Correlation between RPPA expression and clinical features
Thyroid Adenocarcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1G44P85
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between RPPA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1G44P85
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 17 clinical features across 222 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 12 clinical features related to at least one genes.

  • 2 genes correlated to 'Time to Death'.

    • CHEK1|CHK1_PS345-R-C ,  COL6A1|COLLAGEN_VI-R-V

  • 23 genes correlated to 'AGE'.

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

  • 13 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • CDK1|CDK1-R-V ,  MAPK8|JNK_PT183_PT185-R-V ,  CASP3|CASPASE-3_ACTIVE-R-C ,  PECAM1|CD31-M-V ,  RAF1|C-RAF-R-V ,  ...

  • 8 genes correlated to 'PATHOLOGY.T.STAGE'.

    • AKT1S1|PRAS40_PT246-R-V ,  DIABLO|SMAC-M-V ,  CLDN7|CLAUDIN-7-R-V ,  AR|AR-R-V ,  C12ORF5|TIGAR-R-V ,  ...

  • 34 genes correlated to 'PATHOLOGY.N.STAGE'.

    • ANXA1|ANNEXIN_I-R-V ,  PTCH1|PTCH-R-C ,  SRC|SRC_PY527-R-V ,  DVL3|DVL3-R-V ,  RAF1|C-RAF_PS338-R-C ,  ...

  • 4 genes correlated to 'PATHOLOGY.M.STAGE'.

    • BCL2L1|BCL-XL-R-V ,  BAK1|BAK-R-C ,  ESR1|ER-ALPHA_PS118-R-V ,  DVL3|DVL3-R-V

  • 49 genes correlated to 'HISTOLOGICAL.TYPE'.

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

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

    • BCL2L1|BCL-XL-R-V ,  DVL3|DVL3-R-V ,  WWTR1|TAZ_PS89-R-C ,  RAF1|C-RAF-R-V ,  C12ORF5|TIGAR-R-V ,  ...

  • 13 genes correlated to 'EXTRATHYROIDAL.EXTENSION'.

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

  • 12 genes correlated to 'NUMBER.OF.LYMPH.NODES'.

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

  • 1 gene correlated to 'MULTIFOCALITY'.

    • CDKN1B|P27_PT157-R-C

  • 2 genes correlated to 'RACE'.

    • FOXO3|FOXO3A_PS318_S321-R-C ,  |P-REX1-R-NA

  • No genes correlated to 'GENDER', 'RADIATIONEXPOSURE', 'COMPLETENESS.OF.RESECTION', 'TUMOR.SIZE', and 'ETHNICITY'.

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 P value < 0.05 and Q value < 0.3.

Clinical feature Statistical test Significant genes Associated with                 Associated with
Time to Death Cox regression test N=2 shorter survival N=1 longer survival N=1
AGE Spearman correlation test N=23 older N=13 younger N=10
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=13        
PATHOLOGY T STAGE Spearman correlation test N=8 higher stage N=3 lower stage N=5
PATHOLOGY N STAGE Wilcoxon test N=34 class1 N=34 class0 N=0
PATHOLOGY M STAGE Kruskal-Wallis test N=4        
GENDER Wilcoxon test   N=0        
HISTOLOGICAL TYPE Kruskal-Wallis test N=49        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test N=6 yes N=6 no N=0
RADIATIONEXPOSURE Wilcoxon test   N=0        
EXTRATHYROIDAL EXTENSION Kruskal-Wallis test N=13        
COMPLETENESS OF RESECTION Kruskal-Wallis test   N=0        
NUMBER OF LYMPH NODES Spearman correlation test N=12 higher number.of.lymph.nodes N=10 lower number.of.lymph.nodes N=2
MULTIFOCALITY Wilcoxon test N=1 unifocal N=1 multifocal N=0
TUMOR SIZE Spearman correlation test   N=0        
RACE Kruskal-Wallis test N=2        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'Time to Death'

2 genes 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=17.6)
  censored N = 208
  death N = 13
     
  Significant markers N = 2
  associated with shorter survival 1
  associated with longer survival 1
List of 2 genes differentially expressed by 'Time to Death'

Table S2.  Get Full Table List of 2 genes significantly associated with 'Time to Death' by Cox regression test

HazardRatio Wald_P Q C_index
CHEK1|CHK1_PS345-R-C 0 9.717e-05 0.017 0.203
COL6A1|COLLAGEN_VI-R-V 2.4 0.001471 0.26 0.664
Clinical variable #2: 'AGE'

23 genes related to 'AGE'.

