)
	censored	N = 352
	death	N = 6

	Significant markers	N = 0

Clinical variable #2: 'AGE'

6 genes related to 'AGE'.

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


AGE	Mean (SD)	60.71 (6.9)
	Significant markers	N = 6
	pos. correlated	5
	neg. correlated	1

List of 6 genes differentially expressed by 'AGE'

Table S3. Get Full Table List of 6 genes significantly correlated to 'AGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
ADAP2\|55803	0.3046	5.395e-09	9.86e-05
SNX8\|29886	0.2544	1.331e-06	0.0243
MNX1\|3110	0.2455	3.592e-06	0.0656
FCGR1A\|2209	0.2387	5.952e-06	0.109
HLX\|3142	0.2295	1.366e-05	0.25
ELMO2\|63916	-0.2277	1.609e-05	0.294

Clinical variable #3: 'PATHOLOGY.T.STAGE'

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

Table S4. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'


PATHOLOGY.T.STAGE	Mean (SD)	2.6 (0.52)
		N
	2	147
	3	206
	4	5

	Significant markers	N = 508
	pos. correlated	307
	neg. correlated	201

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

Table S5. Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
KCNK6\|9424	-0.372	3.406e-13	6.23e-09
CCNA2\|890	0.3672	7.211e-13	1.32e-08
CENPA\|1058	0.3581	3.07e-12	5.61e-08
COL10A1\|1300	0.3554	4.9e-12	8.95e-08
ASPN\|54829	0.3543	5.038e-12	9.21e-08
CHRNA2\|1135	-0.3523	6.709e-12	1.23e-07
C15ORF42\|90381	0.352	6.986e-12	1.28e-07
CIT\|11113	0.3502	9.154e-12	1.67e-07
ACP2\|53	-0.3482	1.214e-11	2.22e-07
CCNE2\|9134	0.3463	1.6e-11	2.92e-07

Clinical variable #4: 'PATHOLOGY.N.STAGE'

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

Table S6. Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'


PATHOLOGY.N.STAGE	Labels	N
	class0	260
	class1	45

	Significant markers	N = 20
	Higher in class1	20
	Higher in class0	0

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

Table S7. Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'

	W(pos if higher in 'class1')	wilcoxontestP	Q	AUC
CEP70\|80321	8578	5.931e-07	0.0108	0.7332
SPAG1\|6674	8466	1.681e-06	0.0307	0.7236
LGI3\|203190	3239	1.985e-06	0.0363	0.7221
LY6G6D\|58530	2231.5	3.101e-06	0.0567	0.7389
DPT\|1805	3340	4.341e-06	0.0793	0.7145
EDN3\|1908	2823	5.666e-06	0.104	0.7232
C15ORF42\|90381	8324	5.942e-06	0.109	0.7115
KIF3A\|11127	8319	6.205e-06	0.113	0.711
AQP5\|362	3039	7.127e-06	0.13	0.7162
FAM72B\|653820	8296	7.564e-06	0.138	0.7091

Clinical variable #5: 'HISTOLOGICAL.TYPE'

14 genes related to 'HISTOLOGICAL.TYPE'.

Table S8. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'


HISTOLOGICAL.TYPE	Labels	N
	PROSTATE ADENOCARCINOMA OTHER SUBTYPE	13
	PROSTATE ADENOCARCINOMA ACINAR TYPE	347

	Significant markers	N = 14
	Higher in PROSTATE ADENOCARCINOMA ACINAR TYPE	14
	Higher in PROSTATE ADENOCARCINOMA OTHER SUBTYPE	0

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

Table S9. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

	W(pos if higher in 'PROSTATE ADENOCARCINOMA ACINAR TYPE')	wilcoxontestP	Q	AUC
RBM5\|10181	c("474", "1.334e-06")	c("474", "1.334e-06")	0.0243	0.8949
STX16\|8675	c("519", "2.447e-06")	c("519", "2.447e-06")	0.0447	0.8849
MAPK8IP3\|23162	c("536", "3.066e-06")	c("536", "3.066e-06")	0.0559	0.8812
NCRNA00204B\|286967	c("589", "6.255e-06")	c("589", "6.255e-06")	0.114	0.8691
KCNIP2\|30819	c("601", "7.126e-06")	c("601", "7.126e-06")	0.13	0.8668
PRICKLE4\|29964	c("607", "7.874e-06")	c("607", "7.874e-06")	0.144	0.8651
LY6G5B\|58496	c("614", "8.405e-06")	c("614", "8.405e-06")	0.153	0.8639
DNAH17\|8632	c("620", "9.066e-06")	c("620", "9.066e-06")	0.165	0.8626
AHSA2\|130872	c("628", "1.003e-05")	c("628", "1.003e-05")	0.183	0.8608
CCNL2\|81669	c("631", "1.041e-05")	c("631", "1.041e-05")	0.19	0.8601

Clinical variable #6: 'COMPLETENESS.OF.RESECTION'

One gene related to 'COMPLETENESS.OF.RESECTION'.

