Correlation between mRNAseq expression and clinical features

Pancreatic Adenocarcinoma (Primary solid tumor)

16 April 2014 | analyses__2014_04_16

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/C170803M

Overview

Introduction

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

Summary

Testing the association between 18495 genes and 12 clinical features across 70 samples, statistically thresholded by Q value < 0.05, 3 clinical features related to at least one genes.

14 genes correlated to 'GENDER'.

XIST|7503 , PRKY|5616 , RPS4Y1|6192 , NLGN4Y|22829 , DDX3Y|8653 , ...

11 genes correlated to 'HISTOLOGICAL.TYPE'.

TACR2|6865 , KCNIP4|80333 , SYNM|23336 , LOC401093|401093 , MYH11|4629 , ...

65 genes correlated to 'COMPLETENESS.OF.RESECTION'.

C5ORF45|51149 , VPS39|23339 , PPAPDC3|84814 , FAM78B|149297 , PDZD4|57595 , ...

No genes correlated to 'Time to Death', 'AGE', 'NEOPLASM.DISEASESTAGE', 'PATHOLOGY.T.STAGE', 'PATHOLOGY.N.STAGE', 'PATHOLOGY.M.STAGE', 'NUMBERPACKYEARSSMOKED', 'YEAROFTOBACCOSMOKINGONSET', 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
NEOPLASM DISEASESTAGE	ANOVA test	N=0
PATHOLOGY T STAGE	Spearman correlation test	N=0
PATHOLOGY N STAGE	t test	N=0
PATHOLOGY M STAGE	ANOVA test	N=0
GENDER	t test	N=14	male	N=6	female	N=8
HISTOLOGICAL TYPE	ANOVA test	N=11
NUMBERPACKYEARSSMOKED	Spearman correlation test	N=0
YEAROFTOBACCOSMOKINGONSET	Spearman correlation test	N=0
COMPLETENESS OF RESECTION	ANOVA test	N=65
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)	0-49.4 (median=7.2)
	censored	N = 41
	death	N = 26

	Significant markers	N = 0

Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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


AGE	Mean (SD)	65.64 (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 IA	2
	STAGE IB	4
	STAGE IIA	10
	STAGE IIB	50
	STAGE III	2
	STAGE IV	2

	Significant markers	N = 0

Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

Table S4. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'


PATHOLOGY.T.STAGE	Mean (SD)	2.9 (0.46)
		N
	1	2
	2	5
	3	61
	4	2

	Significant markers	N = 0

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

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

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


PATHOLOGY.N.STAGE	Labels	N
	class0	17
	class1	52

	Significant markers	N = 0

Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

Table S6. Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'


PATHOLOGY.M.STAGE	Labels	N
	M0	37
	M1	2
	MX	31

	Significant markers	N = 0

Clinical variable #7: 'GENDER'

14 genes related to 'GENDER'.

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


GENDER	Labels	N
	FEMALE	36
	MALE	34

	Significant markers	N = 14
	Higher in MALE	6
	Higher in FEMALE	8

List of top 10 genes differentially expressed by 'GENDER'

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

	T(pos if higher in 'MALE')	ttestP	Q	AUC
XIST\|7503	-17.71	3.657e-23	6.76e-19	0.9835
PRKY\|5616	15.45	9.832e-23	1.82e-18	0.9775
RPS4Y1\|6192	23.05	2.18e-21	4.03e-17	0.9916
NLGN4Y\|22829	16.35	1.622e-17	3e-13	0.971
DDX3Y\|8653	19.43	1.02e-16	1.89e-12	0.9842
TSIX\|9383	-10.02	2.878e-13	5.32e-09	0.9962
ZFY\|7544	12.65	4.275e-13	7.9e-09	0.9654
KDM5D\|8284	11.78	2.469e-08	0.000456	0.9837
NCRNA00183\|554203	-6.03	7.896e-08	0.00146	0.8415
HDHD1A\|8226	-6.01	8.503e-08	0.00157	0.8464

Figure S1. Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 3.66e-23 with T-test analysis.

Clinical variable #8: 'HISTOLOGICAL.TYPE'

11 genes related to 'HISTOLOGICAL.TYPE'.

Table S9. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'


HISTOLOGICAL.TYPE	Labels	N
	PANCREAS-ADENOCARCINOMA DUCTAL TYPE	62
	PANCREAS-ADENOCARCINOMA-OTHER SUBTYPE	5
	PANCREAS-COLLOID (MUCINOUS NON-CYSTIC) CARCINOMA	2

	Significant markers	N = 11

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

Table S10. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

	ANOVA_P	Q
TACR2\|6865	4.371e-12	8.08e-08
KCNIP4\|80333	1.939e-10	3.58e-06
SYNM\|23336	4.551e-09	8.41e-05
LOC401093\|401093	3.149e-07	0.00582
MYH11\|4629	3.417e-07	0.00631
RGMA\|56963	6.47e-07	0.012
RIMS1\|22999	9.687e-07	0.0179
C20ORF200\|253868	1.107e-06	0.0204
CNN1\|1264	1.182e-06	0.0218
PPP1R12B\|4660	1.554e-06	0.0287

Figure S2. Get High-res Image As an example, this figure shows the association of TACR2|6865 to 'HISTOLOGICAL.TYPE'. P value = 4.37e-12 with ANOVA analysis.

Clinical variable #9: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

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


NUMBERPACKYEARSSMOKED	Mean (SD)	24.51 (14)
	Significant markers	N = 0

Clinical variable #10: 'YEAROFTOBACCOSMOKINGONSET'

No gene related to 'YEAROFTOBACCOSMOKINGONSET'.

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


YEAROFTOBACCOSMOKINGONSET	Mean (SD)	1971.74 (14)
	Significant markers	N = 0

Clinical variable #11: 'COMPLETENESS.OF.RESECTION'

65 genes related to 'COMPLETENESS.OF.RESECTION'.

Table S13. Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'


COMPLETENESS.OF.RESECTION	Labels	N
	R0	40
	R1	24
	RX	2

	Significant markers	N = 65

List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S14. Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

	ANOVA_P	Q
C5ORF45\|51149	1.816e-09	3.36e-05
VPS39\|23339	2.75e-09	5.09e-05
PPAPDC3\|84814	3.282e-09	6.07e-05
FAM78B\|149297	1.642e-08	0.000304
PDZD4\|57595	1.802e-08	0.000333
LOC144571\|144571	2.603e-08	0.000481
FBXL14\|144699	3.579e-08	0.000662
ZNF350\|59348	4.882e-08	0.000903
GAS6\|2621	4.92e-08	0.00091
NAALADL1\|10004	5.457e-08	0.00101

Figure S3. Get High-res Image As an example, this figure shows the association of C5ORF45|51149 to 'COMPLETENESS.OF.RESECTION'. P value = 1.82e-09 with ANOVA analysis.

Clinical variable #12: 'NUMBER.OF.LYMPH.NODES'

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

Table S15. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'


NUMBER.OF.LYMPH.NODES	Mean (SD)	2.91 (3.2)
	Significant markers	N = 0

Methods & Data

Input

Expresson data file = PAAD-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Clinical data file = PAAD-TP.merged_data.txt
Number of patients = 70
Number of genes = 18495
Number of clinical features = 12

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

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] 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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