Correlation between RPPA expression and clinical features
Colorectal Adenocarcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1KP815X
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Correlation between RPPA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1KP815X
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.

  • 11 genes correlated to 'YEARS_TO_BIRTH'.

    • MAP2K1|MEK1_PS217_S221-R-V ,  RB1|RB_PS807_S811-R-V ,  YAP1|YAP-R-V ,  SRC|SRC-M-V ,  ERBB2|HER2-M-V ,  ...

  • 30 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 ,  ...

  • 30 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 ,  ...

  • 30 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 ,  ...

  • 30 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 ,  ...

  • 30 genes correlated to 'PATHOLOGY_M_STAGE'.

    • CASP7|CASPASE-7_CLEAVEDD198-R-C ,  PTK2|FAK-R-C ,  MAPK14|P38_MAPK-R-C ,  CCNE1|CYCLIN_E1-M-V ,  NCOA3|AIB1-M-V ,  ...

  • 30 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 ,  ...

  • 3 genes correlated to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

    • EIF4EBP1|4E-BP1_PT37-R-V ,  PECAM1|CD31-M-V ,  EIF4EBP1|4E-BP1_PT70-R-C

  • 30 genes correlated to 'COMPLETENESS_OF_RESECTION'.

    • BID|BID-R-C ,  BCL2|BCL-2-R-NA ,  PIK3CA|PI3K-P110-ALPHA-R-C ,  PEA15|PEA-15-R-V ,  NCOA3|AIB1-M-V ,  ...

  • 30 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 'DAYS_TO_DEATH_OR_LAST_FUP', '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
DAYS_TO_DEATH_OR_LAST_FUP Cox regression test   N=0        
YEARS_TO_BIRTH Spearman correlation test N=11 older N=5 younger N=6
PRIMARY_SITE_OF_DISEASE Wilcoxon test N=30 rectum N=30 colon N=0
NEOPLASM_DISEASESTAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=18 lower stage N=12
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=12 lower stage N=18
PATHOLOGY_M_STAGE Wilcoxon test N=30 class1 N=30 class0 N=0
GENDER Wilcoxon test   N=0        
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
RADIATIONS_RADIATION_REGIMENINDICATION Wilcoxon test N=3 yes N=3 no N=0
COMPLETENESS_OF_RESECTION Kruskal-Wallis test N=30        
NUMBER_OF_LYMPH_NODES Spearman correlation test N=30 higher number_of_lymph_nodes N=11 lower number_of_lymph_nodes N=19
RACE Kruskal-Wallis test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

No gene related to 'DAYS_TO_DEATH_OR_LAST_FUP'.

Table S1.  Basic characteristics of clinical feature: 'DAYS_TO_DEATH_OR_LAST_FUP'

DAYS_TO_DEATH_OR_LAST_FUP Duration (Months) 0-140.4 (median=19.7)
  censored N = 370
  death N = 90
     
  Significant markers N = 0
Clinical variable #2: 'YEARS_TO_BIRTH'

11 genes related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 66.78 (13)
  Significant markers N = 11
  pos. correlated 5
  neg. correlated 6
List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

Table S3.  Get Full Table List of top 10 genes significantly correlated to 'YEARS_TO_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
MAP2K1|MEK1_PS217_S221-R-V 0.1483 0.001423 0.186
RB1|RB_PS807_S811-R-V 0.137 0.003247 0.186
YAP1|YAP-R-V -0.1336 0.004095 0.186
SRC|SRC-M-V -0.1327 0.004347 0.186
ERBB2|HER2-M-V 0.1278 0.006066 0.195
BID|BID-R-C -0.126 0.006833 0.195
ERBB2|HER2_PY1248-R-V 0.1201 0.009955 0.243
MAPT|TAU-M-C -0.1154 0.0133 0.271
CTNNA1|ALPHA-CATENIN-M-V -0.1142 0.01424 0.271
CASP7|CASPASE-7_CLEAVEDD198-R-C 0.1114 0.01681 0.288
Clinical variable #3: 'PRIMARY_SITE_OF_DISEASE'

30 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 = 30
  Higher in RECTUM 30
  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 1.01e-18 0.7802
ERBB3|HER3_PY1298-R-C 9521 1.184e-20 1.01e-18 0.7787
MRE11A|MRE11-R-C 10092 7.023e-19 4e-17 0.7655
EGFR|EGFR-R-C 10373 4.877e-18 2.08e-16 0.7589
STK11|LKB1-M-NA 10544 1.55e-17 5.3e-16 0.755
BECN1|BECLIN-G-V 10707 4.592e-17 1.31e-15 0.7512
EGFR|EGFR_PY1173-R-C 10816 9.407e-17 2.3e-15 0.7486
PIK3R1|PI3K-P85-R-V 11006 3.23e-16 6.9e-15 0.7442
BIRC2|CIAP-R-V 11097 5.787e-16 1.1e-14 0.7421
CDKN1B|P27_PT157-R-C 11242 1.451e-15 2.48e-14 0.7387
Clinical variable #4: 'NEOPLASM_DISEASESTAGE'

30 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 = 30
List of top 10 genes differentially expressed by 'NEOPLASM_DISEASESTAGE'

Table S7.  Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM_DISEASESTAGE'

kruskal_wallis_P Q
CASP7|CASPASE-7_CLEAVEDD198-R-C 1.692e-06 0.000289
PIK3CA|PI3K-P110-ALPHA-R-C 2.302e-05 0.00197
PTK2|FAK-R-C 5.24e-05 0.00299
YAP1|YAP-R-V 0.0001385 0.00592
NOTCH3|NOTCH3-R-C 0.0001996 0.00683
PXN|PAXILLIN-R-V 0.0003891 0.0111
RB1|RB_PS807_S811-R-V 0.0009618 0.0191
BAK1|BAK-R-C 0.0009766 0.0191
ERRFI1|MIG-6-M-V 0.001004 0.0191
BID|BID-R-C 0.002386 0.0408
Clinical variable #5: 'PATHOLOGY_T_STAGE'

30 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
  T1 11
  T2 76
  T3 324
  T4 48
     
  Significant markers N = 30
  pos. correlated 18
  neg. correlated 12
List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S9.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
PTGS2|COX-2-R-C 0.1759 0.0001526 0.0255
ERRFI1|MIG-6-M-V 0.1681 0.0002985 0.0255
NOTCH3|NOTCH3-R-C 0.1625 0.0004755 0.0271
RB1|RB_PS807_S811-R-V -0.1518 0.001104 0.0439
SRC|SRC_PY527-R-V -0.1491 0.001357 0.0439
SRC|SRC_PY416-R-C -0.1474 0.00154 0.0439
EIF4EBP1|4E-BP1_PT37-R-V -0.1442 0.001955 0.0478
RAB25|RAB25-R-C 0.141 0.002465 0.0527
WWTR1|TAZ-R-C 0.1362 0.003457 0.0593
EGFR|EGFR-R-C 0.1362 0.003466 0.0593
Clinical variable #6: 'PATHOLOGY_N_STAGE'

30 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
  N0 260
  N1 117
  N2 81
     
  Significant markers N = 30
  pos. correlated 12
  neg. correlated 18
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 0.00199
IRS1|IRS1-R-V 0.1959 2.428e-05 0.00199
CASP7|CASPASE-7_CLEAVEDD198-R-C -0.1921 3.5e-05 0.00199
PXN|PAXILLIN-R-V 0.1773 0.0001371 0.00522
BAX|BAX-R-V -0.1742 0.0001786 0.00522
MYC|C-MYC-R-C 0.1739 0.0001833 0.00522
BCL2|BCL-2-R-NA -0.1666 0.000342 0.00797
CCNE1|CYCLIN_E1-M-V -0.1656 0.000373 0.00797
GAB2|GAB2-R-V 0.1631 0.0004558 0.00866
MAPK14|P38_MAPK-R-C -0.1581 0.0006851 0.0117
Clinical variable #7: 'PATHOLOGY_M_STAGE'

30 genes related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 357
  class1 63
     
  Significant markers N = 30
  Higher in class1 30
  Higher in class0 0
List of top 10 genes differentially expressed by 'PATHOLOGY_M_STAGE'

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

W(pos if higher in 'class1') wilcoxontestP Q AUC
CASP7|CASPASE-7_CLEAVEDD198-R-C 7519 2.734e-05 0.00467 0.6657
PTK2|FAK-R-C 14241 0.0007472 0.0639 0.6332
MAPK14|P38_MAPK-R-C 8445 0.001621 0.0902 0.6245
CCNE1|CYCLIN_E1-M-V 8514 0.002109 0.0902 0.6214
NCOA3|AIB1-M-V 13833 0.003587 0.123 0.615
PXN|PAXILLIN-R-V 13739 0.005008 0.138 0.6109
YBX1|YB-1-R-V 13699 0.005754 0.138 0.6091
RAD50|RAD50-M-C 13626 0.007378 0.138 0.6058
IGF1R|IGF-1R-BETA-R-C 13625 0.007402 0.138 0.6058
MRE11A|MRE11-R-C 8891.5 0.008062 0.138 0.6047
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'

30 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 = 30
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'

kruskal_wallis_P Q
ERBB3|HER3_PY1298-R-C 1.158e-20 1.98e-18
MRE11A|MRE11-R-C 2.855e-19 2.44e-17
CHEK1|CHK1_PS345-R-C 1.017e-18 5.8e-17
STK11|LKB1-M-NA 1.927e-16 8.24e-15
EGFR|EGFR_PY1173-R-C 1.207e-15 4.13e-14
EGFR|EGFR-R-C 1.594e-15 4.54e-14
BECN1|BECLIN-G-V 3.227e-15 7.3e-14
MET|C-MET_PY1235-R-C 3.416e-15 7.3e-14
PIK3R1|PI3K-P85-R-V 1.919e-14 3.38e-13
XIAP|XIAP-R-C 1.976e-14 3.38e-13
Clinical variable #10: 'RADIATIONS_RADIATION_REGIMENINDICATION'

3 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 = 3
  Higher in YES 3
  Higher in NO 0
List of 3 genes differentially expressed by 'RADIATIONS_RADIATION_REGIMENINDICATION'

Table S18.  Get Full Table List of 3 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 0.0963 0.8375
PECAM1|CD31-M-V 595 0.001127 0.0963 0.8358
EIF4EBP1|4E-BP1_PT70-R-C 2921 0.003001 0.171 0.806
Clinical variable #11: 'COMPLETENESS_OF_RESECTION'

30 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 = 30
List of top 10 genes differentially expressed by 'COMPLETENESS_OF_RESECTION'

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

kruskal_wallis_P Q
BID|BID-R-C 0.0002745 0.0238
BCL2|BCL-2-R-NA 0.0003925 0.0238
PIK3CA|PI3K-P110-ALPHA-R-C 0.0004175 0.0238
PEA15|PEA-15-R-V 0.001877 0.0482
NCOA3|AIB1-M-V 0.002129 0.0482
PECAM1|CD31-M-V 0.002395 0.0482
MAPK14|P38_MAPK-R-C 0.002448 0.0482
BAK1|BAK-R-C 0.002495 0.0482
CDKN1B|P27-R-V 0.002667 0.0482
MRE11A|MRE11-R-C 0.002821 0.0482
Clinical variable #12: 'NUMBER_OF_LYMPH_NODES'

30 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 = 30
  pos. correlated 11
  neg. correlated 19
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 0.00104
GAB2|GAB2-R-V 0.2012 2.373e-05 0.00135
PXN|PAXILLIN-R-V 0.1963 3.737e-05 0.0016
CASP7|CASPASE-7_CLEAVEDD198-R-C -0.1931 5.035e-05 0.00172
BAX|BAX-R-V -0.183 0.0001243 0.00354
XRCC1|XRCC1-R-C -0.1801 0.0001587 0.00388
CCNE1|CYCLIN_E1-M-V -0.1611 0.0007443 0.0144
MAPK14|P38_MAPK-R-C -0.1609 0.0007586 0.0144
SRC|SRC_PY416-R-C -0.1578 0.0009571 0.0147
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

Selected clinical features

  • For clinical features selected for this analysis and their value conozzle.versions, please find a documentation on selected CDEs .

  • Survival time data

    • Survival time data is a combined value of days_to_death and days_to_last_followup. For each patient, it creates a combined value 'days_to_death_or_last_fup' using conversion process below.

      • if 'vital_status'==1(dead), 'days_to_last_followup' is always NA. Thus, uses 'days_to_death' value for 'days_to_death_or_fup'

      • if 'vital_status'==0(alive),

        • if 'days_to_death'==NA & 'days_to_last_followup'!=NA, uses 'days_to_last_followup' value for 'days_to_death_or_fup'

        • if 'days_to_death'!=NA, excludes this case in survival analysis and report the case.

      • if 'vital_status'==NA,excludes this case in survival analysis and report the case.

    • cf. In certain diesase types such as SKCM, days_to_death parameter is replaced with time_from_specimen_dx or time_from_specimen_procurement_to_death .

  • This analysis excluded clinical variables that has only NA values.

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

Wilcoxon rank sum test (Mann-Whitney U test)

For two groups (mutant or wild-type) of continuous type of clinical data, wilcoxon rank sum test (Mann and Whitney, 1947) was applied to compare their mean difference using 'wilcox.test(continuous.clinical ~ as.factor(group), exact=FALSE)' function in R. This test is equivalent to the Mann-Whitney test.

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] Mann and Whitney, On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other, Annals of Mathematical Statistics 18 (1), 50-60 (1947)
[4] 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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