Correlation between mRNAseq expression and clinical features

Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (Primary solid tumor)

15 January 2014 | analyses__2014_01_15

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1Z31X1S

Overview

Introduction

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

Summary

Testing the association between 18202 genes and 9 clinical features across 76 samples, statistically thresholded by Q value < 0.05, 3 clinical features related to at least one genes.

13 genes correlated to 'PATHOLOGY.M.STAGE'.

HOXA4|3201 , ARF1|375 , HOXA10|3206 , TRMT12|55039 , PRNP|5621 , ...

440 genes correlated to 'HISTOLOGICAL.TYPE'.

TP63|8626 , PKP1|5317 , HNF1A|6927 , LOC642587|642587 , SLC3A1|6519 , ...

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

ARMC3|219681 , APOBEC4|403314

No genes correlated to 'Time to Death', 'AGE', 'PATHOLOGY.T.STAGE', 'PATHOLOGY.N.STAGE', 'NUMBERPACKYEARSSMOKED', 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 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=0
PATHOLOGY T STAGE	Spearman correlation test	N=0
PATHOLOGY N STAGE	t test	N=0
PATHOLOGY M STAGE	ANOVA test	N=13
HISTOLOGICAL TYPE	ANOVA test	N=440
RADIATIONS RADIATION REGIMENINDICATION	t test	N=2	yes	N=2	no	N=0
NUMBERPACKYEARSSMOKED	Spearman correlation test	N=0
NUMBER OF LYMPH NODES	Spearman correlation 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)	0.1-177 (median=9.7)
	censored	N = 62
	death	N = 12

	Significant markers	N = 0

Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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


AGE	Mean (SD)	47.35 (13)
	Significant markers	N = 0

Clinical variable #3: 'PATHOLOGY.T.STAGE'

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

Table S3. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'


PATHOLOGY.T.STAGE	Mean (SD)	1.38 (0.59)
		N
	1	48
	2	22
	3	1
	4	1

	Significant markers	N = 0

Clinical variable #4: 'PATHOLOGY.N.STAGE'

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

Table S4. Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'


PATHOLOGY.N.STAGE	Labels	N
	class0	48
	class1	23

	Significant markers	N = 0

Clinical variable #5: 'PATHOLOGY.M.STAGE'

13 genes related to 'PATHOLOGY.M.STAGE'.

Table S5. Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'


PATHOLOGY.M.STAGE	Labels	N
	M0	46
	M1	2
	MX	23

	Significant markers	N = 13

List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S6. Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

	ANOVA_P	Q
HOXA4\|3201	1.888e-10	3.44e-06
ARF1\|375	3.241e-10	5.9e-06
HOXA10\|3206	8.771e-09	0.00016
TRMT12\|55039	1.401e-08	0.000255
PRNP\|5621	1.087e-07	0.00198
FAM135A\|57579	1.329e-07	0.00242
CD40\|958	4.148e-07	0.00755
SYVN1\|84447	9.003e-07	0.0164
FERMT1\|55612	1.206e-06	0.0219
AMOTL1\|154810	1.671e-06	0.0304

Figure S1. Get High-res Image As an example, this figure shows the association of HOXA4|3201 to 'PATHOLOGY.M.STAGE'. P value = 1.89e-10 with ANOVA analysis.

Clinical variable #6: 'HISTOLOGICAL.TYPE'

440 genes related to 'HISTOLOGICAL.TYPE'.

Table S7. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'


HISTOLOGICAL.TYPE	Labels	N
	CERVICAL SQUAMOUS CELL CARCINOMA	65
	ENDOCERVICAL ADENOCARCINOMA OF THE USUAL TYPE	1
	ENDOCERVICAL TYPE OF ADENOCARCINOMA	8
	ENDOMETRIOID ADENOCARCINOMA OF ENDOCERVIX	1
	MUCINOUS ADENOCARCINOMA OF ENDOCERVICAL TYPE	1

	Significant markers	N = 440

List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S8. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

	ANOVA_P	Q
TP63\|8626	6.719e-21	1.22e-16
PKP1\|5317	1.509e-18	2.74e-14
HNF1A\|6927	7.931e-18	1.44e-13
LOC642587\|642587	6.054e-17	1.1e-12
SLC3A1\|6519	1.264e-15	2.3e-11
KRT6A\|3853	1.452e-15	2.64e-11
CALML3\|810	3.883e-15	7.06e-11
GPR87\|53836	4.791e-15	8.71e-11
SLC30A2\|7780	5.469e-15	9.94e-11
DNALI1\|7802	2.013e-14	3.66e-10

Figure S2. Get High-res Image As an example, this figure shows the association of TP63|8626 to 'HISTOLOGICAL.TYPE'. P value = 6.72e-21 with ANOVA analysis.

Clinical variable #7: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S9. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'


RADIATIONS.RADIATION.REGIMENINDICATION	Labels	N
	NO	16
	YES	60

	Significant markers	N = 2
	Higher in YES	2
	Higher in NO	0

List of 2 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S10. Get Full Table List of 2 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

	T(pos if higher in 'YES')	ttestP	Q	AUC
ARMC3\|219681	6.22	2.301e-07	0.00418	0.8706
APOBEC4\|403314	5.96	1.593e-06	0.029	0.9655

Figure S3. Get High-res Image As an example, this figure shows the association of ARMC3|219681 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 2.3e-07 with T-test analysis.

Clinical variable #8: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

Table S11. Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'


NUMBERPACKYEARSSMOKED	Mean (SD)	19.24 (13)
	Significant markers	N = 0

Clinical variable #9: 'NUMBER.OF.LYMPH.NODES'

No gene related to 'NUMBER.OF.LYMPH.NODES'.

Table S12. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'


NUMBER.OF.LYMPH.NODES	Mean (SD)	0.89 (2.3)
	Significant markers	N = 0

Methods & Data

Input

Expresson data file = CESC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Clinical data file = CESC-TP.merged_data.txt
Number of patients = 76
Number of genes = 18202
Number of clinical features = 9

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

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

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

[4] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)

[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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