Table S10. Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'


COMPLETENESS.OF.RESECTION	Labels	N
	R0	242
	R1	89
	R2	5
	RX	10

	Significant markers	N = 1

List of one gene differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S11. Get Full Table List of one gene differentially expressed by 'COMPLETENESS.OF.RESECTION'

	ANOVA_P	Q
ZBED1\|9189	2.917e-06	0.0533

Clinical variable #7: 'NUMBER.OF.LYMPH.NODES'

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

Table S12. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'


NUMBER.OF.LYMPH.NODES	Mean (SD)	0.35 (1.3)
	Significant markers	N = 30
	pos. correlated	16
	neg. correlated	14

List of top 10 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S13. Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

	SpearmanCorr	corrP	Q
CEP70\|80321	0.2875	3.877e-07	0.00709
SPAG1\|6674	0.2812	7.088e-07	0.013
LGI3\|203190	-0.2813	7.367e-07	0.0135
DPT\|1805	-0.2766	1.089e-06	0.0199
LY6G6D\|58530	-0.2934	1.228e-06	0.0224
C15ORF42\|90381	0.2731	1.503e-06	0.0275
EDN3\|1908	-0.2749	1.92e-06	0.0351
FAM72B\|653820	0.2673	2.548e-06	0.0466
SLC2A4\|6517	-0.2644	3.294e-06	0.0602
AQP5\|362	-0.2678	3.319e-06	0.0606

Clinical variable #8: 'GLEASON_SCORE_COMBINED'

1266 genes related to 'GLEASON_SCORE_COMBINED'.

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


GLEASON_SCORE_COMBINED	Mean (SD)	7.44 (0.92)
	Significant markers	N = 1266
	pos. correlated	812
	neg. correlated	454

List of top 10 genes differentially expressed by 'GLEASON_SCORE_COMBINED'

Table S15. Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE_COMBINED' by Spearman correlation test

	SpearmanCorr	corrP	Q
FAM72B\|653820	0.4796	4.209e-22	7.69e-18
FAM72D\|728833	0.454	1.044e-19	1.91e-15
NUF2\|83540	0.4501	2.344e-19	4.28e-15
TROAP\|10024	0.4494	2.707e-19	4.95e-15
PRC1\|9055	0.4411	1.417e-18	2.59e-14
C15ORF42\|90381	0.4389	2.188e-18	4e-14
SPAG5\|10615	0.4371	3.152e-18	5.76e-14
KIF23\|9493	0.4352	4.508e-18	8.24e-14
CENPA\|1058	0.4352	5.006e-18	9.15e-14
CENPE\|1062	0.4342	5.528e-18	1.01e-13

Clinical variable #9: 'GLEASON_SCORE_PRIMARY'

1226 genes related to 'GLEASON_SCORE_PRIMARY'.

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


GLEASON_SCORE_PRIMARY	Mean (SD)	3.6 (0.62)
	Score	N
	2	1
	3	167
	4	168
	5	24

	Significant markers	N = 1226
	pos. correlated	689
	neg. correlated	537

List of top 10 genes differentially expressed by 'GLEASON_SCORE_PRIMARY'

Table S17. Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE_PRIMARY' by Spearman correlation test

	SpearmanCorr	corrP	Q
TROAP\|10024	0.4288	1.552e-17	2.84e-13
FAM72B\|653820	0.4256	2.834e-17	5.18e-13
SH3RF2\|153769	-0.4205	7.336e-17	1.34e-12
SLC22A3\|6581	-0.4193	1.016e-16	1.86e-12
C2\|717	-0.4145	2.214e-16	4.05e-12
IGSF1\|3547	-0.4166	2.7e-16	4.93e-12
FAM72D\|728833	0.4101	4.906e-16	8.96e-12
UBE2C\|11065	0.4099	5.134e-16	9.38e-12
CTHRC1\|115908	0.4062	9.877e-16	1.8e-11
TACC3\|10460	0.4047	1.282e-15	2.34e-11

Clinical variable #10: 'GLEASON_SCORE_SECONDARY'

108 genes related to 'GLEASON_SCORE_SECONDARY'.

