Correlation between mRNAseq expression and clinical features
Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)
16 April 2014 | analyses__2014_04_16
Maintainer Information
Citation Information
doi:10.7908/C1MK6BHN
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/C1MK6BHN
Overview
Introduction

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

Summary

Testing the association between 18029 genes and 10 clinical features across 163 samples, statistically thresholded by Q value < 0.05, 6 clinical features related to at least one genes.

- 5 genes correlated to 'AGE'.

- TNFAIP1|7126 , SLC22A18AS|5003 , HES2|54626 , SLC22A18|5002 , ADAMTS3|9508

- 419 genes correlated to 'NEOPLASM.DISEASESTAGE'.

- GPR19|2842 , PLK1|5347 , UCK2|7371 , TPX2|22974 , KIF20A|10112 , ...

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

- EPR1|8475 , BUB1|699 , UCK2|7371 , NUF2|83540 , GPR19|2842 , ...

- 1 gene correlated to 'PATHOLOGY.N.STAGE'.

- STRA6|64220

- 16 genes correlated to 'PATHOLOGY.M.STAGE'.

- IGF2BP3|10643 , PDZD2|23037 , CRELD1|78987 , HDAC11|79885 , MMP15|4324 , ...

- 57 genes correlated to 'GENDER'.

- XIST|7503 , PRKY|5616 , RPS4Y1|6192 , TSIX|9383 , KDM5C|8242 , ...

- No genes correlated to 'Time to Death', 'KARNOFSKY.PERFORMANCE.SCORE', 'NUMBERPACKYEARSSMOKED', and 'YEAROFTOBACCOSMOKINGONSET'.

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=5 | older | N=3 | younger | N=2
NEOPLASM DISEASESTAGE | ANOVA test | N=419 |  |  |  |
PATHOLOGY T STAGE | Spearman correlation test | N=320 | higher stage | N=243 | lower stage | N=77
PATHOLOGY N STAGE | Spearman correlation test | N=1 | higher stage | N=1 | lower stage | N=0
PATHOLOGY M STAGE | ANOVA test | N=16 |  |  |  |
GENDER | t test | N=57 | male | N=20 | female | N=37
KARNOFSKY PERFORMANCE SCORE | Spearman correlation test | N=0 |  |  |  |
NUMBERPACKYEARSSMOKED | Spearman correlation test | N=0 |  |  |  |
YEAROFTOBACCOSMOKINGONSET | 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) | 0-194.8 (median=14)
| censored | N = 133
| death | N = 17
| Significant markers | N = 0

Clinical variable #2: 'AGE'

5 genes related to 'AGE'.

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

AGE | Mean (SD) | 59.72 (13)
| Significant markers | N = 5
| pos. correlated | 3
| neg. correlated | 2

List of 5 genes significantly correlated to 'AGE' by Spearman correlation test

Table S3. Get Full Table List of 5 genes significantly correlated to 'AGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
TNFAIP1|7126 | -0.382 | 7.924e-07 | 0.0143
SLC22A18AS|5003 | 0.371 | 1.72e-06 | 0.031
HES2|54626 | 0.3731 | 1.881e-06 | 0.0339
SLC22A18|5002 | 0.3657 | 2.486e-06 | 0.0448
ADAMTS3|9508 | -0.3651 | 2.585e-06 | 0.0466

Figure S1. Get High-res Image As an example, this figure shows the association of TNFAIP1|7126 to 'AGE'. P value = 7.92e-07 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

419 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S4. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE | Labels | N
| STAGE I | 95
| STAGE II | 11
| STAGE III | 37
| STAGE IV | 10
| Significant markers | N = 419

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

Table S5. Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

| ANOVA_P | Q
--- | --- | ---
GPR19|2842 | 5.157e-14 | 9.3e-10
PLK1|5347 | 7.999e-14 | 1.44e-09
UCK2|7371 | 1.987e-13 | 3.58e-09
TPX2|22974 | 2.203e-13 | 3.97e-09
KIF20A|10112 | 3.452e-13 | 6.22e-09
CENPF|1063 | 6.076e-13 | 1.1e-08
NEIL3|55247 | 7.48e-13 | 1.35e-08
CDCA5|113130 | 7.637e-13 | 1.38e-08
BUB1|699 | 8.064e-13 | 1.45e-08
KIF4A|24137 | 9.209e-13 | 1.66e-08

Figure S2. Get High-res Image As an example, this figure shows the association of GPR19|2842 to 'NEOPLASM.DISEASESTAGE'. P value = 5.16e-14 with ANOVA analysis.

