Correlation between RPPA expression and clinical features
Thyroid Adenocarcinoma (Primary solid tumor)
23 September 2013 | analyses__2013_09_23
Maintainer Information
Citation Information
doi:10.7908/C1D798TP
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between RPPA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1D798TP
Overview
Introduction

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

Summary

Testing the association between 175 genes and 15 clinical features across 211 samples, statistically thresholded by Q value < 0.05, 11 clinical features related to at least one genes.

- 1 gene correlated to 'Time to Death'.

- CHEK1|CHK1_PS345-R-C

- 16 genes correlated to 'AGE'.

- EEF2|EEF2-R-V , EGFR|EGFR_PY1068-R-V , SNAI2|SNAIL-M-C , MAPK8|JNK_PT183_PT185-R-V , RAD50|RAD50-M-C , ...

- 5 genes correlated to 'NEOPLASM.DISEASESTAGE'.

- BECN1|BECLIN-G-V , PECAM1|CD31-M-V , CASP3|CASPASE-3_ACTIVE-R-C , CDC2|CDK1-R-V , MAPT|TAU-M-C

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

- AKT1S1|PRAS40_PT246-R-V , DIABLO|SMAC-M-V

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

- ANXA1|ANNEXIN_I-R-V , SRC|SRC_PY527-R-V , DVL3|DVL3-R-V , PTCH1|PTCH-R-C , PXN|PAXILLIN-R-V , ...

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

- BCL2L1|BCL-XL-R-V

- 27 genes correlated to 'HISTOLOGICAL.TYPE'.

- ANXA1|ANNEXIN_I-R-V , FN1|FIBRONECTIN-R-C , PIK3R1|PI3K-P85-R-V , NEK7|NEK7-R-NA , CHEK2|CHK2-M-C , ...

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

- ERBB2|HER2_PY1248-R-V , MET|C-MET-M-C , DVL3|DVL3-R-V , WWTR1|TAZ_PS89-R-C , ARID1A|ARID1A-M-V , ...

- 6 genes correlated to 'EXTRATHYROIDAL.EXTENSION'.

- EIF4EBP1|4E-BP1-R-V , PIK3CA |PI3K-P110-ALPHA-R-C , EGFR|EGFR_PY1173-R-C , BCL2|BCL-2-R-C , PAI-1|PAL-1-M-C , ...

- 1 gene correlated to 'COMPLETENESS.OF.RESECTION'.

- LCK|LCK-R-V

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

- PTCH1|PTCH-R-C , DVL3|DVL3-R-V , MAPK14|P38_MAPK-R-C , ANXA1|ANNEXIN_I-R-V , PXN|PAXILLIN-R-V , ...

- No genes correlated to 'GENDER', 'RADIATIONEXPOSURE', 'MULTIFOCALITY', and 'TUMOR.SIZE'.

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=1 | shorter survival | N=0 | longer survival | N=1
AGE | Spearman correlation test | N=16 | older | N=9 | younger | N=7
NEOPLASM DISEASESTAGE | ANOVA test | N=5 |  |  |  |
PATHOLOGY T STAGE | Spearman correlation test | N=2 | higher stage | N=1 | lower stage | N=1
PATHOLOGY N STAGE | t test | N=16 | class1 | N=12 | class0 | N=4
PATHOLOGY M STAGE | ANOVA test | N=1 |  |  |  |
GENDER | t test | N=0 |  |  |  |
HISTOLOGICAL TYPE | ANOVA test | N=27 |  |  |  |
RADIATIONS RADIATION REGIMENINDICATION | t test | N=6 | yes | N=5 | no | N=1
RADIATIONEXPOSURE | t test | N=0 |  |  |  |
EXTRATHYROIDAL EXTENSION | ANOVA test | N=6 |  |  |  |
COMPLETENESS OF RESECTION | ANOVA test | N=1 |  |  |  |
NUMBER OF LYMPH NODES | Spearman correlation test | N=7 | higher number.of.lymph.nodes | N=6 | lower number.of.lymph.nodes | N=1
MULTIFOCALITY | t test | N=0 |  |  |  |
TUMOR SIZE | Spearman correlation test | N=0 |  |  |  |

Clinical variable #1: 'Time to Death'

One gene related to 'Time to Death'.