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

AGE Mean (SD) 48.09 (17)
  Significant markers N = 23
  pos. correlated 13
  neg. correlated 10
List of top 10 genes differentially expressed by 'AGE'

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

SpearmanCorr corrP Q
EGFR|EGFR_PY1068-R-V 0.3013 4.848e-06 0.000848
SNAI2|SNAIL-M-C 0.2959 7.318e-06 0.00127
EEF2|EEF2-R-V -0.2859 1.514e-05 0.00262
ATM|ATM-R-C -0.2803 2.248e-05 0.00387
MAPK8|JNK_PT183_PT185-R-V 0.2749 3.27e-05 0.00559
AKT1 AKT2 AKT3|AKT_PT308-R-V 0.2614 8.079e-05 0.0137
AKT1 AKT2 AKT3|AKT_PS473-R-V 0.2567 0.0001094 0.0185
DVL3|DVL3-R-V -0.25 0.0001677 0.0282
RAD50|RAD50-M-C -0.2488 0.0001798 0.03
PRKCA |PKC-ALPHA-M-V 0.2422 0.0002695 0.0447
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

13 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 117
  STAGE II 33
  STAGE III 45
  STAGE IVA 21
  STAGE IVC 4
     
  Significant markers N = 13
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

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

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

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

PATHOLOGY.T.STAGE Mean (SD) 2.2 (0.86)
  N
  1 52
  2 83
  3 74
  4 11
     
  Significant markers N = 8
  pos. correlated 3
  neg. correlated 5
List of 8 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S8.  Get Full Table List of 8 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
AKT1S1|PRAS40_PT246-R-V -0.3166 1.645e-06 0.000288
DIABLO|SMAC-M-V 0.257 0.0001155 0.0201
CLDN7|CLAUDIN-7-R-V -0.2501 0.0001777 0.0307
AR|AR-R-V -0.2467 0.0002192 0.0377
C12ORF5|TIGAR-R-V -0.2362 0.000411 0.0703
COL6A1|COLLAGEN_VI-R-V -0.2255 0.0007543 0.128
PIK3CA |PI3K-P110-ALPHA-R-C 0.2247 0.0007885 0.133
EEF2|EEF2-R-V 0.2102 0.001719 0.289
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

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

PATHOLOGY.N.STAGE Labels N
  class0 98
  class1 95
     
  Significant markers N = 34
  Higher in class1 34
  Higher in class0 0
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'

W(pos if higher in 'class1') wilcoxontestP Q AUC
ANXA1|ANNEXIN_I-R-V 6777 4.542e-08 7.95e-06 0.7279
PTCH1|PTCH-R-C 6672 2.017e-07 3.51e-05 0.7166
SRC|SRC_PY527-R-V 2729 6.935e-07 0.00012 0.7069
DVL3|DVL3-R-V 6555.5 9.71e-07 0.000167 0.7041
RAF1|C-RAF_PS338-R-C 2928 8.578e-06 0.00147 0.6855
ERBB2|HER2_PY1248-R-V 2928 8.578e-06 0.00147 0.6855
EEF2|EEF2-R-V 6346.5 1.308e-05 0.00221 0.6817
VASP|VASP-R-C 6339 1.429e-05 0.0024 0.6809
FN1|FIBRONECTIN-R-C 6299 2.273e-05 0.0038 0.6766
PXN|PAXILLIN-R-V 6267 3.27e-05 0.00543 0.6731
Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

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

PATHOLOGY.M.STAGE Labels N
  M0 118
  M1 5
  MX 98
     
  Significant markers N = 4
List of 4 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S12.  Get Full Table List of 4 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
BCL2L1|BCL-XL-R-V 0.0001008 0.0176
BAK1|BAK-R-C 0.0007615 0.133
ESR1|ER-ALPHA_PS118-R-V 0.001083 0.187
DVL3|DVL3-R-V 0.001306 0.225
Clinical variable #7: 'GENDER'

No gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 154
  MALE 68
     
  Significant markers N = 0
Clinical variable #8: 'HISTOLOGICAL.TYPE'

49 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 158
  THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED) 52
  THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES) 10
     
  Significant markers N = 49
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 2.162e-10 3.78e-08
FN1|FIBRONECTIN-R-C 1.139e-09 1.98e-07
PIK3R1|PI3K-P85-R-V 1.703e-09 2.95e-07
CHEK2|CHK2-M-C 1.443e-07 2.48e-05
XIAP|XIAP-R-C 2.429e-07 4.15e-05
NEK7|NEK7-R-NA 2.894e-07 4.92e-05
ERCC1|ERCC1-M-C 7.334e-07 0.000124
PXN|PAXILLIN-R-V 8.551e-07 0.000144
RAF1|C-RAF_PS338-R-C 1.306e-06 0.000218
COL6A1|COLLAGEN_VI-R-V 3.725e-06 0.000618
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 209
     
  Significant markers N = 6
  Higher in YES 6
  Higher in NO 0
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'

W(pos if higher in 'YES') wilcoxontestP Q AUC
BCL2L1|BCL-XL-R-V 453 5.636e-05 0.00986 0.8333
DVL3|DVL3-R-V 533.5 0.0002432 0.0423 0.8036
WWTR1|TAZ_PS89-R-C 2143 0.0004847 0.0839 0.7887
RAF1|C-RAF-R-V 2136 0.0005444 0.0936 0.7862
C12ORF5|TIGAR-R-V 2135 0.0005534 0.0946 0.7858
XRCC1|XRCC1-R-C 612 0.0009003 0.153 0.7748
Clinical variable #10: 'RADIATIONEXPOSURE'

No gene related to 'RADIATIONEXPOSURE'.

