Correlation between mRNAseq expression and clinical features
Bladder Urothelial Carcinoma (Primary solid tumor)
22 February 2013 | analyses__2013_02_22
Maintainer Information
Citation Information
doi:10.7908/C18K7773
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/C18K7773
Overview
Introduction

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

Summary

Testing the association between 18283 genes and 11 clinical features across 115 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

- 10 genes correlated to 'GENDER'.

- USP9Y|8287 , PRKY|5616 , CYORF15A|246126 , XIST|7503 , RPS4Y1|6192 , ...

- 1 gene correlated to 'DISTANT.METASTASIS'.

- C9ORF70|84850

- 2 genes correlated to 'LYMPH.NODE.METASTASIS'.

- TRIM25|7706 , C17ORF78|284099

- 13 genes correlated to 'NUMBER.OF.LYMPH.NODES'.

- BAT2|7916 , FBXO5|26271 , MYH14|79784 , EFNA1|1942 , PRR15L|79170 , ...

- 11 genes correlated to 'NEOPLASM.DISEASESTAGE'.

- LIMD1|8994 , BAAT|570 , SLC39A5|283375 , LOC55908|55908 , PXT1|222659 , ...

- No genes correlated to 'Time to Death', 'AGE', 'KARNOFSKY.PERFORMANCE.SCORE', 'NUMBERPACKYEARSSMOKED', 'STOPPEDSMOKINGYEAR', and 'TOBACCOSMOKINGHISTORYINDICATOR'.

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 |  |  |  |
GENDER | t test | N=10 | male | N=8 | female | N=2
KARNOFSKY PERFORMANCE SCORE | Spearman correlation test | N=0 |  |  |  |
NUMBERPACKYEARSSMOKED | Spearman correlation test | N=0 |  |  |  |
STOPPEDSMOKINGYEAR | Spearman correlation test | N=0 |  |  |  |
TOBACCOSMOKINGHISTORYINDICATOR | Spearman correlation test | N=0 |  |  |  |
DISTANT METASTASIS | ANOVA test | N=1 |  |  |  |
LYMPH NODE METASTASIS | ANOVA test | N=2 |  |  |  |
NUMBER OF LYMPH NODES | Spearman correlation test | N=13 | higher number.of.lymph.nodes | N=9 | lower number.of.lymph.nodes | N=4
NEOPLASM DISEASESTAGE | ANOVA test | N=11 |  |  |  |

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) | 0.1-131.2 (median=7)
| censored | N = 78
| death | N = 30
| Significant markers | N = 0

Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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

AGE | Mean (SD) | 66.83 (11)
| Significant markers | N = 0

Clinical variable #3: 'GENDER'

10 genes related to 'GENDER'.

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

GENDER | Labels | N
| FEMALE | 32
| MALE | 83
| Significant markers | N = 10
| Higher in MALE | 8
| Higher in FEMALE | 2

List of 10 genes differentially expressed by 'GENDER'

Table S4. Get Full Table List of 10 genes differentially expressed by 'GENDER'

| T(pos if higher in 'MALE') | ttestP | Q | AUC
--- | --- | --- | --- | ---
USP9Y|8287 | 34.24 | 3.088e-44 | 5.64e-40 | 1
PRKY|5616 | 23.54 | 9.556e-37 | 1.75e-32 | 0.998
CYORF15A|246126 | 29.79 | 2.894e-32 | 5.29e-28 | 1
XIST|7503 | -19.34 | 7.872e-32 | 1.44e-27 | 0.9898
RPS4Y1|6192 | 39.54 | 6.257e-31 | 1.14e-26 | 1
KDM5D|8284 | 38.45 | 1.382e-30 | 2.52e-26 | 1
DDX3Y|8653 | 33.93 | 9.609e-26 | 1.75e-21 | 1
ZFY|7544 | 26.52 | 1.458e-24 | 2.66e-20 | 1
NLGN4Y|22829 | 17.81 | 5.045e-22 | 9.21e-18 | 0.9874
TSIX|9383 | -15.04 | 9.24e-22 | 1.69e-17 | 0.9832

Figure S1. Get High-res Image As an example, this figure shows the association of USP9Y|8287 to 'GENDER'. P value = 3.09e-44 with T-test analysis.

Clinical variable #4: 'KARNOFSKY.PERFORMANCE.SCORE'

No gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S5. Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE | Mean (SD) | 77.65 (17)
| Significant markers | N = 0

Clinical variable #5: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED | Mean (SD) | 35.33 (23)
| Significant markers | N = 0

Clinical variable #6: 'STOPPEDSMOKINGYEAR'

No gene related to 'STOPPEDSMOKINGYEAR'.