Table S1. Basic characteristics of clinical feature: 'Time to Death'

Time to Death | Duration (Months) | 0.1-158.8 (median=17.5)
| censored | N = 198
| death | N = 12
| Significant markers | N = 1
| associated with shorter survival | 0
| associated with longer survival | 1

List of one gene significantly associated with 'Time to Death' by Cox regression test

Table S2. Get Full Table List of one gene significantly associated with 'Time to Death' by Cox regression test

| HazardRatio | Wald_P | Q | C_index
--- | --- | --- | --- | ---
CHEK1|CHK1_PS345-R-C | 0 | 0.0001095 | 0.019 | 0.202

Figure S1. Get High-res Image As an example, this figure shows the association of CHEK1|CHK1_PS345-R-C to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 0.00011 with univariate Cox regression analysis using continuous log-2 expression values.

Clinical variable #2: 'AGE'

16 genes related to 'AGE'.

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

AGE | Mean (SD) | 48.06 (17)
| Significant markers | N = 16
| pos. correlated | 9
| neg. correlated | 7

List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

Table S4. Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
EEF2|EEF2-R-V | -0.3185 | 2.334e-06 | 0.000408
EGFR|EGFR_PY1068-R-V | 0.3089 | 4.811e-06 | 0.000837
SNAI2|SNAIL-M-C | 0.306 | 5.979e-06 | 0.00103
MAPK8|JNK_PT183_PT185-R-V | 0.2975 | 1.106e-05 | 0.0019
RAD50|RAD50-M-C | -0.293 | 1.513e-05 | 0.00259
ATM|ATM-R-C | -0.2862 | 2.437e-05 | 0.00414
DVL3|DVL3-R-V | -0.2842 | 2.778e-05 | 0.00469
AKT1 AKT2 AKT3|AKT_PT308-R-V | 0.28 | 3.687e-05 | 0.00619
XIAP|XIAP-R-C | -0.2767 | 4.594e-05 | 0.00767
XRCC5|KU80-R-C | -0.2717 | 6.374e-05 | 0.0106

Figure S2. Get High-res Image As an example, this figure shows the association of EEF2|EEF2-R-V to 'AGE'. P value = 2.33e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

5 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S5. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE | Labels | N
| STAGE I | 111
| STAGE II | 32
| STAGE III | 45
| STAGE IVA | 18
| STAGE IVC | 3
| Significant markers | N = 5

List of 5 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S6. Get Full Table List of 5 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

| ANOVA_P | Q
--- | --- | ---
BECN1|BECLIN-G-V | 2.497e-07 | 4.37e-05
PECAM1|CD31-M-V | 2.961e-05 | 0.00515
CASP3|CASPASE-3_ACTIVE-R-C | 5.834e-05 | 0.0101
CDC2|CDK1-R-V | 9.189e-05 | 0.0158
MAPT|TAU-M-C | 0.0002863 | 0.049

Figure S3. Get High-res Image As an example, this figure shows the association of BECN1|BECLIN-G-V to 'NEOPLASM.DISEASESTAGE'. P value = 2.5e-07 with ANOVA analysis.

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

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

Table S7. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE | Mean (SD) | 2.19 (0.85)
|  | N
| 1 | 50
| 2 | 80
| 3 | 71
| 4 | 9
| Significant markers | N = 2
| pos. correlated | 1
| neg. correlated | 1

List of 2 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

Table S8. Get Full Table List of 2 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
AKT1S1|PRAS40_PT246-R-V | -0.3196 | 2.266e-06 | 0.000396
DIABLO|SMAC-M-V | 0.2525 | 0.0002177 | 0.0379

Figure S4. Get High-res Image As an example, this figure shows the association of AKT1S1|PRAS40_PT246-R-V to 'PATHOLOGY.T.STAGE'. P value = 2.27e-06 with Spearman correlation analysis.

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

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

Table S9. Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE | Labels | N
| class0 | 92
| class1 | 90
| Significant markers | N = 16
| Higher in class1 | 12
| Higher in class0 | 4

