Correlation between mRNA expression and clinical features

Rectum Adenocarcinoma (Primary solid tumor)

02 April 2015 | analyses__2015_04_02

Maintainer Information

Citation Information

Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)

Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Correlation between mRNA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1VX0FK4

Overview

Introduction

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

Summary

Testing the association between 17814 genes and 10 clinical features across 69 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 3 clinical features related to at least one genes.

8 genes correlated to 'PATHOLOGY_T_STAGE'.

SQLE , DULLARD , TMEM55A , DDX20 , ALDH3A2 , ...

5 genes correlated to 'GENDER'.

JARID1D , CYORF15A , CYORF15B , HDHD1A , UTX

30 genes correlated to 'HISTOLOGICAL_TYPE'.

TLE6 , CAMK2N1 , TTLL7 , AGR2 , MYOM3 , ...

No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'YEARS_TO_BIRTH', 'NEOPLASM_DISEASESTAGE', 'PATHOLOGY_N_STAGE', 'PATHOLOGY_M_STAGE', 'COMPLETENESS_OF_RESECTION', and 'NUMBER_OF_LYMPH_NODES'.

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 P value < 0.05 and Q value < 0.3.

Clinical feature	Statistical test	Significant genes	Associated with		Associated with
DAYS_TO_DEATH_OR_LAST_FUP	Cox regression test	N=0
YEARS_TO_BIRTH	Spearman correlation test	N=0
NEOPLASM_DISEASESTAGE	Kruskal-Wallis test	N=0
PATHOLOGY_T_STAGE	Spearman correlation test	N=8	higher stage	N=2	lower stage	N=6
PATHOLOGY_N_STAGE	Spearman correlation test	N=0
PATHOLOGY_M_STAGE	Wilcoxon test	N=0
GENDER	Wilcoxon test	N=5	male	N=5	female	N=0
HISTOLOGICAL_TYPE	Wilcoxon test	N=30	rectal mucinous adenocarcinoma	N=30	rectal adenocarcinoma	N=0
COMPLETENESS_OF_RESECTION	Kruskal-Wallis test	N=0
NUMBER_OF_LYMPH_NODES	Spearman correlation test	N=0

Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

No gene related to 'DAYS_TO_DEATH_OR_LAST_FUP'.

Table S1. Basic characteristics of clinical feature: 'DAYS_TO_DEATH_OR_LAST_FUP'


DAYS_TO_DEATH_OR_LAST_FUP	Duration (Months)	1-52 (median=20)
	censored	N = 59
	death	N = 9

	Significant markers	N = 0

Clinical variable #2: 'YEARS_TO_BIRTH'

No gene related to 'YEARS_TO_BIRTH'.

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


YEARS_TO_BIRTH	Mean (SD)	66.64 (11)
	Significant markers	N = 0

Clinical variable #3: 'NEOPLASM_DISEASESTAGE'

No gene related to 'NEOPLASM_DISEASESTAGE'.

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


NEOPLASM_DISEASESTAGE	Labels	N
	STAGE I	18
	STAGE II	3
	STAGE IIA	20
	STAGE III	2
	STAGE IIIB	10
	STAGE IIIC	4
	STAGE IV	12

	Significant markers	N = 0

Clinical variable #4: 'PATHOLOGY_T_STAGE'

8 genes related to 'PATHOLOGY_T_STAGE'.

Table S4. Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'


PATHOLOGY_T_STAGE	Mean (SD)	2.7 (0.69)
		N
	T1	5
	T2	15
	T3	45
	T4	4

	Significant markers	N = 8
	pos. correlated	2
	neg. correlated	6

List of 8 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S5. Get Full Table List of 8 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
SQLE	0.5181	5.122e-06	0.0912
DULLARD	-0.4732	4.028e-05	0.283
TMEM55A	0.4692	4.762e-05	0.283
DDX20	-0.4583	7.498e-05	0.284
ALDH3A2	-0.4494	0.0001074	0.284
TSR1	-0.4473	0.0001166	0.284
PITPNA	-0.4463	0.0001214	0.284
EIF4A1	-0.445	0.0001277	0.284

Clinical variable #5: 'PATHOLOGY_N_STAGE'

No gene related to 'PATHOLOGY_N_STAGE'.

Table S6. Basic characteristics of clinical feature: 'PATHOLOGY_N_STAGE'


PATHOLOGY_N_STAGE	Mean (SD)	0.57 (0.78)
		N
	N0	42
	N1	15
	N2	12

	Significant markers	N = 0

Clinical variable #6: 'PATHOLOGY_M_STAGE'

No gene related to 'PATHOLOGY_M_STAGE'.