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

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

Table S6. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE | Mean (SD) | 1.65 (0.89)
|  | N
| 1 | 102
| 2 | 17
| 3 | 43
| 4 | 1
| Significant markers | N = 320
| pos. correlated | 243
| neg. correlated | 77

List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

Table S7. Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
EPR1|8475 | 0.5002 | 1.419e-11 | 2.56e-07
BUB1|699 | 0.4967 | 1.539e-11 | 2.77e-07
UCK2|7371 | 0.492 | 2.564e-11 | 4.62e-07
NUF2|83540 | 0.4835 | 6.274e-11 | 1.13e-06
GPR19|2842 | 0.4879 | 6.864e-11 | 1.24e-06
CDCA2|157313 | 0.4792 | 1.111e-10 | 2e-06
TPX2|22974 | 0.4735 | 1.728e-10 | 3.11e-06
PROM1|8842 | -0.4729 | 1.834e-10 | 3.31e-06
GTSE1|51512 | 0.4721 | 1.99e-10 | 3.59e-06
MAD2L1|4085 | 0.4703 | 2.381e-10 | 4.29e-06

Figure S3. Get High-res Image As an example, this figure shows the association of EPR1|8475 to 'PATHOLOGY.T.STAGE'. P value = 1.42e-11 with Spearman correlation analysis.

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

One gene related to 'PATHOLOGY.N.STAGE'.

Table S8. Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE | Mean (SD) | 0.51 (0.66)
|  | N
| 0 | 27
| 1 | 16
| 2 | 4
| Significant markers | N = 1
| pos. correlated | 1
| neg. correlated | 0

List of one gene significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

Table S9. Get Full Table List of one gene significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
STRA6|64220 | 0.6301 | 2.705e-06 | 0.0488

Figure S4. Get High-res Image As an example, this figure shows the association of STRA6|64220 to 'PATHOLOGY.N.STAGE'. P value = 2.71e-06 with Spearman correlation analysis.

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

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

Table S10. Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE | Labels | N
| M0 | 62
| M1 | 6
| MX | 82
| Significant markers | N = 16

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

Table S11. Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

| ANOVA_P | Q
--- | --- | ---
IGF2BP3|10643 | 1.079e-07 | 0.00195
PDZD2|23037 | 1.39e-07 | 0.00251
CRELD1|78987 | 2.081e-07 | 0.00375
HDAC11|79885 | 3.157e-07 | 0.00569
MMP15|4324 | 5.079e-07 | 0.00916
CA8|767 | 5.743e-07 | 0.0104
NEIL3|55247 | 7.204e-07 | 0.013
SPRYD3|84926 | 8.264e-07 | 0.0149
UGDH|7358 | 9.542e-07 | 0.0172
CCDC99|54908 | 1.136e-06 | 0.0205

Figure S5. Get High-res Image As an example, this figure shows the association of IGF2BP3|10643 to 'PATHOLOGY.M.STAGE'. P value = 1.08e-07 with ANOVA analysis.

Clinical variable #7: 'GENDER'

57 genes related to 'GENDER'.

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

GENDER | Labels | N
| FEMALE | 49
| MALE | 114
| Significant markers | N = 57
| Higher in MALE | 20
| Higher in FEMALE | 37

List of top 10 genes differentially expressed by 'GENDER'

Table S13. Get Full Table List of top 10 genes differentially expressed by 'GENDER'

| T(pos if higher in 'MALE') | ttestP | Q | AUC
--- | --- | --- | --- | ---
XIST|7503 | -20.6 | 6.067e-36 | 1.09e-31 | 0.9842
PRKY|5616 | 12.36 | 1.906e-19 | 3.44e-15 | 0.9466
RPS4Y1|6192 | 17.67 | 1.08e-18 | 1.95e-14 | 0.9698
TSIX|9383 | -11.47 | 1.003e-17 | 1.81e-13 | 0.9495
KDM5C|8242 | -9.27 | 3.649e-14 | 6.58e-10 | 0.881
NCRNA00183|554203 | -7.82 | 1.06e-11 | 1.91e-07 | 0.8369
EIF1AX|1964 | -7.45 | 1.602e-10 | 2.89e-06 | 0.8308
KDM5D|8284 | 10.98 | 8.119e-10 | 1.46e-05 | 0.9484
SYAP1|94056 | -7.01 | 9.832e-10 | 1.77e-05 | 0.8253
KDM6A|7403 | -6.77 | 1.939e-09 | 3.49e-05 | 0.8217

Figure S6. Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 6.07e-36 with T-test analysis.

Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

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

Table S14. Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE | Mean (SD) | 88.72 (18)
| Significant markers | N = 0

Clinical variable #9: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

Table S15. Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED | Mean (SD) | 36.78 (56)
| Significant markers | N = 0

Clinical variable #10: 'YEAROFTOBACCOSMOKINGONSET'

No gene related to 'YEAROFTOBACCOSMOKINGONSET'.

Table S16. Basic characteristics of clinical feature: 'YEAROFTOBACCOSMOKINGONSET'

YEAROFTOBACCOSMOKINGONSET | Mean (SD) | 1976.33 (20)
| Significant markers | N = 0

Methods & Data
Input

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

- Clinical data file = KIRP-TP.merged_data.txt

- Number of patients = 163

- Number of genes = 18029

- Number of clinical features = 10

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.

- 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] 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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