Correlation between miRseq expression and clinical features

Esophageal 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 miRseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1Z31XH2

Overview

Introduction

This pipeline uses various statistical tests to identify miRs whose log2 expression levels correlated to selected clinical features.

Summary

Testing the association between 523 miRs and 9 clinical features across 150 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 5 clinical features related to at least one miRs.

5 miRs correlated to 'Time to Death'.

HSA-MIR-3648 , HSA-MIR-103-2 , HSA-MIR-1291 , HSA-MIR-505 , HSA-MIR-3653

10 miRs correlated to 'AGE'.

HSA-MIR-375 , HSA-MIR-944 , HSA-MIR-29B-2 , HSA-MIR-29B-1 , HSA-MIR-29A , ...

6 miRs correlated to 'NEOPLASM.DISEASESTAGE'.

HSA-MIR-708 , HSA-MIR-192 , HSA-MIR-194-1 , HSA-MIR-194-2 , HSA-MIR-205 , ...

8 miRs correlated to 'PATHOLOGY.T.STAGE'.

HSA-MIR-190 , HSA-MIR-206 , HSA-MIR-125B-1 , HSA-MIR-378 , HSA-MIR-556 , ...

50 miRs correlated to 'RACE'.

HSA-MIR-205 , HSA-MIR-944 , HSA-MIR-708 , HSA-MIR-149 , HSA-MIR-224 , ...

No miRs correlated to 'PATHOLOGY.N.STAGE', 'PATHOLOGY.M.STAGE', 'GENDER', 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 miRs that are significantly associated with each clinical feature at P value < 0.05 and Q value < 0.3.

Clinical feature	Statistical test	Significant miRs	Associated with		Associated with
Time to Death	Cox regression test	N=5	shorter survival	N=5	longer survival	N=0
AGE	Spearman correlation test	N=10	older	N=6	younger	N=4
NEOPLASM DISEASESTAGE	Kruskal-Wallis test	N=6
PATHOLOGY T STAGE	Spearman correlation test	N=8	higher stage	N=3	lower stage	N=5
PATHOLOGY N STAGE	Spearman correlation test	N=0
PATHOLOGY M STAGE	Kruskal-Wallis test	N=0
GENDER	Wilcoxon test	N=0
NUMBERPACKYEARSSMOKED	Spearman correlation test	N=0
RACE	Kruskal-Wallis test	N=50

Clinical variable #1: 'Time to Death'

5 miRs related to 'Time to Death'.

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


Time to Death	Duration (Months)	0-122.1 (median=7.6)
	censored	N = 87
	death	N = 55

	Significant markers	N = 5
	associated with shorter survival	5
	associated with longer survival	0

List of 5 miRs differentially expressed by 'Time to Death'

Table S2. Get Full Table List of 5 miRs significantly associated with 'Time to Death' by Cox regression test

	HazardRatio	Wald_P	Q	C_index
HSA-MIR-3648	1.26	2.88e-05	0.015	0.679
HSA-MIR-103-2	2.2	2.917e-05	0.015	0.696
HSA-MIR-1291	1.5	0.0001852	0.097	0.644
HSA-MIR-505	1.99	0.0002297	0.12	0.643
HSA-MIR-3653	1.57	0.0002493	0.13	0.648

Clinical variable #2: 'AGE'

10 miRs related to 'AGE'.

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


AGE	Mean (SD)	63.35 (12)
	Significant markers	N = 10
	pos. correlated	6
	neg. correlated	4

List of 10 miRs differentially expressed by 'AGE'

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

	SpearmanCorr	corrP	Q
HSA-MIR-375	0.3427	1.77e-05	0.00925
HSA-MIR-944	-0.3454	2.093e-05	0.0109
HSA-MIR-29B-2	0.3344	2.889e-05	0.015
HSA-MIR-29B-1	0.3326	3.195e-05	0.0166
HSA-MIR-29A	0.3195	6.758e-05	0.0351
HSA-MIR-708	-0.3127	9.788e-05	0.0507
HSA-MIR-149	-0.2976	0.0002173	0.112
HSA-MIR-147B	0.3094	0.0002217	0.114
HSA-MIR-34A	0.2865	0.0003781	0.195
HSA-MIR-193B	-0.2825	0.0004607	0.237

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

6 miRs related to 'NEOPLASM.DISEASESTAGE'.

