Correlation between mRNAseq expression and clinical features

Skin Cutaneous Melanoma (Metastatic)

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/C14B308G

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 18062 genes and 14 clinical features across 348 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 7 clinical features related to at least one genes.

35 genes correlated to 'AGE'.

CMBL|134147 , ACOX2|8309 , MGST2|4258 , MAOB|4129 , OR2A9P|441295 , ...

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

SHISA3|152573 , C7|730 , PAX5|5079 , CR2|1380 , FOXF1|2294 , ...

1 gene correlated to 'NEOPLASM.DISEASESTAGE'.

RAI14|26064

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

KYNU|8942 , TNFSF13B|10673 , GSDMD|79792 , INHA|3623 , ARHGAP25|9938

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

C12ORF62|84987 , MAML3|55534

27 genes correlated to 'BRESLOW.THICKNESS'.

TNFSF13B|10673 , C6ORF218|221718 , LOC100240735|100240735 , SLC7A8|23428 , FCRL6|343413 , ...

8 genes correlated to 'GENDER'.

CYORF15A|246126 , HDHD1A|8226 , NCRNA00183|554203 , CYORF15B|84663 , CA5BP|340591 , ...

No genes correlated to 'Time from Specimen Diagnosis to Death', 'Time to Death', 'PATHOLOGY.M.STAGE', 'MELANOMA.ULCERATION', 'MELANOMA.PRIMARY.KNOWN', 'RACE', 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 from Specimen Diagnosis to Death	Cox regression test	N=0
Time to Death	Cox regression test	N=0
AGE	Spearman correlation test	N=35	older	N=5	younger	N=30
PRIMARY SITE OF DISEASE	Kruskal-Wallis test	N=265
NEOPLASM DISEASESTAGE	Kruskal-Wallis test	N=1
PATHOLOGY T STAGE	Spearman correlation test	N=5	higher stage	N=0	lower stage	N=5
PATHOLOGY N STAGE	Spearman correlation test	N=2	higher stage	N=1	lower stage	N=1
PATHOLOGY M STAGE	Kruskal-Wallis test	N=0
MELANOMA ULCERATION	Wilcoxon test	N=0
MELANOMA PRIMARY KNOWN	Wilcoxon test	N=0
BRESLOW THICKNESS	Spearman correlation test	N=27	higher breslow.thickness	N=7	lower breslow.thickness	N=20
GENDER	Wilcoxon test	N=8	male	N=8	female	N=0
RACE	Kruskal-Wallis test	N=0
ETHNICITY	Wilcoxon test	N=0

Clinical variable #1: 'Time from Specimen Diagnosis to Death'

No gene related to 'Time from Specimen Diagnosis to Death'.

Table S1. Basic characteristics of clinical feature: 'Time from Specimen Diagnosis to Death'


Time from Specimen Diagnosis to Death	Duration (Months)	0.1-185.2 (median=14.6)
	censored	N = 169
	death	N = 164

	Significant markers	N = 0

Clinical variable #2: 'Time to Death'

No gene related to 'Time to Death'.

Table S2. Basic characteristics of clinical feature: 'Time to Death'


Time to Death	Duration (Months)	0.2-369.9 (median=50.1)
	censored	N = 174
	death	N = 165

	Significant markers	N = 0

Clinical variable #3: 'AGE'

35 genes related to 'AGE'.

Table S3. Basic characteristics of clinical feature: 'AGE'


AGE	Mean (SD)	56.13 (16)
	Significant markers	N = 35
	pos. correlated	5
	neg. correlated	30

List of top 10 genes differentially expressed by 'AGE'

Table S4. Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
CMBL\|134147	-0.3257	7.668e-10	1.39e-05
ACOX2\|8309	-0.3123	3.959e-09	7.15e-05
MGST2\|4258	-0.2832	1.084e-07	0.00196
MAOB\|4129	-0.2658	6.611e-07	0.0119
OR2A9P\|441295	-0.2616	1.004e-06	0.0181
NMNAT3\|349565	-0.2595	1.273e-06	0.023
LOC150568\|150568	-0.2873	1.323e-06	0.0239
LOXL4\|84171	-0.2586	1.349e-06	0.0244
CLEC1A\|51267	-0.2562	1.694e-06	0.0306
PRDX6\|9588	-0.2557	1.783e-06	0.0322

Clinical variable #4: 'PRIMARY.SITE.OF.DISEASE'

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

Table S5. Basic characteristics of clinical feature: 'PRIMARY.SITE.OF.DISEASE'


PRIMARY.SITE.OF.DISEASE	Labels	N
	DISTANT METASTASIS	60
	PRIMARY TUMOR	5
	REGIONAL CUTANEOUS OR SUBCUTANEOUS TISSUE	72
	REGIONAL LYMPH NODE	210

	Significant markers	N = 265

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

Table S6. Get Full Table List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

	ANOVA_P	Q
SHISA3\|152573	8.744e-12	1.58e-07
C7\|730	1.118e-11	2.02e-07
PAX5\|5079	5.405e-11	9.76e-07
CR2\|1380	5.76e-11	1.04e-06
FOXF1\|2294	1.313e-10	2.37e-06
MS4A1\|931	1.315e-10	2.37e-06
RBP5\|83758	1.793e-10	3.24e-06
CCL21\|6366	3.842e-10	6.94e-06
FCRL1\|115350	1.426e-09	2.58e-05
CXCR5\|643	1.487e-09	2.69e-05

Clinical variable #5: 'NEOPLASM.DISEASESTAGE'

One gene related to 'NEOPLASM.DISEASESTAGE'.

