Correlation between RPPA expression and clinical features
Colorectal Adenocarcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1BP01PF
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/C1BP01PF
Overview
Introduction

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

Summary

Testing the association between 171 genes and 13 clinical features across 461 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one genes.

  • 1 gene correlated to 'AGE'.

    • MAP2K1|MEK1_PS217_S221-R-V

  • 102 genes correlated to 'PRIMARY.SITE.OF.DISEASE'.

    • CHEK1|CHK1_PS345-R-C ,  ERBB3|HER3_PY1298-R-C ,  MRE11A|MRE11-R-C ,  EGFR|EGFR-R-C ,  STK11|LKB1-M-NA ,  ...

  • 9 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • CASP7|CASPASE-7_CLEAVEDD198-R-C ,  PIK3CA|PI3K-P110-ALPHA-R-C ,  PTK2|FAK-R-C ,  YAP1|YAP-R-V ,  NOTCH3|NOTCH3-R-C ,  ...

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

    • PTGS2|COX-2-R-C ,  ERRFI1|MIG-6-M-V ,  NOTCH3|NOTCH3-R-C ,  RB1|RB_PS807_S811-R-V ,  SRC|SRC_PY527-R-V ,  ...

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

    • EIF4E|EIF4E-R-V ,  IRS1|IRS1-R-V ,  CASP7|CASPASE-7_CLEAVEDD198-R-C ,  PXN|PAXILLIN-R-V ,  BAX|BAX-R-V ,  ...

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

    • CASP7|CASPASE-7_CLEAVEDD198-R-C ,  YBX1|YB-1-R-V

  • 101 genes correlated to 'HISTOLOGICAL.TYPE'.

    • ERBB3|HER3_PY1298-R-C ,  MRE11A|MRE11-R-C ,  CHEK1|CHK1_PS345-R-C ,  STK11|LKB1-M-NA ,  EGFR|EGFR_PY1173-R-C ,  ...

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

    • EIF4EBP1|4E-BP1_PT37-R-V ,  PECAM1|CD31-M-V

  • 3 genes correlated to 'COMPLETENESS.OF.RESECTION'.

    • BID|BID-R-C ,  BCL2|BCL-2-R-NA ,  PIK3CA|PI3K-P110-ALPHA-R-C

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

    • IRS1|IRS1-R-V ,  EIF4E|EIF4E-R-V ,  GAB2|GAB2-R-V ,  PXN|PAXILLIN-R-V ,  CASP7|CASPASE-7_CLEAVEDD198-R-C ,  ...

  • No genes correlated to 'Time to Death', 'GENDER', and 'RACE'.

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=0        
AGE Spearman correlation test N=1 older N=1 younger N=0
PRIMARY SITE OF DISEASE Wilcoxon test N=102 rectum N=102 colon N=0
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=9        
PATHOLOGY T STAGE Spearman correlation test N=6 higher stage N=3 lower stage N=3
PATHOLOGY N STAGE Spearman correlation test N=14 higher stage N=6 lower stage N=8
PATHOLOGY M STAGE Kruskal-Wallis test N=2        
GENDER Wilcoxon test   N=0        
HISTOLOGICAL TYPE Kruskal-Wallis test N=101        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test N=2 yes N=2 no N=0
COMPLETENESS OF RESECTION Kruskal-Wallis test N=3        
NUMBER OF LYMPH NODES Spearman correlation test N=20 higher number.of.lymph.nodes N=9 lower number.of.lymph.nodes N=11
RACE Kruskal-Wallis 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) 0.1-140.4 (median=18.2)
  censored N = 352
  death N = 87
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

One gene related to 'AGE'.

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

AGE Mean (SD) 66.78 (13)
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene differentially expressed by 'AGE'

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

SpearmanCorr corrP Q
MAP2K1|MEK1_PS217_S221-R-V 0.1483 0.001423 0.243
Clinical variable #3: 'PRIMARY.SITE.OF.DISEASE'

102 genes related to 'PRIMARY.SITE.OF.DISEASE'.