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

RADIATIONEXPOSURE Labels N
  NO 184
  YES 11
     
  Significant markers N = 0
Clinical variable #11: 'EXTRATHYROIDAL.EXTENSION'

13 genes related to 'EXTRATHYROIDAL.EXTENSION'.

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

EXTRATHYROIDAL.EXTENSION Labels N
  MINIMAL (T3) 55
  MODERATE/ADVANCED (T4A) 10
  NONE 149
     
  Significant markers N = 13
List of top 10 genes differentially expressed by 'EXTRATHYROIDAL.EXTENSION'

Table S20.  Get Full Table List of top 10 genes differentially expressed by 'EXTRATHYROIDAL.EXTENSION'

ANOVA_P Q
PIK3CA |PI3K-P110-ALPHA-R-C 2.353e-05 0.00412
EIF4EBP1|4E-BP1-R-V 2.748e-05 0.00478
BCL2|BCL-2-R-C 5.105e-05 0.00883
EGFR|EGFR_PY1173-R-C 5.295e-05 0.00911
PAI-1|PAL-1-M-C 9.793e-05 0.0167
BECN1|BECLIN-G-V 0.0001491 0.0254
DIABLO|SMAC-M-V 0.0001829 0.0309
MAPT|TAU-M-C 0.0002035 0.0342
RAF1|C-RAF-R-V 0.001013 0.169
INPP4B|INPP4B-G-C 0.001154 0.192
Clinical variable #12: 'COMPLETENESS.OF.RESECTION'

No gene related to 'COMPLETENESS.OF.RESECTION'.

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

COMPLETENESS.OF.RESECTION Labels N
  R0 168
  R1 23
  R2 2
  RX 14
     
  Significant markers N = 0
Clinical variable #13: 'NUMBER.OF.LYMPH.NODES'

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

Table S22.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 3.44 (5.8)
  Significant markers N = 12
  pos. correlated 10
  neg. correlated 2
List of top 10 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S23.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
PTCH1|PTCH-R-C 0.3466 3.646e-06 0.000638
MAPK14|P38_MAPK-R-C 0.3298 1.126e-05 0.00196
ANXA1|ANNEXIN_I-R-V 0.3145 2.963e-05 0.00513
DVL3|DVL3-R-V 0.3121 3.432e-05 0.0059
PXN|PAXILLIN-R-V 0.2967 8.518e-05 0.0146
PAI-1|PAL-1-M-C 0.283 0.0001841 0.0313
PTGS2|COX-2-R-C 0.2783 0.0002384 0.0403
SRC|SRC_PY527-R-V -0.2742 0.000296 0.0497
VASP|VASP-R-C 0.2629 0.000532 0.0889
KIT|C-KIT-R-V -0.2564 0.0007364 0.122
Clinical variable #14: 'MULTIFOCALITY'

One gene related to 'MULTIFOCALITY'.

Table S24.  Basic characteristics of clinical feature: 'MULTIFOCALITY'

MULTIFOCALITY Labels N
  MULTIFOCAL 101
  UNIFOCAL 114
     
  Significant markers N = 1
  Higher in UNIFOCAL 1
  Higher in MULTIFOCAL 0
List of one gene differentially expressed by 'MULTIFOCALITY'

Table S25.  Get Full Table List of one gene differentially expressed by 'MULTIFOCALITY'

W(pos if higher in 'UNIFOCAL') wilcoxontestP Q AUC
CDKN1B|P27_PT157-R-C 4191 0.0005843 0.102 0.636
Clinical variable #15: 'TUMOR.SIZE'

No gene related to 'TUMOR.SIZE'.

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

TUMOR.SIZE Mean (SD) 3.29 (1.6)
  Significant markers N = 0
Clinical variable #16: 'RACE'

2 genes related to 'RACE'.

Table S27.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  ASIAN 13
  BLACK OR AFRICAN AMERICAN 13
  WHITE 145
     
  Significant markers N = 2
List of 2 genes differentially expressed by 'RACE'

Table S28.  Get Full Table List of 2 genes differentially expressed by 'RACE'

ANOVA_P Q
FOXO3|FOXO3A_PS318_S321-R-C 0.000581 0.102
|P-REX1-R-NA 0.0006055 0.105
Clinical variable #17: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S29.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 16
  NOT HISPANIC OR LATINO 164
     
  Significant markers N = 0
Methods & Data
Input

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

  • Clinical data file = THCA-TP.merged_data.txt

  • Number of patients = 222

  • Number of genes = 175

  • Number of clinical features = 17

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.

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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