Table S7. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'


NEOPLASM.DISEASESTAGE	Labels	N
	I OR II NOS	12
	STAGE 0	7
	STAGE I	28
	STAGE IA	17
	STAGE IB	27
	STAGE II	21
	STAGE IIA	14
	STAGE IIB	19
	STAGE IIC	12
	STAGE III	35
	STAGE IIIA	15
	STAGE IIIB	32
	STAGE IIIC	59
	STAGE IV	19

	Significant markers	N = 1

List of one gene differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S8. Get Full Table List of one gene differentially expressed by 'NEOPLASM.DISEASESTAGE'

	ANOVA_P	Q
RAI14\|26064	2.339e-06	0.0423

Clinical variable #6: 'PATHOLOGY.T.STAGE'

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

Table S9. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'


PATHOLOGY.T.STAGE	Mean (SD)	2.45 (1.2)
		N
	0	23
	1	40
	2	71
	3	73
	4	68

	Significant markers	N = 5
	pos. correlated	0
	neg. correlated	5

List of 5 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S10. Get Full Table List of 5 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
KYNU\|8942	-0.2759	3.408e-06	0.0616
TNFSF13B\|10673	-0.2759	3.554e-06	0.0642
GSDMD\|79792	-0.2745	3.845e-06	0.0694
INHA\|3623	-0.2673	8.136e-06	0.147
ARHGAP25\|9938	-0.2635	9.5e-06	0.172

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

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

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


PATHOLOGY.N.STAGE	Mean (SD)	0.89 (1.1)
		N
	0	167
	1	62
	2	38
	3	47

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

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

Table S12. Get Full Table List of 2 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
C12ORF62\|84987	0.2849	2.821e-07	0.0051
MAML3\|55534	-0.2488	8.132e-06	0.147

Clinical variable #8: 'PATHOLOGY.M.STAGE'

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

Table S13. Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'


PATHOLOGY.M.STAGE	Labels	N
	M0	306
	M1	4
	M1A	3
	M1B	4
	M1C	9

	Significant markers	N = 0

Clinical variable #9: 'MELANOMA.ULCERATION'

No gene related to 'MELANOMA.ULCERATION'.

Table S14. Basic characteristics of clinical feature: 'MELANOMA.ULCERATION'


MELANOMA.ULCERATION	Labels	N
	NO	129
	YES	88

	Significant markers	N = 0

Clinical variable #10: 'MELANOMA.PRIMARY.KNOWN'

No gene related to 'MELANOMA.PRIMARY.KNOWN'.

Table S15. Basic characteristics of clinical feature: 'MELANOMA.PRIMARY.KNOWN'


MELANOMA.PRIMARY.KNOWN	Labels	N
	NO	43
	YES	304

	Significant markers	N = 0

Clinical variable #11: 'BRESLOW.THICKNESS'

27 genes related to 'BRESLOW.THICKNESS'.

Table S16. Basic characteristics of clinical feature: 'BRESLOW.THICKNESS'


BRESLOW.THICKNESS	Mean (SD)	3.53 (4.8)
	Significant markers	N = 27
	pos. correlated	7
	neg. correlated	20

List of top 10 genes differentially expressed by 'BRESLOW.THICKNESS'

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

	SpearmanCorr	corrP	Q
TNFSF13B\|10673	-0.3028	7.93e-07	0.0143
C6ORF218\|221718	0.2991	1.088e-06	0.0196
LOC100240735\|100240735	-0.3076	1.124e-06	0.0203
SLC7A8\|23428	0.2941	1.603e-06	0.0289
FCRL6\|343413	-0.2968	1.61e-06	0.0291
CRTAP\|10491	0.2904	2.191e-06	0.0396
GBP4\|115361	-0.287	2.902e-06	0.0524
ATP6V0A1\|535	0.2839	3.744e-06	0.0676
RGS18\|64407	-0.2868	4.041e-06	0.073
NMI\|9111	-0.2809	4.791e-06	0.0865

Clinical variable #12: 'GENDER'

8 genes related to 'GENDER'.

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


GENDER	Labels	N
	FEMALE	131
	MALE	217

	Significant markers	N = 8
	Higher in MALE	8
	Higher in FEMALE	0

List of 8 genes differentially expressed by 'GENDER'

Table S19. Get Full Table List of 8 genes differentially expressed by 'GENDER'. 28 significant gene(s) located in sex chromosomes is(are) filtered out.

	W(pos if higher in 'MALE')	wilcoxontestP	Q	AUC
CYORF15A\|246126	5496	2.874e-15	5.19e-11	0.9741
HDHD1A\|8226	7835	2.308e-12	4.16e-08	0.7244
NCRNA00183\|554203	8152	2.631e-11	4.75e-07	0.7132
CYORF15B\|84663	3593	7.85e-11	1.42e-06	0.974
CA5BP\|340591	9429	1.429e-07	0.00258	0.6683
MTHFD1L\|25902	18411	3.915e-06	0.0706	0.6477
PER3\|8863	18237	9.667e-06	0.174	0.6415
MED31\|51003	10199	1.012e-05	0.182	0.6412

Clinical variable #13: 'RACE'

No gene related to 'RACE'.

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


RACE	Labels	N
	ASIAN	5
	BLACK OR AFRICAN AMERICAN	1
	WHITE	325

	Significant markers	N = 0

Clinical variable #14: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S21. Basic characteristics of clinical feature: 'ETHNICITY'


ETHNICITY	Labels	N
	HISPANIC OR LATINO	7
	NOT HISPANIC OR LATINO	334

	Significant markers	N = 0

Methods & Data

Input

Expresson data file = SKCM-TM.uncv2.mRNAseq_RSEM_normalized_log2.txt
Clinical data file = SKCM-TM.merged_data.txt
Number of patients = 348
Number of genes = 18062
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

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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