Correlation between mRNAseq expression and clinical features
Rectum Adenocarcinoma (Primary solid tumor)
23 September 2013 | analyses__2013_09_23
Maintainer Information
Citation Information
doi:10.7908/C1T1520K
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/C1T1520K
Overview
Introduction

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

Summary

Testing the association between 18108 genes and 11 clinical features across 84 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.

- 2 genes correlated to 'NEOPLASM.DISEASESTAGE'.

- TYW3|127253 , TEKT2|27285

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

- PNMA2|10687

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

- LHFPL5|222662

- 13 genes correlated to 'GENDER'.

- XIST|7503 , PRKY|5616 , ZFY|7544 , CYORF15B|84663 , RPS4Y1|6192 , ...

- 35 genes correlated to 'HISTOLOGICAL.TYPE'.

- TMX3|54495 , LOC286467|286467 , STS|412 , ZNF271|10778 , ATP9B|374868 , ...

- 6 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

- HIST1H2AE|3012 , BEST3|144453 , HEATR4|399671 , NCRNA00173|100287569 , TRIM27|5987 , ...

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

- TAF8|129685 , BYSL|705 , MED20|9477 , MRPS10|55173 , LYG2|254773 , ...

- No genes correlated to 'Time to Death', 'AGE', 'PATHOLOGY.T.STAGE', 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=2 |  |  |  |
PATHOLOGY T STAGE | Spearman correlation test | N=0 |  |  |  |
PATHOLOGY N STAGE | Spearman correlation test | N=1 | higher stage | N=1 | lower stage | N=0
PATHOLOGY M STAGE | ANOVA test | N=1 |  |  |  |
GENDER | t test | N=13 | male | N=11 | female | N=2
HISTOLOGICAL TYPE | t test | N=35 | rectal mucinous adenocarcinoma | N=23 | rectal adenocarcinoma | N=12
RADIATIONS RADIATION REGIMENINDICATION | t test | N=6 | yes | N=2 | no | N=4
COMPLETENESS OF RESECTION | ANOVA test | N=12 |  |  |  |
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) | 0.2-129.3 (median=11.5)
| censored | N = 69
| death | N = 8
| Significant markers | N = 0

Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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

AGE | Mean (SD) | 63.4 (13)
| Significant markers | N = 0

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

2 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S3. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE | Labels | N
| STAGE I | 12
| STAGE II | 2
| STAGE IIA | 18
| STAGE IIB | 2
| STAGE IIC | 2
| STAGE III | 2
| STAGE IIIA | 7
| STAGE IIIB | 12
| STAGE IIIC | 10
| STAGE IV | 5
| STAGE IVA | 7
| Significant markers | N = 2

List of 2 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S4. Get Full Table List of 2 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

| ANOVA_P | Q
--- | --- | ---
TYW3|127253 | 3.51e-07 | 0.00636
TEKT2|27285 | 1.21e-06 | 0.0219

Figure S1. Get High-res Image As an example, this figure shows the association of TYW3|127253 to 'NEOPLASM.DISEASESTAGE'. P value = 3.51e-07 with ANOVA analysis.

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

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

Table S5. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE | Mean (SD) | 2.88 (0.65)
|  | N
| 1 | 3
| 2 | 14
| 3 | 56
| 4 | 10
| Significant markers | N = 0

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

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

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

PATHOLOGY.N.STAGE | Mean (SD) | 0.77 (0.81)
|  | N
| 0 | 38
| 1 | 24
| 2 | 19
| 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 S7. Get Full Table List of one gene significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
PNMA2|10687 | 0.4949 | 2.649e-06 | 0.048

Figure S2. Get High-res Image As an example, this figure shows the association of PNMA2|10687 to 'PATHOLOGY.N.STAGE'. P value = 2.65e-06 with Spearman correlation analysis.

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

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

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

PATHOLOGY.M.STAGE | Labels | N
| M0 | 60
| M1 | 8
| M1A | 1
| MX | 13
| Significant markers | N = 1

List of one gene differentially expressed by 'PATHOLOGY.M.STAGE'

Table S9. Get Full Table List of one gene differentially expressed by 'PATHOLOGY.M.STAGE'

| ANOVA_P | Q
--- | --- | ---
LHFPL5|222662 | 2.624e-07 | 0.00475

Figure S3. Get High-res Image As an example, this figure shows the association of LHFPL5|222662 to 'PATHOLOGY.M.STAGE'. P value = 2.62e-07 with ANOVA analysis.

Clinical variable #7: 'GENDER'

13 genes related to 'GENDER'.

