Correlation between mRNAseq expression and clinical features
Prostate Adenocarcinoma (Primary solid tumor)
23 September 2013 | analyses__2013_09_23
Maintainer Information
Citation Information
doi:10.7908/C16D5RBJ
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C16D5RBJ
Overview
Introduction

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

Summary

Testing the association between 18239 genes and 5 clinical features across 161 samples, statistically thresholded by Q value < 0.05, 4 clinical features related to at least one genes.

- 1 gene correlated to 'AGE'.

- ADAP2|55803

- 9 genes correlated to 'PATHOLOGY.T.STAGE'.

- KIAA0319L|79932 , GMDS|2762 , ABAT|18 , CHRNA2|1135 , EPHX2|2053 , ...

- 4 genes correlated to 'PATHOLOGY.N.STAGE'.

- CRHR2|1395 , NKX6-2|84504 , SEC24A|10802 , PRTN3|5657

- 3 genes correlated to 'COMPLETENESS.OF.RESECTION'.

- GLP2R|9340 , MRPS6|64968 , CNGB3|54714

- No genes correlated to '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 |
--- | --- | --- | --- | --- | --- | ---
AGE | Spearman correlation test | N=1 | older | N=1 | younger | N=0
PATHOLOGY T STAGE | Spearman correlation test | N=9 | higher stage | N=2 | lower stage | N=7
PATHOLOGY N STAGE | t test | N=4 | class1 | N=1 | class0 | N=3
COMPLETENESS OF RESECTION | ANOVA test | N=3 |  |  |  |
NUMBER OF LYMPH NODES | Spearman correlation test | N=0 |  |  |  |

Clinical variable #1: 'AGE'

One gene related to 'AGE'.

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

AGE | Mean (SD) | 60.34 (6.9)
| Significant markers | N = 1
| pos. correlated | 1
| neg. correlated | 0

List of one gene significantly correlated to 'AGE' by Spearman correlation test

Table S2. Get Full Table List of one gene significantly correlated to 'AGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
ADAP2|55803 | 0.3633 | 2.343e-06 | 0.0427

Figure S1. Get High-res Image As an example, this figure shows the association of ADAP2|55803 to 'AGE'. P value = 2.34e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #2: 'PATHOLOGY.T.STAGE'

9 genes related to 'PATHOLOGY.T.STAGE'.

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

PATHOLOGY.T.STAGE | Mean (SD) | 2.6 (0.55)
|  | N
| 2 | 69
| 3 | 86
| 4 | 5
| Significant markers | N = 9
| pos. correlated | 2
| neg. correlated | 7

List of 9 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

Table S4. Get Full Table List of 9 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
KIAA0319L|79932 | -0.3928 | 2.787e-07 | 0.00508
GMDS|2762 | -0.3908 | 3.224e-07 | 0.00588
ABAT|18 | -0.3878 | 4.042e-07 | 0.00737
CHRNA2|1135 | -0.3861 | 4.612e-07 | 0.00841
EPHX2|2053 | -0.3835 | 5.55e-07 | 0.0101
TSPAN1|10103 | -0.3718 | 1.291e-06 | 0.0235
ELAVL4|1996 | 0.3912 | 1.619e-06 | 0.0295
KCNK6|9424 | -0.3648 | 2.104e-06 | 0.0384
FAM171B|165215 | 0.3629 | 2.403e-06 | 0.0438

Figure S2. Get High-res Image As an example, this figure shows the association of KIAA0319L|79932 to 'PATHOLOGY.T.STAGE'. P value = 2.79e-07 with Spearman correlation analysis.

Clinical variable #3: 'PATHOLOGY.N.STAGE'

4 genes related to 'PATHOLOGY.N.STAGE'.

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

PATHOLOGY.N.STAGE | Labels | N
| class0 | 127
| class1 | 15
| Significant markers | N = 4
| Higher in class1 | 1
| Higher in class0 | 3

List of 4 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S6. Get Full Table List of 4 genes differentially expressed by 'PATHOLOGY.N.STAGE'

| T(pos if higher in 'class1') | ttestP | Q | AUC
--- | --- | --- | --- | ---
CRHR2|1395 | -8.74 | 8.893e-08 | 0.00162 | 0.9421
NKX6-2|84504 | -6.07 | 3.342e-07 | 0.00609 | 0.8651
SEC24A|10802 | 5.72 | 1.949e-06 | 0.0355 | 0.7717
PRTN3|5657 | -6.32 | 1.989e-06 | 0.0362 | 0.783

Figure S3. Get High-res Image As an example, this figure shows the association of CRHR2|1395 to 'PATHOLOGY.N.STAGE'. P value = 8.89e-08 with T-test analysis.

Clinical variable #4: 'COMPLETENESS.OF.RESECTION'

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

Table S7. Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION | Labels | N
| R0 | 120
| R1 | 31
| RX | 3
| Significant markers | N = 3

List of 3 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S8. Get Full Table List of 3 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

| ANOVA_P | Q
--- | --- | ---
GLP2R|9340 | 6.285e-10 | 1.15e-05
MRPS6|64968 | 9.64e-07 | 0.0176
CNGB3|54714 | 1.7e-06 | 0.031

Figure S4. Get High-res Image As an example, this figure shows the association of GLP2R|9340 to 'COMPLETENESS.OF.RESECTION'. P value = 6.28e-10 with ANOVA analysis.

Clinical variable #5: 'NUMBER.OF.LYMPH.NODES'

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

Table S9. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES | Mean (SD) | 0.2 (0.73)
| Significant markers | N = 0

Methods & Data
Input

- Expresson data file = PRAD-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt

- Clinical data file = PRAD-TP.clin.merged.picked.txt

- Number of patients = 161

- Number of genes = 18239

- Number of clinical features = 5

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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

References
[1] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)
[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[3] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[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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