Correlation between miRseq expression and clinical features

Skin Cutaneous Melanoma (Metastatic)

23 May 2013 | analyses__2013_05_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/C1X63K14

Overview

Introduction

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

Summary

Testing the association between 602 genes and 7 clinical features across 169 samples, statistically thresholded by Q value < 0.05, 3 clinical features related to at least one genes.

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

HSA-MIR-205 , HSA-MIR-342 , HSA-MIR-150

1 gene correlated to 'DISTANT.METASTASIS'.

HSA-MIR-3654

1 gene correlated to 'LYMPH.NODE.METASTASIS'.

HSA-MIR-92A-1

No genes correlated to 'Time to Death', 'AGE', 'GENDER', and 'NEOPLASM.DISEASESTAGE'.

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
Time to Death	Cox regression test	N=0
AGE	Spearman correlation test	N=0
PRIMARY SITE OF DISEASE	ANOVA test	N=3
GENDER	t test	N=0
DISTANT METASTASIS	ANOVA test	N=1
LYMPH NODE METASTASIS	ANOVA test	N=1
NEOPLASM DISEASESTAGE	ANOVA 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=47.5)
	censored	N = 80
	death	N = 86

	Significant markers	N = 0

Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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


AGE	Mean (SD)	56.08 (16)
	Significant markers	N = 0

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

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

Table S3. Basic characteristics of clinical feature: 'PRIMARY.SITE.OF.DISEASE'


PRIMARY.SITE.OF.DISEASE	Labels	N
	DISTANT METASTASIS	24
	PRIMARY TUMOR	1
	REGIONAL CUTANEOUS OR SUBCUTANEOUS TISSUE (INCLUDES SATELLITE AND IN-TRANSIT METASTASIS)	34
	REGIONAL LYMPH NODE	110

	Significant markers	N = 3

List of 3 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

Table S4. Get Full Table List of 3 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

	ANOVA_P	Q
HSA-MIR-205	5.008e-06	0.00301
HSA-MIR-342	1.234e-05	0.00742
HSA-MIR-150	5.393e-05	0.0324

Figure S1. Get High-res Image As an example, this figure shows the association of HSA-MIR-205 to 'PRIMARY.SITE.OF.DISEASE'. P value = 5.01e-06 with ANOVA analysis.

Clinical variable #4: 'GENDER'

No gene related to 'GENDER'.

Table S5. Basic characteristics of clinical feature: 'GENDER'


GENDER	Labels	N
	FEMALE	64
	MALE	105

	Significant markers	N = 0

Clinical variable #5: 'DISTANT.METASTASIS'

One gene related to 'DISTANT.METASTASIS'.

Table S6. Basic characteristics of clinical feature: 'DISTANT.METASTASIS'


DISTANT.METASTASIS	Labels	N
	M0	146
	M1	2
	M1A	2
	M1B	2
	M1C	2

	Significant markers	N = 1

List of one gene differentially expressed by 'DISTANT.METASTASIS'

Table S7. Get Full Table List of one gene differentially expressed by 'DISTANT.METASTASIS'

	ANOVA_P	Q
HSA-MIR-3654	8.013e-05	0.048

Figure S2. Get High-res Image As an example, this figure shows the association of HSA-MIR-3654 to 'DISTANT.METASTASIS'. P value = 8.01e-05 with ANOVA analysis.

Clinical variable #6: 'LYMPH.NODE.METASTASIS'

One gene related to 'LYMPH.NODE.METASTASIS'.

Table S8. Basic characteristics of clinical feature: 'LYMPH.NODE.METASTASIS'


LYMPH.NODE.METASTASIS	Labels	N
	N0	92
	N1	2
	N1A	7
	N1B	16
	N2	1
	N2A	4
	N2B	11
	N2C	5
	N3	15
	NX	2

	Significant markers	N = 1

List of one gene differentially expressed by 'LYMPH.NODE.METASTASIS'

Table S9. Get Full Table List of one gene differentially expressed by 'LYMPH.NODE.METASTASIS'

	ANOVA_P	Q
HSA-MIR-92A-1	4.209e-05	0.0253

Figure S3. Get High-res Image As an example, this figure shows the association of HSA-MIR-92A-1 to 'LYMPH.NODE.METASTASIS'. P value = 4.21e-05 with ANOVA analysis.

Clinical variable #7: 'NEOPLASM.DISEASESTAGE'

No gene related to 'NEOPLASM.DISEASESTAGE'.

Table S10. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'


NEOPLASM.DISEASESTAGE	Labels	N
	I OR II NOS	4
	STAGE I	17
	STAGE IA	10
	STAGE IB	14
	STAGE II	18
	STAGE IIA	7
	STAGE IIB	10
	STAGE IIC	7
	STAGE III	9
	STAGE IIIA	6
	STAGE IIIB	18
	STAGE IIIC	22
	STAGE IV	6

	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 = 169
Number of genes = 602
Number of clinical features = 7

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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

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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