Correlation between RPPA expression and clinical features
Pan-kidney cohort (KICH+KIRC+KIRP) (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
doi:10.7908/C1ZG6RG7
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/C1ZG6RG7
Overview
Introduction

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

Summary

Testing the association between 227 genes and 14 clinical features across 755 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 9 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • IGFBP2|IGFBP2 ,  SCD1|SCD1 ,  MYH9|MYOSIN-IIA-PS1943 ,  GSK3A GSK3B|GSK3-ALPHA-BETA ,  PDCD4|PDCD4 ,  ...

  • 30 genes correlated to 'PATHOLOGIC_STAGE'.

    • SRC|SRC_PY527 ,  TFRC|TFRC ,  MAPK1 MAPK3|MAPK_PT202_Y204 ,  CCNB1|CYCLIN_B1 ,  TP53BP1|53BP1 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • TFRC|TFRC ,  SRC|SRC_PY527 ,  MAPK1 MAPK3|MAPK_PT202_Y204 ,  CTNNB1|ALPHA-CATENIN ,  CDH3|P-CADHERIN ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • CCNB1|CYCLIN_B1 ,  FN1|FIBRONECTIN ,  FASN|FASN ,  CTNNB1|ALPHA-CATENIN ,  MSH6|MSH6 ,  ...

  • 30 genes correlated to 'PATHOLOGY_M_STAGE'.

    • CCNB1|CYCLIN_B1 ,  TP53BP1|53BP1 ,  TFRC|TFRC ,  ERBB3|HER3_PY1289 ,  MAPK1 MAPK3|MAPK_PT202_Y204 ,  ...

  • 29 genes correlated to 'GENDER'.

    • CLDN7|CLAUDIN-7 ,  EIF4EBP1|4E-BP1_PS65 ,  PDK1|PDK1 ,  NOTCH1|NOTCH1 ,  ANXA1|ANNEXIN-1 ,  ...

  • 2 genes correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

    • RPS6KB1|P70S6K_PT389 ,  MAP2K1|MEK1

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • CDKN1B|P27_PT198 ,  ERCC1|ERCC1 ,  IRS1|IRS1 ,  RPS6KA1|P90RSK_PT359_S363 ,  TP53|P53 ,  ...

  • 30 genes correlated to 'RACE'.

    • RAB25|RAB25 ,  FOXO3|FOXO3A_PS318_S321 ,  BRCA2|BRCA2 ,  PDK1|PDK1_PS241 ,  ITGA2|CD49B ,  ...

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'RADIATION_THERAPY', 'NUMBER_PACK_YEARS_SMOKED', 'YEAR_OF_TOBACCO_SMOKING_ONSET', 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
DAYS_TO_DEATH_OR_LAST_FUP Cox regression test   N=0        
YEARS_TO_BIRTH Spearman correlation test N=30 older N=17 younger N=13
PATHOLOGIC_STAGE 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=19 lower stage N=11
PATHOLOGY_M_STAGE Wilcoxon test N=30 class1 N=30 class0 N=0
GENDER Wilcoxon test N=29 male N=29 female N=0
RADIATION_THERAPY Wilcoxon test   N=0        
KARNOFSKY_PERFORMANCE_SCORE Spearman correlation test N=2 higher score N=1 lower score N=1
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
NUMBER_PACK_YEARS_SMOKED Spearman correlation test   N=0        
YEAR_OF_TOBACCO_SMOKING_ONSET Spearman correlation test   N=0        
RACE Kruskal-Wallis test N=30        
ETHNICITY Wilcoxon 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) 0.1-194.8 (median=36.3)
  censored N = 547
  death N = 207
     
  Significant markers N = 0
Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 60.01 (13)
  Significant markers N = 30
  pos. correlated 17
  neg. correlated 13
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
IGFBP2|IGFBP2 0.1997 3.462e-08 7.86e-06
SCD1|SCD1 0.3006 4.144e-07 4.7e-05
MYH9|MYOSIN-IIA-PS1943 -0.3042 1.077e-05 0.000815
GSK3A GSK3B|GSK3-ALPHA-BETA -0.1557 1.837e-05 0.00104
PDCD4|PDCD4 -0.1397 0.0001237 0.00561
MTCO2|MITOCHONDRIA 0.1711 0.0002528 0.00798
AR|AR -0.1322 0.0002825 0.00798
ARHI|ARHI 0.1315 0.0003281 0.00798
CDH3|P-CADHERIN 0.1303 0.0003448 0.00798
MYH11|MYH11 -0.1302 0.0003518 0.00798
Clinical variable #3: 'PATHOLOGIC_STAGE'

30 genes related to 'PATHOLOGIC_STAGE'.

Table S4.  Basic characteristics of clinical feature: 'PATHOLOGIC_STAGE'

PATHOLOGIC_STAGE Labels N
  STAGE I 383
  STAGE II 90
  STAGE III 173
  STAGE IV 101
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'PATHOLOGIC_STAGE'

Table S5.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGIC_STAGE'

kruskal_wallis_P Q
SRC|SRC_PY527 1.244e-14 2.82e-12
TFRC|TFRC 4.575e-14 5.19e-12
MAPK1 MAPK3|MAPK_PT202_Y204 1.225e-11 9.27e-10
CCNB1|CYCLIN_B1 5.306e-11 3.01e-09
TP53BP1|53BP1 9.417e-11 3.69e-09
ERBB2|HER2_PY1248 9.766e-11 3.69e-09
PECAM1|CD31 1.967e-10 6.38e-09
RAF1|C-RAF_PS338 3.078e-10 8.73e-09
ERBB3|HER3_PY1289 1.576e-09 3.98e-08
YBX1|YB-1 2.593e-09 5.89e-08
Clinical variable #4: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'

PATHOLOGY_T_STAGE Mean (SD) 1.83 (0.94)
  N
  T1 395
  T2 109
  T3 236
  T4 15
     
  Significant markers N = 30
  pos. correlated 18
  neg. correlated 12
List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S7.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
TFRC|TFRC 0.2795 5.149e-15 1.17e-12
SRC|SRC_PY527 -0.2758 1.189e-14 1.35e-12
MAPK1 MAPK3|MAPK_PT202_Y204 -0.2304 1.482e-10 1.12e-08
CTNNB1|ALPHA-CATENIN -0.3541 2.54e-10 1.44e-08
CDH3|P-CADHERIN 0.2225 6.379e-10 2.9e-08
CCNB1|CYCLIN_B1 0.2212 7.994e-10 3.02e-08
RAF1|C-RAF_PS338 -0.2178 1.461e-09 4.74e-08
PEA15|PEA15 0.2146 2.593e-09 6.96e-08
TP53BP1|53BP1 0.2142 2.758e-09 6.96e-08
YBX1|YB-1 0.2103 5.427e-09 1.23e-07
Clinical variable #5: 'PATHOLOGY_N_STAGE'

30 genes related to 'PATHOLOGY_N_STAGE'.

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY_N_STAGE'

PATHOLOGY_N_STAGE Mean (SD) 0.15 (0.4)
  N
  N0 299
  N1 39
  N2 6
     
  Significant markers N = 30
  pos. correlated 19
  neg. correlated 11
List of top 10 genes differentially expressed by 'PATHOLOGY_N_STAGE'

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

SpearmanCorr corrP Q
CCNB1|CYCLIN_B1 0.3347 1.896e-10 4.3e-08
FN1|FIBRONECTIN 0.328 4.52e-10 5.13e-08
FASN|FASN 0.2875 5.689e-08 4.3e-06
CTNNB1|ALPHA-CATENIN -0.4455 3.426e-07 1.94e-05
MSH6|MSH6 0.2596 1.054e-06 4.78e-05
PDK1|PDK1_PS241 -0.244 4.674e-06 0.000168
ASNS|ASNS 0.2429 5.173e-06 0.000168
DVL3|DVL3 0.2408 6.304e-06 0.000179
MYH11|MYH11 0.2371 8.752e-06 0.000221
EIF4EBP1|4E-BP1 0.2345 1.105e-05 0.000251
Clinical variable #6: 'PATHOLOGY_M_STAGE'

30 genes related to 'PATHOLOGY_M_STAGE'.

Table S10.  Basic characteristics of clinical feature: 'PATHOLOGY_M_STAGE'

PATHOLOGY_M_STAGE Labels N
  class0 486
  class1 86
     
  Significant markers N = 30
  Higher in class1 30
  Higher in class0 0
List of top 10 genes differentially expressed by 'PATHOLOGY_M_STAGE'

Table S11.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY_M_STAGE'

W(pos if higher in 'class1') wilcoxontestP Q AUC
CCNB1|CYCLIN_B1 29100 6.418e-09 1.46e-06 0.6962
TP53BP1|53BP1 28476 8.149e-08 8.07e-06 0.6813
TFRC|TFRC 28407 1.067e-07 8.07e-06 0.6797
ERBB3|HER3_PY1289 13503 1.657e-07 9.4e-06 0.6769
MAPK1 MAPK3|MAPK_PT202_Y204 13871 6.567e-07 2.52e-05 0.6681
PECAM1|CD31 13875 6.663e-07 2.52e-05 0.668
EEF2|EEF2 27540 2.586e-06 8.39e-05 0.6589
PIK3R1|PI3K-P85 27452 3.502e-06 8.92e-05 0.6568
ERBB2|HER2_PY1248 14347 3.538e-06 8.92e-05 0.6567
YBX1|YB-1 27418 3.933e-06 8.93e-05 0.656
Clinical variable #7: 'GENDER'

29 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 243
  MALE 512
     
  Significant markers N = 29
  Higher in MALE 29
  Higher in FEMALE 0
List of top 10 genes differentially expressed by 'GENDER'

Table S13.  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
CLDN7|CLAUDIN-7 74916 5.655e-06 0.000642 0.6021
EIF4EBP1|4E-BP1_PS65 52102 0.0003068 0.0232 0.5812
PDK1|PDK1 71560 0.0008372 0.0313 0.5752
NOTCH1|NOTCH1 52967 0.0009649 0.0313 0.5743
ANXA1|ANNEXIN-1 59705 0.0009996 0.0313 0.5778
DIABLO|SMAC 30274 0.001067 0.0313 0.5914
SERPINE1|PAI-1 71344 0.001102 0.0313 0.5734
MAPK14|P38_MAPK 21010 0.001338 0.0323 0.5896
VHL|VHL 59459 0.001423 0.0323 0.5754
EEF2|EEF2 70751 0.002279 0.047 0.5687
Clinical variable #8: 'RADIATION_THERAPY'

No gene related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 324
  YES 3
     
  Significant markers N = 0
Clinical variable #9: 'KARNOFSKY_PERFORMANCE_SCORE'

2 genes related to 'KARNOFSKY_PERFORMANCE_SCORE'.

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

KARNOFSKY_PERFORMANCE_SCORE Mean (SD) 89.74 (20)
  Significant markers N = 2
  pos. correlated 1
  neg. correlated 1
List of 2 genes differentially expressed by 'KARNOFSKY_PERFORMANCE_SCORE'

Table S16.  Get Full Table List of 2 genes significantly correlated to 'KARNOFSKY_PERFORMANCE_SCORE' by Spearman correlation test

SpearmanCorr corrP Q
RPS6KB1|P70S6K_PT389 0.3185 0.0004666 0.0966
MAP2K1|MEK1 -0.3043 0.0008509 0.0966
Clinical variable #10: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  KIDNEY CHROMOPHOBE 63
  KIDNEY CLEAR CELL RENAL CARCINOMA 478
  KIDNEY PAPILLARY RENAL CELL CARCINOMA 214
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S18.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

kruskal_wallis_P Q
CDKN1B|P27_PT198 3.195e-11 7.25e-09
ERCC1|ERCC1 8.767e-10 9.95e-08
IRS1|IRS1 1.054e-08 7.98e-07
RPS6KA1|P90RSK_PT359_S363 1.414e-08 8.02e-07
TP53|P53 1.938e-06 8.8e-05
ESR1|ER-ALPHA_PS118 3.707e-06 0.000121
CDC2|CDK1 3.722e-06 0.000121
EGFR|EGFR 5.345e-06 0.000152
PDK1|PDK1 1.328e-05 0.000335
EIF4EBP1|4E-BP1_PS65 7.2e-05 0.00163
Clinical variable #11: 'NUMBER_PACK_YEARS_SMOKED'

No gene related to 'NUMBER_PACK_YEARS_SMOKED'.

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

NUMBER_PACK_YEARS_SMOKED Mean (SD) 29.79 (24)
  Significant markers N = 0
Clinical variable #12: 'YEAR_OF_TOBACCO_SMOKING_ONSET'

No gene related to 'YEAR_OF_TOBACCO_SMOKING_ONSET'.

Table S20.  Basic characteristics of clinical feature: 'YEAR_OF_TOBACCO_SMOKING_ONSET'

YEAR_OF_TOBACCO_SMOKING_ONSET Mean (SD) 1971.68 (15)
  Significant markers N = 0
Clinical variable #13: 'RACE'

30 genes related to 'RACE'.

Table S21.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 15
  BLACK OR AFRICAN AMERICAN 93
  WHITE 625
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S22.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
RAB25|RAB25 4.258e-05 0.00967
FOXO3|FOXO3A_PS318_S321 0.000159 0.018
BRCA2|BRCA2 0.0003904 0.0295
PDK1|PDK1_PS241 0.0008623 0.0489
ITGA2|CD49B 0.001117 0.0507
C12ORF5|TIGAR 0.002623 0.0992
STMN1|STATHMIN 0.003518 0.102
ESR1|ER-ALPHA_PS118 0.003788 0.102
FOXO3|FOXO3A 0.00403 0.102
IRS1|IRS1 0.004674 0.106
Clinical variable #14: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 32
  NOT HISPANIC OR LATINO 522
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 755

  • Number of genes = 227

  • Number of clinical features = 14

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, 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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