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

Table S10. Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'

| T(pos if higher in 'class1') | ttestP | Q | AUC
--- | --- | --- | --- | ---
ANXA1|ANNEXIN_I-R-V | 5.93 | 1.831e-08 | 3.2e-06 | 0.719
SRC|SRC_PY527-R-V | -5.15 | 7.151e-07 | 0.000124 | 0.6976
DVL3|DVL3-R-V | 5.09 | 9.151e-07 | 0.000158 | 0.6999
PTCH1|PTCH-R-C | 4.71 | 5.032e-06 | 0.000865 | 0.7035
PXN|PAXILLIN-R-V | 4.62 | 7.272e-06 | 0.00124 | 0.6742
BCL2L1|BCL-XL-R-V | 4.45 | 1.518e-05 | 0.00258 | 0.6671
VASP|VASP-R-C | 4.44 | 1.625e-05 | 0.00275 | 0.6889
CASP9|CASPASE-9_CLEAVEDD330-R-C | 4.26 | 3.399e-05 | 0.00571 | 0.6713
ERBB2|HER2_PY1248-R-V | -3.9 | 0.0001353 | 0.0226 | 0.6826
FN1|FIBRONECTIN-R-C | 3.84 | 0.0001707 | 0.0283 | 0.6645

Figure S5. Get High-res Image As an example, this figure shows the association of ANXA1|ANNEXIN_I-R-V to 'PATHOLOGY.N.STAGE'. P value = 1.83e-08 with T-test analysis.

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

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

Table S11. Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE | Labels | N
| M0 | 109
| M1 | 4
| MX | 97
| Significant markers | N = 1

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

Table S12. Get Full Table List of one gene differentially expressed by 'PATHOLOGY.M.STAGE'

| ANOVA_P | Q
--- | --- | ---
BCL2L1|BCL-XL-R-V | 0.0002284 | 0.04

Figure S6. Get High-res Image As an example, this figure shows the association of BCL2L1|BCL-XL-R-V to 'PATHOLOGY.M.STAGE'. P value = 0.000228 with ANOVA analysis.

Clinical variable #7: 'GENDER'

No gene related to 'GENDER'.

Table S13. Basic characteristics of clinical feature: 'GENDER'

GENDER | Labels | N
| FEMALE | 147
| MALE | 64
| Significant markers | N = 0

Clinical variable #8: 'HISTOLOGICAL.TYPE'

27 genes related to 'HISTOLOGICAL.TYPE'.

Table S14. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE | Labels | N
| OTHER SPECIFY | 2
| THYROID PAPILLARY CARCINOMA - CLASSICAL/USUAL | 147
| THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED) | 52
| THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES) | 10
| Significant markers | N = 27

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

Table S15. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

| ANOVA_P | Q
--- | --- | ---
ANXA1|ANNEXIN_I-R-V | 1.856e-14 | 3.25e-12
FN1|FIBRONECTIN-R-C | 3.567e-11 | 6.21e-09
PIK3R1|PI3K-P85-R-V | 1.223e-08 | 2.12e-06
NEK7|NEK7-R-NA | 1.507e-07 | 2.59e-05
CHEK2|CHK2-M-C | 2.181e-07 | 3.73e-05
PXN|PAXILLIN-R-V | 6.749e-07 | 0.000115
STAT5A|STAT5-ALPHA-R-V | 1.22e-06 | 0.000206
RAF1|C-RAF_PS338-R-C | 1.594e-06 | 0.000268
XIAP|XIAP-R-C | 2.355e-06 | 0.000393
IGF1R|IGF-1R-BETA-R-C | 5.006e-06 | 0.000831

Figure S7. Get High-res Image As an example, this figure shows the association of ANXA1|ANNEXIN_I-R-V to 'HISTOLOGICAL.TYPE'. P value = 1.86e-14 with ANOVA analysis.

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

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

Table S16. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N
| NO | 13
| YES | 198
| Significant markers | N = 6
| Higher in YES | 5
| Higher in NO | 1

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

Table S17. Get Full Table List of 6 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

| T(pos if higher in 'YES') | ttestP | Q | AUC
--- | --- | --- | --- | ---
ERBB2|HER2_PY1248-R-V | 5 | 3.817e-05 | 0.00668 | 0.723
MET|C-MET-M-C | 4.91 | 5.021e-05 | 0.00874 | 0.6993
DVL3|DVL3-R-V | -5.29 | 5.833e-05 | 0.0101 | 0.799
WWTR1|TAZ_PS89-R-C | 5.08 | 9.47e-05 | 0.0163 | 0.791
ARID1A|ARID1A-M-V | 4.68 | 1e-04 | 0.0171 | 0.7012
IRS1|IRS1-R-V | 4.43 | 0.0002677 | 0.0455 | 0.7012

Figure S8. Get High-res Image As an example, this figure shows the association of ERBB2|HER2_PY1248-R-V to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 3.82e-05 with T-test analysis.