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

STOPPEDSMOKINGYEAR | Mean (SD) | 1991.55 (17)
| Significant markers | N = 0

Clinical variable #7: 'TOBACCOSMOKINGHISTORYINDICATOR'

No gene related to 'TOBACCOSMOKINGHISTORYINDICATOR'.

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

TOBACCOSMOKINGHISTORYINDICATOR | Mean (SD) | 2.61 (1.1)
| Value | N
| 1 | 26
| 2 | 21
| 3 | 34
| 4 | 26
| 5 | 2
| Significant markers | N = 0

Clinical variable #8: 'DISTANT.METASTASIS'

One gene related to 'DISTANT.METASTASIS'.

Table S9. Basic characteristics of clinical feature: 'DISTANT.METASTASIS'

DISTANT.METASTASIS | Labels | N
| M0 | 69
| M1 | 3
| MX | 42
| Significant markers | N = 1

List of one gene differentially expressed by 'DISTANT.METASTASIS'

Table S10. Get Full Table List of one gene differentially expressed by 'DISTANT.METASTASIS'

| ANOVA_P | Q
--- | --- | ---
C9ORF70|84850 | 1.865e-07 | 0.00341

Figure S2. Get High-res Image As an example, this figure shows the association of C9ORF70|84850 to 'DISTANT.METASTASIS'. P value = 1.86e-07 with ANOVA analysis.

Clinical variable #9: 'LYMPH.NODE.METASTASIS'

2 genes related to 'LYMPH.NODE.METASTASIS'.

Table S11. Basic characteristics of clinical feature: 'LYMPH.NODE.METASTASIS'

LYMPH.NODE.METASTASIS | Labels | N
| N0 | 67
| N1 | 11
| N2 | 22
| N3 | 4
| NX | 9
| Significant markers | N = 2

List of 2 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

Table S12. Get Full Table List of 2 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

| ANOVA_P | Q
--- | --- | ---
TRIM25|7706 | 5.055e-08 | 0.000924
C17ORF78|284099 | 1.932e-06 | 0.0353

Figure S3. Get High-res Image As an example, this figure shows the association of TRIM25|7706 to 'LYMPH.NODE.METASTASIS'. P value = 5.06e-08 with ANOVA analysis.

Clinical variable #10: 'NUMBER.OF.LYMPH.NODES'

13 genes related to 'NUMBER.OF.LYMPH.NODES'.

Table S13. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES | Mean (SD) | 1.92 (3.9)
| Significant markers | N = 13
| pos. correlated | 9
| neg. correlated | 4

List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

Table S14. Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
BAT2|7916 | -0.5294 | 1.599e-07 | 0.00292
FBXO5|26271 | -0.5275 | 1.803e-07 | 0.0033
MYH14|79784 | 0.525 | 2.109e-07 | 0.00386
EFNA1|1942 | 0.5175 | 3.359e-07 | 0.00614
PRR15L|79170 | 0.5138 | 4.21e-07 | 0.00769
C6ORF141|135398 | -0.5142 | 1.065e-06 | 0.0195
ANXA9|8416 | 0.4917 | 1.527e-06 | 0.0279
TMED3|23423 | 0.4905 | 1.631e-06 | 0.0298
NPHP4|261734 | -0.4882 | 1.86e-06 | 0.034
LGALS3|3958 | 0.4855 | 2.161e-06 | 0.0395

Figure S4. Get High-res Image As an example, this figure shows the association of BAT2|7916 to 'NUMBER.OF.LYMPH.NODES'. P value = 1.6e-07 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #11: 'NEOPLASM.DISEASESTAGE'

11 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S15. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE | Labels | N
| STAGE I | 1
| STAGE II | 34
| STAGE III | 37
| STAGE IV | 39
| Significant markers | N = 11

List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S16. Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

| ANOVA_P | Q
--- | --- | ---
LIMD1|8994 | 7.683e-09 | 0.00014
BAAT|570 | 8.368e-09 | 0.000153
SLC39A5|283375 | 9.408e-09 | 0.000172
LOC55908|55908 | 1.144e-07 | 0.00209
PXT1|222659 | 1.249e-07 | 0.00228
FAM35B2|439965 | 5.91e-07 | 0.0108
TTC36|143941 | 1.051e-06 | 0.0192
TRIM25|7706 | 1.127e-06 | 0.0206
POMT2|29954 | 2.089e-06 | 0.0382
SACM1L|22908 | 2.62e-06 | 0.0479

Figure S5. Get High-res Image As an example, this figure shows the association of LIMD1|8994 to 'NEOPLASM.DISEASESTAGE'. P value = 7.68e-09 with ANOVA analysis.

Methods & Data
Input

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

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

- Number of patients = 115

- Number of genes = 18283

- Number of clinical features = 11

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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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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