Table S7. Basic characteristics of clinical feature: 'PATHOLOGY_M_STAGE'


PATHOLOGY_M_STAGE	Labels	N
	class0	57
	class1	12

	Significant markers	N = 0

Clinical variable #7: 'GENDER'

5 genes related to 'GENDER'.

Table S8. Basic characteristics of clinical feature: 'GENDER'


GENDER	Labels	N
	FEMALE	31
	MALE	38

	Significant markers	N = 5
	Higher in MALE	5
	Higher in FEMALE	0

List of 5 genes differentially expressed by 'GENDER'

Table S9. Get Full Table List of 5 genes differentially expressed by 'GENDER'. 18 significant gene(s) located in sex chromosomes is(are) filtered out.

	W(pos if higher in 'MALE')	wilcoxontestP	Q	AUC
JARID1D	1117	1.972e-10	8.22e-07	0.9482
CYORF15A	1115	2.308e-10	8.22e-07	0.9465
CYORF15B	1066	9.02e-09	2.01e-05	0.9049
HDHD1A	192	1.726e-06	0.00279	0.837
UTX	286	0.0002631	0.229	0.7572

Clinical variable #8: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

Table S10. Basic characteristics of clinical feature: 'HISTOLOGICAL_TYPE'


HISTOLOGICAL_TYPE	Labels	N
	RECTAL ADENOCARCINOMA	58
	RECTAL MUCINOUS ADENOCARCINOMA	7

	Significant markers	N = 30
	Higher in RECTAL MUCINOUS ADENOCARCINOMA	30
	Higher in RECTAL ADENOCARCINOMA	0

List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S11. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

	W(pos if higher in 'RECTAL MUCINOUS ADENOCARCINOMA')	wilcoxontestP	Q	AUC
TLE6	399	3.516e-05	0.218	0.9828
CAMK2N1	20	0.0001124	0.218	0.9507
TTLL7	384	0.0001336	0.218	0.9458
AGR2	383	0.0001455	0.218	0.9433
MYOM3	24	0.0001585	0.218	0.9409
BCL2L1	25	0.0001725	0.218	0.9384
FHL2	377	0.000241	0.218	0.9286
CBR3	376	0.0002618	0.218	0.9261
CREB3L4	374	0.0003084	0.218	0.9212
TOX	374	0.0003084	0.218	0.9212

Clinical variable #9: 'COMPLETENESS_OF_RESECTION'

No gene related to 'COMPLETENESS_OF_RESECTION'.

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


COMPLETENESS_OF_RESECTION	Labels	N
	R0	57
	R1	1
	R2	10

	Significant markers	N = 0

Clinical variable #10: 'NUMBER_OF_LYMPH_NODES'

No gene related to 'NUMBER_OF_LYMPH_NODES'.

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


NUMBER_OF_LYMPH_NODES	Mean (SD)	2.19 (5.1)
	Significant markers	N = 0

Methods & Data

Input

Expresson data file = READ-TP.medianexp.txt
Clinical data file = READ-TP.merged_data.txt
Number of patients = 69
Number of genes = 17814
Number of clinical features = 10

Selected clinical features

For clinical features selected for this analysis and their value conozzle.versions, please find a documentation on selected CDEs .
Survival time data

Survival time data is a combined value of days_to_death and days_to_last_followup. For each patient, it creates a combined value 'days_to_death_or_last_fup' using conversion process below.

if 'vital_status'==1(dead), 'days_to_last_followup' is always NA. Thus, uses 'days_to_death' value for 'days_to_death_or_fup'

if 'vital_status'==0(alive),

if 'days_to_death'==NA & 'days_to_last_followup'!=NA, uses 'days_to_last_followup' value for 'days_to_death_or_fup'

if 'days_to_death'!=NA, excludes this case in survival analysis and report the case.

if 'vital_status'==NA,excludes this case in survival analysis and report the case.

cf. In certain diesase types such as SKCM, days_to_death parameter is replaced with time_from_specimen_dx or time_from_specimen_procurement_to_death .

This analysis excluded clinical variables that has only NA values.

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

Wilcoxon rank sum test (Mann-Whitney U test)

For two groups (mutant or wild-type) of continuous type of clinical data, wilcoxon rank sum test (Mann and Whitney, 1947) was applied to compare their mean difference using 'wilcox.test(continuous.clinical ~ as.factor(group), exact=FALSE)' function in R. This test is equivalent to the Mann-Whitney test.

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] Mann and Whitney, On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other, Annals of Mathematical Statistics 18 (1), 50-60 (1947)

[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)

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