Clinical variable #10: 'RADIATIONEXPOSURE'

No gene related to 'RADIATIONEXPOSURE'.

Table S18. Basic characteristics of clinical feature: 'RADIATIONEXPOSURE'

RADIATIONEXPOSURE | Labels | N
| NO | 176
| YES | 11
| Significant markers | N = 0

Clinical variable #11: 'EXTRATHYROIDAL.EXTENSION'

6 genes related to 'EXTRATHYROIDAL.EXTENSION'.

Table S19. Basic characteristics of clinical feature: 'EXTRATHYROIDAL.EXTENSION'

EXTRATHYROIDAL.EXTENSION | Labels | N
| MINIMAL (T3) | 53
| MODERATE/ADVANCED (T4A) | 9
| NONE | 143
| Significant markers | N = 6

List of 6 genes differentially expressed by 'EXTRATHYROIDAL.EXTENSION'

Table S20. Get Full Table List of 6 genes differentially expressed by 'EXTRATHYROIDAL.EXTENSION'

| ANOVA_P | Q
--- | --- | ---
EIF4EBP1|4E-BP1-R-V | 5.508e-06 | 0.000964
PIK3CA |PI3K-P110-ALPHA-R-C | 6.935e-05 | 0.0121
EGFR|EGFR_PY1173-R-C | 7.823e-05 | 0.0135
BCL2|BCL-2-R-C | 9.076e-05 | 0.0156
PAI-1|PAL-1-M-C | 0.0001077 | 0.0184
DIABLO|SMAC-M-V | 0.0002292 | 0.039

Figure S9. Get High-res Image As an example, this figure shows the association of EIF4EBP1|4E-BP1-R-V to 'EXTRATHYROIDAL.EXTENSION'. P value = 5.51e-06 with ANOVA analysis.

Clinical variable #12: 'COMPLETENESS.OF.RESECTION'

One gene related to 'COMPLETENESS.OF.RESECTION'.

Table S21. Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION | Labels | N
| R0 | 163
| R1 | 20
| R2 | 1
| RX | 13
| Significant markers | N = 1

List of one gene differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S22. Get Full Table List of one gene differentially expressed by 'COMPLETENESS.OF.RESECTION'

| ANOVA_P | Q
--- | --- | ---
LCK|LCK-R-V | 4.897e-05 | 0.00857

Figure S10. Get High-res Image As an example, this figure shows the association of LCK|LCK-R-V to 'COMPLETENESS.OF.RESECTION'. P value = 4.9e-05 with ANOVA analysis.

Clinical variable #13: 'NUMBER.OF.LYMPH.NODES'

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

Table S23. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES | Mean (SD) | 3.42 (5.9)
| Significant markers | N = 7
| pos. correlated | 6
| neg. correlated | 1

List of 7 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

Table S24. Get Full Table List of 7 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
PTCH1|PTCH-R-C | 0.358 | 2.525e-06 | 0.000442
DVL3|DVL3-R-V | 0.3335 | 1.282e-05 | 0.00223
MAPK14|P38_MAPK-R-C | 0.325 | 2.171e-05 | 0.00376
ANXA1|ANNEXIN_I-R-V | 0.3154 | 3.886e-05 | 0.00668
PXN|PAXILLIN-R-V | 0.2961 | 0.0001186 | 0.0203
SRC|SRC_PY527-R-V | -0.2904 | 0.0001616 | 0.0275
VASP|VASP-R-C | 0.2806 | 0.0002738 | 0.0463

Figure S11. Get High-res Image As an example, this figure shows the association of PTCH1|PTCH-R-C to 'NUMBER.OF.LYMPH.NODES'. P value = 2.53e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #14: 'MULTIFOCALITY'

No gene related to 'MULTIFOCALITY'.

Table S25. Basic characteristics of clinical feature: 'MULTIFOCALITY'

MULTIFOCALITY | Labels | N
| MULTIFOCAL | 97
| UNIFOCAL | 107
| Significant markers | N = 0

Clinical variable #15: 'TUMOR.SIZE'

No gene related to 'TUMOR.SIZE'.

Table S26. Basic characteristics of clinical feature: 'TUMOR.SIZE'

TUMOR.SIZE | Mean (SD) | 3.26 (1.6)
| Significant markers | N = 0

Methods & Data
Input

- Expresson data file = THCA-TP.rppa.txt

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

- Number of patients = 211

- Number of genes = 175

- Number of clinical features = 15

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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