Table S4.  Basic characteristics of clinical feature: 'PRIMARY.SITE.OF.DISEASE'

PRIMARY.SITE.OF.DISEASE Labels N
  COLON 331
  RECTUM 130
     
  Significant markers N = 102
  Higher in RECTUM 102
  Higher in COLON 0
List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

Table S5.  Get Full Table List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

W(pos if higher in 'RECTUM') wilcoxontestP Q AUC
CHEK1|CHK1_PS345-R-C 9458 7.455e-21 1.27e-18 0.7802
ERBB3|HER3_PY1298-R-C 9521 1.184e-20 2.01e-18 0.7787
MRE11A|MRE11-R-C 10092 7.023e-19 1.19e-16 0.7655
EGFR|EGFR-R-C 10373 4.877e-18 8.19e-16 0.7589
STK11|LKB1-M-NA 10544 1.55e-17 2.59e-15 0.755
BECN1|BECLIN-G-V 10707 4.592e-17 7.62e-15 0.7512
EGFR|EGFR_PY1173-R-C 10816 9.407e-17 1.55e-14 0.7486
PIK3R1|PI3K-P85-R-V 11006 3.23e-16 5.3e-14 0.7442
BIRC2|CIAP-R-V 11097 5.787e-16 9.43e-14 0.7421
CDKN1B|P27_PT157-R-C 11242 1.451e-15 2.35e-13 0.7387
Clinical variable #4: 'NEOPLASM.DISEASESTAGE'

9 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S6.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 70
  STAGE IA 1
  STAGE II 27
  STAGE IIA 139
  STAGE IIB 9
  STAGE IIC 2
  STAGE III 24
  STAGE IIIA 16
  STAGE IIIB 62
  STAGE IIIC 39
  STAGE IV 44
  STAGE IVA 19
  STAGE IVB 1
     
  Significant markers N = 9
List of 9 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S7.  Get Full Table List of 9 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
CASP7|CASPASE-7_CLEAVEDD198-R-C 1.692e-06 0.000289
PIK3CA|PI3K-P110-ALPHA-R-C 2.302e-05 0.00391
PTK2|FAK-R-C 5.24e-05 0.00886
YAP1|YAP-R-V 0.0001385 0.0233
NOTCH3|NOTCH3-R-C 0.0001996 0.0333
PXN|PAXILLIN-R-V 0.0003891 0.0646
RB1|RB_PS807_S811-R-V 0.0009618 0.159
BAK1|BAK-R-C 0.0009766 0.16
ERRFI1|MIG-6-M-V 0.001004 0.164
Clinical variable #5: 'PATHOLOGY.T.STAGE'

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

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.89 (0.6)
  N
  1 11
  2 76
  3 324
  4 48
     
  Significant markers N = 6
  pos. correlated 3
  neg. correlated 3
List of 6 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S9.  Get Full Table List of 6 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
PTGS2|COX-2-R-C 0.1759 0.0001526 0.0261
ERRFI1|MIG-6-M-V 0.1681 0.0002985 0.0507
NOTCH3|NOTCH3-R-C 0.1625 0.0004755 0.0804
RB1|RB_PS807_S811-R-V -0.1518 0.001104 0.186
SRC|SRC_PY527-R-V -0.1491 0.001357 0.227
SRC|SRC_PY416-R-C -0.1474 0.00154 0.256
Clinical variable #6: 'PATHOLOGY.N.STAGE'

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

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

PATHOLOGY.N.STAGE Mean (SD) 0.61 (0.77)
  N
  0 260
  1 117
  2 81
     
  Significant markers N = 14
  pos. correlated 6
  neg. correlated 8
List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S11.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
EIF4E|EIF4E-R-V -0.1987 1.844e-05 0.00315
IRS1|IRS1-R-V 0.1959 2.428e-05 0.00413
CASP7|CASPASE-7_CLEAVEDD198-R-C -0.1921 3.5e-05 0.00591
PXN|PAXILLIN-R-V 0.1773 0.0001371 0.023
BAX|BAX-R-V -0.1742 0.0001786 0.0298
MYC|C-MYC-R-C 0.1739 0.0001833 0.0304
BCL2|BCL-2-R-NA -0.1666 0.000342 0.0564
CCNE1|CYCLIN_E1-M-V -0.1656 0.000373 0.0612
GAB2|GAB2-R-V 0.1631 0.0004558 0.0743
MAPK14|P38_MAPK-R-C -0.1581 0.0006851 0.111
Clinical variable #7: 'PATHOLOGY.M.STAGE'