Table S18. Basic characteristics of clinical feature: 'GLEASON_SCORE_SECONDARY'


GLEASON_SCORE_SECONDARY	Mean (SD)	3.84 (0.64)
	Score	N
	3	107
	4	202
	5	51

	Significant markers	N = 108
	pos. correlated	84
	neg. correlated	24

List of top 10 genes differentially expressed by 'GLEASON_SCORE_SECONDARY'

Table S19. Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE_SECONDARY' by Spearman correlation test

	SpearmanCorr	corrP	Q
SLC20A1\|6574	0.2955	1.089e-08	0.000199
GK\|2710	0.2832	4.566e-08	0.000834
CEP78\|84131	0.2721	1.574e-07	0.00288
CENPE\|1062	0.2717	1.641e-07	0.003
KIAA0319L\|79932	-0.2709	1.786e-07	0.00326
PTPN12\|5782	0.2704	1.889e-07	0.00345
KIF23\|9493	0.2677	2.528e-07	0.00462
CKAP2L\|150468	0.2643	3.75e-07	0.00685
NUF2\|83540	0.2622	4.518e-07	0.00825
CENPK\|64105	0.2615	5.048e-07	0.00922

Clinical variable #11: 'GLEASON_SCORE'

1324 genes related to 'GLEASON_SCORE'.

Table S20. Basic characteristics of clinical feature: 'GLEASON_SCORE'


GLEASON_SCORE	Mean (SD)	7.51 (0.95)
	Score	N
	6	31
	7	200
	8	48
	9	78
	10	3

	Significant markers	N = 1324
	pos. correlated	860
	neg. correlated	464

List of top 10 genes differentially expressed by 'GLEASON_SCORE'

Table S21. Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE' by Spearman correlation test

	SpearmanCorr	corrP	Q
FAM72B\|653820	0.4803	3.568e-22	6.52e-18
FAM72D\|728833	0.4696	3.779e-21	6.91e-17
C15ORF42\|90381	0.4574	5.136e-20	9.39e-16
NUF2\|83540	0.447	4.412e-19	8.06e-15
PRC1\|9055	0.4455	5.946e-19	1.09e-14
TROAP\|10024	0.4375	2.915e-18	5.33e-14
KIF18B\|146909	0.4369	3.268e-18	5.97e-14
KIF23\|9493	0.4361	3.809e-18	6.96e-14
SPAG5\|10615	0.4357	4.095e-18	7.48e-14
FAM72A\|729533	0.448	4.309e-18	7.87e-14

Clinical variable #12: 'PSA_RESULT_PREOP'

111 genes related to 'PSA_RESULT_PREOP'.

Table S22. Basic characteristics of clinical feature: 'PSA_RESULT_PREOP'


PSA_RESULT_PREOP	Mean (SD)	10.53 (11)
	Significant markers	N = 111
	pos. correlated	42
	neg. correlated	69

List of top 10 genes differentially expressed by 'PSA_RESULT_PREOP'

Table S23. Get Full Table List of top 10 genes significantly correlated to 'PSA_RESULT_PREOP' by Spearman correlation test

	SpearmanCorr	corrP	Q
DDX19B\|11269	-0.3014	5.908e-09	0.000108
RAB6A\|5870	0.2911	2.022e-08	0.000369
KANK4\|163782	-0.2865	3.594e-08	0.000657
SH2D3A\|10045	-0.2846	4.243e-08	0.000775
TUBA4A\|7277	-0.277	9.92e-08	0.00181
DEGS1\|8560	0.2741	1.363e-07	0.00249
C2\|717	-0.2731	1.528e-07	0.00279
FOXA3\|3171	-0.2717	1.929e-07	0.00352
IL10RB\|3588	-0.2703	2.054e-07	0.00375
FAM108B1\|51104	0.2681	2.604e-07	0.00476

Clinical variable #13: 'PSA_VALUE'

7 genes related to 'PSA_VALUE'.

Table S24. Basic characteristics of clinical feature: 'PSA_VALUE'


PSA_VALUE	Mean (SD)	0.94 (3.4)
	Significant markers	N = 7
	pos. correlated	4
	neg. correlated	3

List of 7 genes differentially expressed by 'PSA_VALUE'

Table S25. Get Full Table List of 7 genes significantly correlated to 'PSA_VALUE' by Spearman correlation test

	SpearmanCorr	corrP	Q
TFDP2\|7029	0.2715	1.216e-06	0.0222
CST3\|1471	-0.2692	1.507e-06	0.0275
COPS7A\|50813	-0.2532	6.366e-06	0.116
DUS1L\|64118	-0.2525	6.751e-06	0.123
NCOA3\|8202	0.2497	8.636e-06	0.158
ZNF675\|171392	0.2446	1.33e-05	0.243
OPRK1\|4986	0.2429	1.574e-05	0.288

Clinical variable #14: 'RACE'

No gene related to 'RACE'.

Table S26. Basic characteristics of clinical feature: 'RACE'


RACE	Labels	N
	ASIAN	2
	BLACK OR AFRICAN AMERICAN	7
	WHITE	147

	Significant markers	N = 0

Methods & Data

Input

Expresson data file = PRAD-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Clinical data file = PRAD-TP.merged_data.txt
Number of patients = 360
Number of genes = 18276
Number of clinical features = 14

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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