Table S10. Basic characteristics of clinical feature: 'GENDER'

GENDER | Labels | N
| FEMALE | 38
| MALE | 46
| Significant markers | N = 13
| Higher in MALE | 11
| Higher in FEMALE | 2

List of top 10 genes differentially expressed by 'GENDER'

Table S11. Get Full Table List of top 10 genes differentially expressed by 'GENDER'

| T(pos if higher in 'MALE') | ttestP | Q | AUC
--- | --- | --- | --- | ---
XIST|7503 | -23.69 | 9.443e-37 | 1.71e-32 | 0.9994
PRKY|5616 | 18.15 | 1.974e-29 | 3.57e-25 | 0.9981
ZFY|7544 | 22.36 | 6.385e-28 | 1.16e-23 | 1
CYORF15B|84663 | 18.68 | 7.094e-25 | 1.28e-20 | 1
RPS4Y1|6192 | 18.61 | 4.323e-24 | 7.82e-20 | 1
DDX3Y|8653 | 23.61 | 2.83e-22 | 5.12e-18 | 1
EIF1AY|9086 | 18.28 | 2.455e-16 | 4.44e-12 | 1
TSIX|9383 | -11.12 | 1.143e-15 | 2.07e-11 | 0.9807
NLGN4Y|22829 | 20.1 | 3.217e-15 | 5.82e-11 | 1
KDM5D|8284 | 18.97 | 8.054e-15 | 1.46e-10 | 1

Figure S4. Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 9.44e-37 with T-test analysis.

Clinical variable #8: 'HISTOLOGICAL.TYPE'

35 genes related to 'HISTOLOGICAL.TYPE'.

Table S12. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE | Labels | N
| RECTAL ADENOCARCINOMA | 78
| RECTAL MUCINOUS ADENOCARCINOMA | 4
| Significant markers | N = 35
| Higher in RECTAL MUCINOUS ADENOCARCINOMA | 23
| Higher in RECTAL ADENOCARCINOMA | 12

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

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

| T(pos if higher in 'RECTAL MUCINOUS ADENOCARCINOMA') | ttestP | Q | AUC
--- | --- | --- | --- | ---
TMX3|54495 | 10.71 | 4.231e-17 | 7.27e-13 | 0.9135
LOC286467|286467 | -9.49 | 1.741e-14 | 2.99e-10 | 0.8133
STS|412 | 8.98 | 1.143e-13 | 1.96e-09 | 0.8846
ZNF271|10778 | 10.78 | 1.853e-13 | 3.18e-09 | 0.9103
ATP9B|374868 | 9.36 | 1.181e-12 | 2.03e-08 | 0.8878
ALKBH5|54890 | 9.3 | 4.453e-12 | 7.64e-08 | 0.8558
ALDH1L1|10840 | 9.69 | 4.448e-11 | 7.64e-07 | 0.8896
TMEM150B|284417 | -8.65 | 6.739e-11 | 1.16e-06 | 0.8077
MBOAT4|619373 | 9.03 | 8.481e-11 | 1.46e-06 | 0.9036
TRIM63|84676 | -8.32 | 1.277e-10 | 2.19e-06 | 0.8794

Figure S5. Get High-res Image As an example, this figure shows the association of TMX3|54495 to 'HISTOLOGICAL.TYPE'. P value = 4.23e-17 with T-test analysis.

Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S14. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N
| NO | 5
| YES | 79
| Significant markers | N = 6
| Higher in YES | 2
| Higher in NO | 4

List of 6 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S15. Get Full Table List of 6 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

| T(pos if higher in 'YES') | ttestP | Q | AUC
--- | --- | --- | --- | ---
HIST1H2AE|3012 | -7.91 | 2.554e-11 | 4.5e-07 | 0.8051
BEST3|144453 | 7.52 | 1.86e-08 | 0.000327 | 0.8828
HEATR4|399671 | -6.31 | 4.329e-08 | 0.000762 | 0.7967
NCRNA00173|100287569 | -5.59 | 4.386e-07 | 0.00772 | 0.7808
TRIM27|5987 | -8.98 | 5.908e-07 | 0.0104 | 0.9241
CTBP1|1487 | 5.43 | 1.819e-06 | 0.032 | 0.7797

Figure S6. Get High-res Image As an example, this figure shows the association of HIST1H2AE|3012 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 2.55e-11 with T-test analysis.

Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

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

Table S16. Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION | Labels | N
| R0 | 56
| R1 | 1
| R2 | 1
| RX | 4
| Significant markers | N = 12

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

Table S17. Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

| ANOVA_P | Q
--- | --- | ---
TAF8|129685 | 6.967e-11 | 1.26e-06
BYSL|705 | 6.215e-09 | 0.000112
MED20|9477 | 5.761e-08 | 0.00104
MRPS10|55173 | 6.527e-08 | 0.00118
LYG2|254773 | 8.101e-08 | 0.00146
DPY19L2P4|442523 | 2.702e-07 | 0.00489
SLC35B2|347734 | 4.427e-07 | 0.008
KRT84|3890 | 4.897e-07 | 0.00885
MAD2L1BP|9587 | 6.456e-07 | 0.0117
STS|412 | 1.119e-06 | 0.0202

Figure S7. Get High-res Image As an example, this figure shows the association of TAF8|129685 to 'COMPLETENESS.OF.RESECTION'. P value = 6.97e-11 with ANOVA analysis.

Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

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

Table S18. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES | Mean (SD) | 3.12 (5.8)
| Significant markers | N = 0

Methods & Data
Input

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

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

- Number of patients = 84

- Number of genes = 18108

- 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

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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