Correlation between miRseq expression and clinical features

Skin Cutaneous Melanoma (Metastatic)

23 September 2013 | analyses__2013_09_23

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between miRseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1SQ8XRH

Overview

Introduction

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

Summary

Testing the association between 600 genes and 11 clinical features across 236 samples, statistically thresholded by Q value < 0.05, 3 clinical features related to at least one genes.

1 gene correlated to 'AGE'.

HSA-MIR-204

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

HSA-MIR-194-1 , HSA-MIR-205 , HSA-MIR-194-2 , HSA-MIR-342 , HSA-MIR-150 , ...

1 gene correlated to 'BRESLOW.THICKNESS'.

HSA-MIR-1537

No genes correlated to 'Time to Death', 'NEOPLASM.DISEASESTAGE', 'PATHOLOGY.T.STAGE', 'PATHOLOGY.N.STAGE', 'PATHOLOGY.M.STAGE', 'MELANOMA.ULCERATION', 'MELANOMA.PRIMARY.KNOWN', and 'GENDER'.

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=1	older	N=0	younger	N=1
PRIMARY SITE OF DISEASE	ANOVA test	N=8
NEOPLASM DISEASESTAGE	ANOVA test	N=0
PATHOLOGY T STAGE	Spearman correlation test	N=0
PATHOLOGY N STAGE	Spearman correlation test	N=0
PATHOLOGY M STAGE	ANOVA test	N=0
MELANOMA ULCERATION	t test	N=0
MELANOMA PRIMARY KNOWN	t test	N=0
BRESLOW THICKNESS	Spearman correlation test	N=1	higher breslow.thickness	N=1	lower breslow.thickness	N=0
GENDER	t 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)	0.2-357.4 (median=48.2)
	censored	N = 117
	death	N = 113

	Significant markers	N = 0

Clinical variable #2: 'AGE'

One gene related to 'AGE'.

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


AGE	Mean (SD)	55.61 (16)
	Significant markers	N = 1
	pos. correlated	0
	neg. correlated	1

List of one gene significantly correlated to 'AGE' by Spearman correlation test

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

	SpearmanCorr	corrP	Q
HSA-MIR-204	-0.2651	4.49e-05	0.0269

Figure S1. Get High-res Image As an example, this figure shows the association of HSA-MIR-204 to 'AGE'. P value = 4.49e-05 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'PRIMARY.SITE.OF.DISEASE'

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

Table S4. Basic characteristics of clinical feature: 'PRIMARY.SITE.OF.DISEASE'


PRIMARY.SITE.OF.DISEASE	Labels	N
	DISTANT METASTASIS	30
	PRIMARY TUMOR	1
	REGIONAL CUTANEOUS OR SUBCUTANEOUS TISSUE	49
	REGIONAL LYMPH NODE	155

	Significant markers	N = 8

List of 8 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

Table S5. Get Full Table List of 8 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

	ANOVA_P	Q
HSA-MIR-194-1	8.301e-06	0.00498
HSA-MIR-205	1e-05	0.00599
HSA-MIR-194-2	1.653e-05	0.00988
HSA-MIR-342	2.938e-05	0.0175
HSA-MIR-150	3.115e-05	0.0186
HSA-MIR-410	4.646e-05	0.0276
HSA-MIR-136	7.417e-05	0.0441
HSA-MIR-369	7.71e-05	0.0457

Figure S2. Get High-res Image As an example, this figure shows the association of HSA-MIR-194-1 to 'PRIMARY.SITE.OF.DISEASE'. P value = 8.3e-06 with ANOVA analysis.

Clinical variable #4: 'NEOPLASM.DISEASESTAGE'

No gene related to 'NEOPLASM.DISEASESTAGE'.

Table S6. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'


NEOPLASM.DISEASESTAGE	Labels	N
	I OR II NOS	9
	STAGE 0	4
	STAGE I	20
	STAGE IA	10
	STAGE IB	22
	STAGE II	15
	STAGE IIA	9
	STAGE IIB	12
	STAGE IIC	8
	STAGE III	19
	STAGE IIIA	10
	STAGE IIIB	21
	STAGE IIIC	38
	STAGE IV	10

	Significant markers	N = 0

Clinical variable #5: 'PATHOLOGY.T.STAGE'

No gene related to 'PATHOLOGY.T.STAGE'.

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


PATHOLOGY.T.STAGE	Mean (SD)	2.45 (1.2)
		N
	0	14
	1	27
	2	54
	3	44
	4	47

	Significant markers	N = 0

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

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

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


PATHOLOGY.N.STAGE	Mean (SD)	0.81 (1.1)
		N
	0	123
	1	38
	2	28
	3	27

	Significant markers	N = 0

Clinical variable #7: '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	207
	M1	3
	M1A	2
	M1B	2
	M1C	5

	Significant markers	N = 0

Clinical variable #8: 'MELANOMA.ULCERATION'

No gene related to 'MELANOMA.ULCERATION'.

Table S10. Basic characteristics of clinical feature: 'MELANOMA.ULCERATION'


MELANOMA.ULCERATION	Labels	N
	NO	90
	YES	59

	Significant markers	N = 0

Clinical variable #9: 'MELANOMA.PRIMARY.KNOWN'

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

Table S11. Basic characteristics of clinical feature: 'MELANOMA.PRIMARY.KNOWN'


MELANOMA.PRIMARY.KNOWN	Labels	N
	NO	30
	YES	206

	Significant markers	N = 0

Clinical variable #10: 'BRESLOW.THICKNESS'

One gene related to 'BRESLOW.THICKNESS'.

Table S12. Basic characteristics of clinical feature: 'BRESLOW.THICKNESS'


BRESLOW.THICKNESS	Mean (SD)	3.53 (5.2)
	Significant markers	N = 1
	pos. correlated	1
	neg. correlated	0

List of one gene significantly correlated to 'BRESLOW.THICKNESS' by Spearman correlation test

Table S13. Get Full Table List of one gene significantly correlated to 'BRESLOW.THICKNESS' by Spearman correlation test

	SpearmanCorr	corrP	Q
HSA-MIR-1537	0.3942	1.211e-06	0.000727

Figure S3. Get High-res Image As an example, this figure shows the association of HSA-MIR-1537 to 'BRESLOW.THICKNESS'. P value = 1.21e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #11: 'GENDER'

No gene related to 'GENDER'.

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


GENDER	Labels	N
	FEMALE	91
	MALE	145

	Significant markers	N = 0

Methods & Data

Input

Expresson data file = SKCM-TM.miRseq_RPKM_log2.txt
Clinical data file = SKCM-TM.clin.merged.picked.txt
Number of patients = 236
Number of genes = 600
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)

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