Breast Invasive Carcinoma: Correlation between gene methylation status and clinical features<BR>(primary solid tumor cohort)

Breast Invasive Carcinoma: Correlation between gene methylation status and clinical features
(primary solid tumor 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 17318 genes and 4 clinical features across 527 samples, statistically thresholded by Q value < 0.05, 4 clinical features related to at least one genes.

1 gene correlated to 'Time to Death'.

CDC73

131 genes correlated to 'AGE'.

KIF15 , MEX3C , LGALS8 , EGR2 , C10ORF35 , ...

191 genes correlated to 'GENDER'.

ALDOC , ZNF486 , CRIP1 , DNAJC15 , NMNAT3 , ...

224 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

CCDC86 , PRR7 , TUBA4B , CCDC85B , HS1BP3 , ...

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=1	shorter survival	N=0	longer survival	N=1
AGE	Spearman correlation test	N=131	older	N=119	younger	N=12
GENDER	t test	N=191	male	N=42	female	N=149
RADIATIONS RADIATION REGIMENINDICATION	t test	N=224	yes	N=165	no	N=59

Clinical variable #1: 'Time to Death'

One gene related to 'Time to Death'.

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


Time to Death	Duration (Months)	0-223.4 (median=18.1)
	censored	N = 441
	death	N = 58

	Significant markers	N = 1
	associated with shorter survival	0
	associated with longer survival	1

List of one gene significantly associated with 'Time to Death' by Cox regression test

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

	HazardRatio	Wald_P	Q	C_index
CDC73	0	1.411e-06	0.024	0.355

Figure S1. Get High-res Image As an example, this figure shows the association of CDC73 to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 1.41e-06 with univariate Cox regression analysis using continuous log-2 expression values.

Clinical variable #2: 'AGE'

131 genes related to 'AGE'.

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


AGE	Mean (SD)	57.6 (13)
	Significant markers	N = 131
	pos. correlated	119
	neg. correlated	12

List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

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

	SpearmanCorr	corrP	Q
KIF15	0.3161	1.139e-13	1.97e-09
MEX3C	0.2858	2.412e-11	4.18e-07
LGALS8	-0.2843	3.097e-11	5.36e-07
EGR2	0.2835	3.52e-11	6.09e-07
C10ORF35	0.2816	4.795e-11	8.3e-07
RPL13A	0.2785	7.92e-11	1.37e-06
FASN	0.2741	1.625e-10	2.81e-06
RPL27A	0.2665	5.321e-10	9.21e-06
RPL7A	0.2637	8.18e-10	1.42e-05
CACNA2D1	0.2624	9.868e-10	1.71e-05

Figure S2. Get High-res Image As an example, this figure shows the association of KIF15 to 'AGE'. P value = 1.14e-13 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'GENDER'

191 genes related to 'GENDER'.

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


GENDER	Labels	N
	FEMALE	521
	MALE	6

	Significant markers	N = 191
	Higher in MALE	42
	Higher in FEMALE	149

List of top 10 genes differentially expressed by 'GENDER'

Table S6. Get Full Table List of top 10 genes differentially expressed by 'GENDER'

	T(pos if higher in 'MALE')	ttestP	Q	AUC
ALDOC	-25.53	1.209e-92	2.09e-88	0.8669
ZNF486	-18.31	4.367e-58	7.56e-54	0.818
CRIP1	-16.85	3.091e-51	5.35e-47	0.872
DNAJC15	-13.79	8.918e-36	1.54e-31	0.7335
NMNAT3	-13.17	6.929e-34	1.2e-29	0.6916
LOC400043	-13.08	5.536e-31	9.58e-27	0.6022
RND2	-13.18	1.514e-28	2.62e-24	0.7927
EML1	-11.41	7.128e-27	1.23e-22	0.6081
SPC25	-12.19	2.831e-26	4.9e-22	0.7521
HSPC157	-12.91	7.833e-25	1.36e-20	0.6312

Figure S3. Get High-res Image As an example, this figure shows the association of ALDOC to 'GENDER'. P value = 1.21e-92 with T-test analysis.

Clinical variable #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

224 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S7. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'


RADIATIONS.RADIATION.REGIMENINDICATION	Labels	N
	NO	130
	YES	397

	Significant markers	N = 224
	Higher in YES	165
	Higher in NO	59

List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S8. Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

	T(pos if higher in 'YES')	ttestP	Q	AUC
CCDC86	7.77	1.517e-13	2.63e-09	0.7058
PRR7	7.25	3.485e-12	6.04e-08	0.6855
TUBA4B	7.14	4.371e-12	7.57e-08	0.6624
CCDC85B	7.19	5.453e-12	9.44e-08	0.6828
HS1BP3	7.04	1.148e-11	1.99e-07	0.682
TFAP4	6.96	1.633e-11	2.83e-07	0.6602
ERP29	6.84	2.699e-11	4.67e-07	0.7015
MAP1LC3B2	-6.99	2.976e-11	5.15e-07	0.6877
DDX54	6.91	3.021e-11	5.23e-07	0.6728
NDUFB4	6.91	3.406e-11	5.9e-07	0.6827

Figure S4. Get High-res Image As an example, this figure shows the association of CCDC86 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 1.52e-13 with T-test analysis.

Methods & Data

Input

Expresson data file = BRCA-TP.meth.for_correlation.filtered_data.txt
Clinical data file = BRCA-TP.clin.merged.picked.txt
Number of patients = 527
Number of genes = 17318
Number of clinical features = 4

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

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] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)

[4] 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)

Made with Nozzle