Skin Cutaneous Melanoma: Correlation between gene methylation status and clinical features<BR>(NRAS_Hotspot

Skin Cutaneous Melanoma: Correlation between gene methylation status and clinical features
(NRAS_Hotspot_Mutants cohort)

Maintained by Juok Cho (Broad Institute)

Overview

Introduction

This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.

Summary

Testing the association between 17071 genes and 6 clinical features across 42 samples, statistically thresholded by Q value < 0.05, 3 clinical features related to at least one genes.

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

SNX1 , ARCN1

11 genes correlated to 'LYMPH.NODE.METASTASIS'.

NUBP2 , PPCS , CRTC2 , RTKN2 , FOXL2 , ...

26 genes correlated to 'NEOPLASM.DISEASESTAGE'.

C20ORF27 , ABCA7 , PLS1 , DPEP1 , RABAC1 , ...

No genes correlated to 'Time to Death', 'AGE', 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
Time to Death	Cox regression test	N=0
AGE	Spearman correlation test	N=0
PRIMARY SITE OF DISEASE	ANOVA test	N=2
GENDER	t test	N=0
LYMPH NODE METASTASIS	ANOVA test	N=11
NEOPLASM DISEASESTAGE	ANOVA test	N=26

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)	1.1-48.8 (median=9.7)
	censored	N = 9
	death	N = 10

	Significant markers	N = 0

Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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


AGE	Mean (SD)	58.07 (15)
	Significant markers	N = 0

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

2 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	8
	REGIONAL CUTANEOUS OR SUBCUTANEOUS TISSUE (INCLUDES SATELLITE AND IN-TRANSIT METASTASIS)	9
	REGIONAL LYMPH NODE	25

	Significant markers	N = 2

List of 2 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

Table S4. Get Full Table List of 2 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

	ANOVA_P	Q
SNX1	1.93e-07	0.00329
ARCN1	2.202e-06	0.0376

Figure S1. Get High-res Image As an example, this figure shows the association of SNX1 to 'PRIMARY.SITE.OF.DISEASE'. P value = 1.93e-07 with ANOVA analysis.

Clinical variable #4: 'GENDER'

No gene related to 'GENDER'.

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


GENDER	Labels	N
	FEMALE	15
	MALE	27

	Significant markers	N = 0

Clinical variable #5: 'LYMPH.NODE.METASTASIS'

11 genes related to 'LYMPH.NODE.METASTASIS'.

Table S6. Basic characteristics of clinical feature: 'LYMPH.NODE.METASTASIS'


LYMPH.NODE.METASTASIS	Labels	N
	N0	26
	N1A	3
	N1B	4
	N2A	1
	N2B	2
	N3	3

	Significant markers	N = 11

List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

Table S7. Get Full Table List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

	ANOVA_P	Q
NUBP2	3.288e-21	5.61e-17
PPCS	2.783e-15	4.75e-11
CRTC2	2.365e-11	4.04e-07
RTKN2	9.674e-09	0.000165
FOXL2	1.025e-07	0.00175
IL20RB	1.811e-07	0.00309
AKR7L	2.994e-07	0.00511
PRG2	4.733e-07	0.00808
ZAR1L	1.363e-06	0.0233
TFIP11	1.676e-06	0.0286

Figure S2. Get High-res Image As an example, this figure shows the association of NUBP2 to 'LYMPH.NODE.METASTASIS'. P value = 3.29e-21 with ANOVA analysis.

Clinical variable #6: 'NEOPLASM.DISEASESTAGE'

26 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S8. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'


NEOPLASM.DISEASESTAGE	Labels	N
	I OR II NOS	1
	STAGE I	3
	STAGE IA	4
	STAGE IB	5
	STAGE II	4
	STAGE IIA	3
	STAGE IIB	4
	STAGE IIC	2
	STAGE III	1
	STAGE IIIA	1
	STAGE IIIB	6
	STAGE IIIC	5

	Significant markers	N = 26

List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S9. Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

	ANOVA_P	Q
C20ORF27	5.893e-38	1.01e-33
ABCA7	2.412e-29	4.12e-25
PLS1	4.38e-24	7.48e-20
DPEP1	4.515e-19	7.71e-15
RABAC1	1.64e-16	2.8e-12
DYSFIP1	1.798e-16	3.07e-12
APCDD1L	3.935e-16	6.71e-12
ZNF350	2.633e-15	4.49e-11
KIAA0146	3.187e-15	5.44e-11
TULP2	1.062e-14	1.81e-10

Figure S3. Get High-res Image As an example, this figure shows the association of C20ORF27 to 'NEOPLASM.DISEASESTAGE'. P value = 5.89e-38 with ANOVA analysis.

Methods & Data

Input

Expresson data file = SKCM-NRAS_Hotspot_Mutants.meth.for_correlation.filtered_data.txt
Clinical data file = SKCM-NRAS_Hotspot_Mutants.clin.merged.picked.txt
Number of patients = 42
Number of genes = 17071
Number of clinical features = 6

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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