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

Table S12.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 357
  M1 54
  M1A 8
  M1B 1
  MX 36
     
  Significant markers N = 2
List of 2 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S13.  Get Full Table List of 2 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
CASP7|CASPASE-7_CLEAVEDD198-R-C 0.000242 0.0414
YBX1|YB-1-R-V 0.001475 0.251
Clinical variable #8: 'GENDER'

No gene related to 'GENDER'.

Table S14.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 215
  MALE 246
     
  Significant markers N = 0
Clinical variable #9: 'HISTOLOGICAL.TYPE'

101 genes related to 'HISTOLOGICAL.TYPE'.

Table S15.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  COLON ADENOCARCINOMA 293
  COLON MUCINOUS ADENOCARCINOMA 38
  RECTAL ADENOCARCINOMA 117
  RECTAL MUCINOUS ADENOCARCINOMA 10
     
  Significant markers N = 101
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S16.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
ERBB3|HER3_PY1298-R-C 1.158e-20 1.98e-18
MRE11A|MRE11-R-C 2.855e-19 4.85e-17
CHEK1|CHK1_PS345-R-C 1.017e-18 1.72e-16
STK11|LKB1-M-NA 1.927e-16 3.24e-14
EGFR|EGFR_PY1173-R-C 1.207e-15 2.02e-13
EGFR|EGFR-R-C 1.594e-15 2.65e-13
BECN1|BECLIN-G-V 3.227e-15 5.32e-13
MET|C-MET_PY1235-R-C 3.416e-15 5.6e-13
PIK3R1|PI3K-P85-R-V 1.919e-14 3.13e-12
XIAP|XIAP-R-C 1.976e-14 3.2e-12
Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S17.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 8
  YES 453
     
  Significant markers N = 2
  Higher in YES 2
  Higher in NO 0
List of 2 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S18.  Get Full Table List of 2 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

W(pos if higher in 'YES') wilcoxontestP Q AUC
EIF4EBP1|4E-BP1_PT37-R-V 3035 0.001065 0.182 0.8375
PECAM1|CD31-M-V 595 0.001127 0.192 0.8358
Clinical variable #11: 'COMPLETENESS.OF.RESECTION'

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

Table S19.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 338
  R1 2
  R2 28
  RX 19
     
  Significant markers N = 3
List of 3 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S20.  Get Full Table List of 3 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
BID|BID-R-C 0.0002745 0.0469
BCL2|BCL-2-R-NA 0.0003925 0.0667
PIK3CA|PI3K-P110-ALPHA-R-C 0.0004175 0.0706
Clinical variable #12: 'NUMBER.OF.LYMPH.NODES'

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

Table S21.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.1 (4.6)
  Significant markers N = 20
  pos. correlated 9
  neg. correlated 11
List of top 10 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S22.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
IRS1|IRS1-R-V 0.2271 1.705e-06 0.000292
EIF4E|EIF4E-R-V -0.2081 1.212e-05 0.00206
GAB2|GAB2-R-V 0.2012 2.373e-05 0.00401
PXN|PAXILLIN-R-V 0.1963 3.737e-05 0.00628
CASP7|CASPASE-7_CLEAVEDD198-R-C -0.1931 5.035e-05 0.00841
BAX|BAX-R-V -0.183 0.0001243 0.0206
XRCC1|XRCC1-R-C -0.1801 0.0001587 0.0262
CCNE1|CYCLIN_E1-M-V -0.1611 0.0007443 0.122
MAPK14|P38_MAPK-R-C -0.1609 0.0007586 0.124
SRC|SRC_PY416-R-C -0.1578 0.0009571 0.155
Clinical variable #13: 'RACE'

No gene related to 'RACE'.

Table S23.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 12
  BLACK OR AFRICAN AMERICAN 24
  WHITE 246
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 461

  • Number of genes = 171

  • Number of clinical features = 13

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

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] 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)
Copyright © 2015 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle