Correlation between RPPA expression and clinical features
Bladder Urothelial Carcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C1251HHQ
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between RPPA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1251HHQ
Overview
Introduction

This pipeline uses various statistical tests to identify RPPAs whose expression levels correlated to selected clinical features. The input file "BLCA-TP.rppa.txt" is generated in the pipeline RPPA_AnnotateWithGene in the stddata run.

Summary

Testing the association between 208 genes and 13 clinical features across 344 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 12 clinical features related to at least one genes.

  • 17 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • SRSF1|SF2 ,  SCD|SCD ,  ANXA1|ANNEXIN-1 ,  EGFR|EGFR ,  BAP1|BAP1-C-4 ,  ...

  • 11 genes correlated to 'YEARS_TO_BIRTH'.

    • RPTOR|RAPTOR ,  EIF4EBP1|4E-BP1_PT37_T46 ,  TUBA1B|ACETYL-A-TUBULIN-LYS40 ,  PEA15|PEA15 ,  SMAD3|SMAD3 ,  ...

  • 30 genes correlated to 'PATHOLOGIC_STAGE'.

    • EIF4EBP1|4E-BP1_PT37_T46 ,  PEA15|PEA15 ,  EGFR|EGFR_PY1068 ,  FN1|FIBRONECTIN ,  CTNNA1|ALPHA-CATENIN ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • WWTR1|TAZ ,  PEA15|PEA15 ,  FN1|FIBRONECTIN ,  CTNNA1|ALPHA-CATENIN ,  SRSF1|SF2 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • YBX1|YB-1 ,  CTNNA1|ALPHA-CATENIN ,  RPS6|S6_PS240_S244 ,  RPS6KA1|P90RSK ,  MYH11|MYH11 ,  ...

  • 3 genes correlated to 'PATHOLOGY_M_STAGE'.

    • RAB11A RAB11B|RAB11 ,  BECN1|BECLIN ,  CTNNA1|ALPHA-CATENIN

  • 29 genes correlated to 'GENDER'.

    • CAV1|CAVEOLIN-1 ,  RAF1|C-RAF ,  MYH11|MYH11 ,  YWHAE|14-3-3_EPSILON ,  BAP1|BAP1-C-4 ,  ...

  • 29 genes correlated to 'RADIATION_THERAPY'.

    • GAB2|GAB2 ,  PEA15|PEA15 ,  SRC|SRC_PY416 ,  CLDN7|CLAUDIN-7 ,  RPTOR|RAPTOR ,  ...

  • 30 genes correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

    • YBX1|YB-1 ,  SRC|SRC ,  CDH1|E-CADHERIN ,  ERBB3|HER3 ,  CLDN7|CLAUDIN-7 ,  ...

  • 3 genes correlated to 'NUMBER_PACK_YEARS_SMOKED'.

    • EIF4E|EIF4E ,  SRSF1|SF2 ,  MAP2K1|MEK1

  • 30 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

    • RPS6|S6_PS240_S244 ,  INPP4B|INPP4B ,  RPS6|S6_PS235_S236 ,  MYH11|MYH11 ,  CTNNA1|ALPHA-CATENIN ,  ...

  • 30 genes correlated to 'RACE'.

    • FN1|FIBRONECTIN ,  YBX1|YB-1 ,  CDH1|E-CADHERIN ,  WWTR1|TAZ ,  PDCD4|PDCD4 ,  ...

  • No genes correlated to '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
DAYS_TO_DEATH_OR_LAST_FUP Cox regression test N=17   N=NA   N=NA
YEARS_TO_BIRTH Spearman correlation test N=11 older N=8 younger N=3
PATHOLOGIC_STAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=16 lower stage N=14
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=16 lower stage N=14
PATHOLOGY_M_STAGE Wilcoxon test N=3 class1 N=3 class0 N=0
GENDER Wilcoxon test N=29 male N=29 female N=0
RADIATION_THERAPY Wilcoxon test N=29 yes N=29 no N=0
KARNOFSKY_PERFORMANCE_SCORE Spearman correlation test N=30 higher score N=9 lower score N=21
NUMBER_PACK_YEARS_SMOKED Spearman correlation test N=3 higher number_pack_years_smoked N=2 lower number_pack_years_smoked N=1
NUMBER_OF_LYMPH_NODES Spearman correlation test N=30 higher number_of_lymph_nodes N=15 lower number_of_lymph_nodes N=15
RACE Kruskal-Wallis test N=30        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

17 genes 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) 0.4-166 (median=17.6)
  censored N = 186
  death N = 157
     
  Significant markers N = 17
  associated with shorter survival NA
  associated with longer survival NA
List of top 10 genes differentially expressed by 'DAYS_TO_DEATH_OR_LAST_FUP'

Table S2.  Get Full Table List of top 10 genes significantly associated with 'Time to Death' by Cox regression test. For the survival curves, it compared quantile intervals at c(0, 0.25, 0.50, 0.75, 1) and did not try survival analysis if there is only one interval.

logrank_P Q C_index
SRSF1|SF2 0.000557 0.057 0.43
SCD|SCD 0.000639 0.057 0.432
ANXA1|ANNEXIN-1 0.00101 0.057 0.611
EGFR|EGFR 0.00109 0.057 0.579
BAP1|BAP1-C-4 0.00236 0.098 0.47
SMAD3|SMAD3 0.00413 0.14 0.418
GATA3|GATA3 0.00515 0.15 0.41
SRC|SRC 0.00649 0.17 0.409
RPS6KA1|P90RSK 0.00741 0.17 0.44
GAB2|GAB2 0.00875 0.18 0.546
Clinical variable #2: 'YEARS_TO_BIRTH'

11 genes related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 67.85 (11)
  Significant markers N = 11
  pos. correlated 8
  neg. correlated 3
List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

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

SpearmanCorr corrP Q
RPTOR|RAPTOR 0.2187 4.396e-05 0.00914
EIF4EBP1|4E-BP1_PT37_T46 -0.1672 0.00189 0.197
TUBA1B|ACETYL-A-TUBULIN-LYS40 0.1543 0.004182 0.228
PEA15|PEA15 0.1535 0.004392 0.228
SMAD3|SMAD3 -0.1456 0.006912 0.288
ANXA1|ANNEXIN-1 0.1403 0.009285 0.291
YBX1|YB-1 0.1378 0.01065 0.291
PRDX1|PRDX1 0.1362 0.01157 0.291
STAT3|STAT3_PY705 0.1331 0.0136 0.291
CASP8|CASPASE-8 -0.1308 0.01533 0.291
Clinical variable #3: 'PATHOLOGIC_STAGE'

30 genes related to 'PATHOLOGIC_STAGE'.

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGIC_STAGE'

PATHOLOGIC_STAGE Labels N
  STAGE I 2
  STAGE II 105
  STAGE III 119
  STAGE IV 116
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'PATHOLOGIC_STAGE'

Table S6.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGIC_STAGE'

kruskal_wallis_P Q
EIF4EBP1|4E-BP1_PT37_T46 2.488e-08 2.6e-06
PEA15|PEA15 2.503e-08 2.6e-06
EGFR|EGFR_PY1068 6.664e-08 4.62e-06
FN1|FIBRONECTIN 3.982e-07 2.07e-05
CTNNA1|ALPHA-CATENIN 5.14e-07 2.14e-05
RPTOR|RAPTOR 1.478e-06 5.12e-05
SRC|SRC_PY416 1.792e-06 5.33e-05
SRSF1|SF2 2.52e-06 6.55e-05
YBX1|YB-1 3.301e-06 7.63e-05
JUN|C-JUN_PS73 4.479e-05 0.000932
Clinical variable #4: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'

PATHOLOGY_T_STAGE Mean (SD) 2.82 (0.69)
  N
  T0 1
  T1 2
  T2 97
  T3 169
  T4 48
     
  Significant markers N = 30
  pos. correlated 16
  neg. correlated 14
List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S8.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
WWTR1|TAZ 0.2766 5.63e-07 7.16e-05
PEA15|PEA15 0.2746 6.881e-07 7.16e-05
FN1|FIBRONECTIN 0.2679 1.301e-06 8.15e-05
CTNNA1|ALPHA-CATENIN -0.3266 1.567e-06 8.15e-05
SRSF1|SF2 -0.2532 5.009e-06 0.000178
SRC|SRC_PY416 -0.2529 5.147e-06 0.000178
EIF4EBP1|4E-BP1_PT37_T46 -0.2464 9.035e-06 0.000268
COL6A1|COLLAGEN_VI 0.2442 1.092e-05 0.000284
MYH11|MYH11 0.2364 2.11e-05 0.000476
BID|BID 0.2354 2.291e-05 0.000476
Clinical variable #5: 'PATHOLOGY_N_STAGE'

30 genes related to 'PATHOLOGY_N_STAGE'.

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY_N_STAGE'

PATHOLOGY_N_STAGE Mean (SD) 0.61 (0.89)
  N
  N0 201
  N1 39
  N2 66
  N3 7
     
  Significant markers N = 30
  pos. correlated 16
  neg. correlated 14
List of top 10 genes differentially expressed by 'PATHOLOGY_N_STAGE'

Table S10.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_N_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
YBX1|YB-1 0.2555 4.665e-06 0.00058
CTNNA1|ALPHA-CATENIN -0.3172 5.574e-06 0.00058
RPS6|S6_PS240_S244 -0.2475 9.427e-06 0.000654
RPS6KA1|P90RSK -0.2206 8.319e-05 0.00433
MYH11|MYH11 0.2077 0.0002156 0.00806
PEA15|PEA15 0.2066 0.0002324 0.00806
RPS6|S6_PS235_S236 -0.2015 0.0003346 0.00994
CAV1|CAVEOLIN-1 0.1988 0.0004022 0.0105
TGM2|TRANSGLUTAMINASE 0.1925 0.0006166 0.0143
SRC|SRC_PY416 -0.1878 0.000839 0.016
Clinical variable #6: 'PATHOLOGY_M_STAGE'

3 genes related to 'PATHOLOGY_M_STAGE'.

Table S11.  Basic characteristics of clinical feature: 'PATHOLOGY_M_STAGE'

PATHOLOGY_M_STAGE Labels N
  class0 163
  class1 10
     
  Significant markers N = 3
  Higher in class1 3
  Higher in class0 0
List of 3 genes differentially expressed by 'PATHOLOGY_M_STAGE'

Table S12.  Get Full Table List of 3 genes differentially expressed by 'PATHOLOGY_M_STAGE'

W(pos if higher in 'class1') wilcoxontestP Q AUC
RAB11A RAB11B|RAB11 1296 0.001775 0.172 0.7951
BECN1|BECLIN 1281 0.002463 0.172 0.7859
CTNNA1|ALPHA-CATENIN 43 0.002486 0.172 0.9044
Clinical variable #7: 'GENDER'

29 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 85
  MALE 259
     
  Significant markers N = 29
  Higher in MALE 29
  Higher in FEMALE 0
List of top 10 genes differentially expressed by 'GENDER'

Table S14.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'. 1 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
CAV1|CAVEOLIN-1 8279 0.0006058 0.126 0.6239
RAF1|C-RAF 13492 0.001794 0.18 0.6129
MYH11|MYH11 8675 0.003376 0.18 0.606
YWHAE|14-3-3_EPSILON 13252 0.004793 0.18 0.602
BAP1|BAP1-C-4 13244 0.004945 0.18 0.6016
TP53BP1|53BP1 13207 0.005709 0.18 0.5999
JUN|C-JUN_PS73 13157 0.006909 0.18 0.5976
TGM2|TRANSGLUTAMINASE 8859 0.006935 0.18 0.5976
LCK|LCK 8897 0.007997 0.185 0.5959
SRC|SRC 12953 0.01449 0.273 0.5884
Clinical variable #8: 'RADIATION_THERAPY'

29 genes related to 'RADIATION_THERAPY'.

Table S15.  Basic characteristics of clinical feature: 'RADIATION_THERAPY'

RADIATION_THERAPY Labels N
  NO 306
  YES 14
     
  Significant markers N = 29
  Higher in YES 29
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATION_THERAPY'

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

W(pos if higher in 'YES') wilcoxontestP Q AUC
GAB2|GAB2 853 0.0001411 0.0293 0.8009
PEA15|PEA15 1064 0.001458 0.142 0.7516
SRC|SRC_PY416 3145 0.003062 0.142 0.7341
CLDN7|CLAUDIN-7 3141 0.003182 0.142 0.7332
RPTOR|RAPTOR 1171 0.004145 0.142 0.7267
TUBA1B|ACETYL-A-TUBULIN-LYS40 1186 0.004764 0.142 0.7232
CCNB1|CYCLIN_B1 1200 0.005416 0.142 0.7199
FOXM1|FOXM1 1216 0.006258 0.142 0.7162
VHL|VHL 3063 0.006544 0.142 0.715
CHEK1|CHK1 1226 0.006843 0.142 0.7138
Clinical variable #9: 'KARNOFSKY_PERFORMANCE_SCORE'

30 genes related to 'KARNOFSKY_PERFORMANCE_SCORE'.

Table S17.  Basic characteristics of clinical feature: 'KARNOFSKY_PERFORMANCE_SCORE'

KARNOFSKY_PERFORMANCE_SCORE Mean (SD) 83.68 (13)
  Significant markers N = 30
  pos. correlated 9
  neg. correlated 21
List of top 10 genes differentially expressed by 'KARNOFSKY_PERFORMANCE_SCORE'

Table S18.  Get Full Table List of top 10 genes significantly correlated to 'KARNOFSKY_PERFORMANCE_SCORE' by Spearman correlation test

SpearmanCorr corrP Q
YBX1|YB-1 0.3417 0.0001626 0.0146
SRC|SRC -0.3308 0.0002695 0.0146
CDH1|E-CADHERIN -0.3287 0.0002971 0.0146
ERBB3|HER3 -0.3263 0.0003307 0.0146
CLDN7|CLAUDIN-7 -0.325 0.0003504 0.0146
COPS5|JAB1 -0.379 0.0004466 0.0155
CTNNB1|BETA-CATENIN -0.3117 0.0006227 0.0185
FN1|FIBRONECTIN 0.3048 0.0008328 0.0206
PEA15|PEA15 0.3032 0.0008914 0.0206
DIABLO|SMAC -0.2952 0.001232 0.0256
Clinical variable #10: 'NUMBER_PACK_YEARS_SMOKED'

3 genes related to 'NUMBER_PACK_YEARS_SMOKED'.

Table S19.  Basic characteristics of clinical feature: 'NUMBER_PACK_YEARS_SMOKED'

NUMBER_PACK_YEARS_SMOKED Mean (SD) 39.83 (57)
  Significant markers N = 3
  pos. correlated 2
  neg. correlated 1
List of 3 genes differentially expressed by 'NUMBER_PACK_YEARS_SMOKED'

Table S20.  Get Full Table List of 3 genes significantly correlated to 'NUMBER_PACK_YEARS_SMOKED' by Spearman correlation test

SpearmanCorr corrP Q
EIF4E|EIF4E 0.2571 0.0003818 0.0794
SRSF1|SF2 -0.2421 0.000844 0.0878
MAP2K1|MEK1 0.2163 0.002942 0.204
Clinical variable #11: '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) 2.22 (7.5)
  Significant markers N = 30
  pos. correlated 15
  neg. correlated 15
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
RPS6|S6_PS240_S244 -0.2484 6.485e-05 0.0135
INPP4B|INPP4B 0.2159 0.0005446 0.0566
RPS6|S6_PS235_S236 -0.2023 0.001218 0.0844
MYH11|MYH11 0.1933 0.002016 0.0946
CTNNA1|ALPHA-CATENIN -0.2382 0.002273 0.0946
CHEK2|CHK2 -0.1862 0.002943 0.102
RPS6KA1|P90RSK -0.1791 0.004259 0.112
CCNB1|CYCLIN_B1 -0.1782 0.004476 0.112
ERBB2|HER2 0.1765 0.004865 0.112
RICTOR|RICTOR 0.174 0.005524 0.115
Clinical variable #12: 'RACE'

30 genes related to 'RACE'.

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

RACE Labels N
  ASIAN 40
  BLACK OR AFRICAN AMERICAN 20
  WHITE 268
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S24.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
FN1|FIBRONECTIN 6.684e-11 1.39e-08
YBX1|YB-1 4.381e-09 4.56e-07
CDH1|E-CADHERIN 2.748e-07 1.3e-05
WWTR1|TAZ 2.958e-07 1.3e-05
PDCD4|PDCD4 3.125e-07 1.3e-05
CTNNB1|BETA-CATENIN 1.794e-06 6.22e-05
STMN1|STATHMIN 2.709e-06 8.05e-05
TIGAR|TIGAR 3.107e-06 8.08e-05
SERPINE1|PAI-1 8.446e-06 0.000177
CAV1|CAVEOLIN-1 8.507e-06 0.000177
Clinical variable #13: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 8
  NOT HISPANIC OR LATINO 305
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 344

  • Number of genes = 208

  • Number of clinical features = 13

Selected clinical features

  • Further details on clinical features selected for this analysis, please find a documentation on selected CDEs (Clinical Data Elements). The first column of the file is a formula to convert values and the second column is a clinical parameter name.

  • 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, logrank test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values comparing quantile intervals using the 'coxph' function in R. Kaplan-Meier survival curves were plotted using quantile intervals at c(0, 0.25, 0.50, 0.75, 1). If there is only one interval group, it will not try survival analysis.

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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