Table S5. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'


NEOPLASM.DISEASESTAGE	Labels	N
	STAGE I	8
	STAGE IA	4
	STAGE IB	6
	STAGE II	1
	STAGE IIA	34
	STAGE IIB	26
	STAGE III	24
	STAGE IIIA	11
	STAGE IIIB	8
	STAGE IIIC	6
	STAGE IV	3
	STAGE IVA	2

	Significant markers	N = 6

List of 6 miRs differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S6. Get Full Table List of 6 miRs differentially expressed by 'NEOPLASM.DISEASESTAGE'

	ANOVA_P	Q
HSA-MIR-708	3.852e-05	0.0201
HSA-MIR-192	6.688e-05	0.0349
HSA-MIR-194-1	9.142e-05	0.0476
HSA-MIR-194-2	0.0001034	0.0537
HSA-MIR-205	0.0001782	0.0925
HSA-MIR-944	0.0004103	0.213

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

8 miRs related to 'PATHOLOGY.T.STAGE'.

Table S7. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'


PATHOLOGY.T.STAGE	Mean (SD)	2.4 (0.84)
		N
	0	1
	1	25
	2	33
	3	74
	4	4

	Significant markers	N = 8
	pos. correlated	3
	neg. correlated	5

List of 8 miRs differentially expressed by 'PATHOLOGY.T.STAGE'

Table S8. Get Full Table List of 8 miRs significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
HSA-MIR-190	-0.3591	1.638e-05	0.00856
HSA-MIR-206	-0.406	4.052e-05	0.0212
HSA-MIR-125B-1	0.3421	4.272e-05	0.0223
HSA-MIR-378	-0.3322	7.321e-05	0.0381
HSA-MIR-556	-0.3741	0.0001477	0.0766
HSA-MIR-199A-1	0.3118	0.000208	0.108
HSA-MIR-215	-0.307	0.0002637	0.136
HSA-MIR-199A-2	0.2927	0.0005176	0.267

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

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

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


PATHOLOGY.N.STAGE	Mean (SD)	0.7 (0.8)
		N
	0	63
	1	55
	2	11
	3	6

	Significant markers	N = 0

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

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

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


PATHOLOGY.M.STAGE	Labels	N
	M0	111
	M1	2
	M1A	3
	MX	17

	Significant markers	N = 0

Clinical variable #7: 'GENDER'

No miR related to 'GENDER'.

Table S11. Basic characteristics of clinical feature: 'GENDER'


GENDER	Labels	N
	FEMALE	21
	MALE	129

	Significant markers	N = 0

Clinical variable #8: 'NUMBERPACKYEARSSMOKED'

No miR related to 'NUMBERPACKYEARSSMOKED'.

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


NUMBERPACKYEARSSMOKED	Mean (SD)	35.5 (21)
	Significant markers	N = 0

Clinical variable #9: 'RACE'

50 miRs related to 'RACE'.

Table S13. Basic characteristics of clinical feature: 'RACE'


RACE	Labels	N
	ASIAN	37
	BLACK OR AFRICAN AMERICAN	2
	WHITE	93

	Significant markers	N = 50

List of top 10 miRs differentially expressed by 'RACE'

Table S14. Get Full Table List of top 10 miRs differentially expressed by 'RACE'

	ANOVA_P	Q
HSA-MIR-205	3.094e-09	1.62e-06
HSA-MIR-944	4.023e-09	2.1e-06
HSA-MIR-708	4.789e-09	2.49e-06
HSA-MIR-149	5.34e-09	2.78e-06
HSA-MIR-224	4.62e-08	2.4e-05
HSA-MIR-34B	4.62e-08	2.4e-05
HSA-MIR-193B	1.138e-07	5.88e-05
HSA-MIR-194-1	1.497e-07	7.72e-05
HSA-MIR-365-2	2.822e-07	0.000145
HSA-MIR-365-1	3.543e-07	0.000182

Methods & Data

Input

Expresson data file = ESCA-TP.miRseq_RPKM_log2.txt
Clinical data file = ESCA-TP.merged_data.txt
Number of patients = 150
Number of miRs = 523
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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