Correlation between RPPA expression and clinical features
Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
doi:10.7908/C16M362N
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/C16M362N
Overview
Introduction

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

Summary

Testing the association between 195 genes and 12 clinical features across 214 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 8 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • RPS6KB1|P70S6K_PT389 ,  SCD1|SCD1 ,  PECAM1|CD31 ,  NRAS|N-RAS ,  TP53|P53 ,  ...

  • 30 genes correlated to 'PATHOLOGIC_STAGE'.

    • CTNNB1|ALPHA-CATENIN ,  CCNB1|CYCLIN_B1 ,  YWHAE|14-3-3_EPSILON ,  FN1|FIBRONECTIN ,  CLDN7|CLAUDIN-7 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • CTNNB1|ALPHA-CATENIN ,  FN1|FIBRONECTIN ,  CCNB1|CYCLIN_B1 ,  VHL|VHL ,  CLDN7|CLAUDIN-7 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

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

  • 28 genes correlated to 'PATHOLOGY_M_STAGE'.

    • CTNNB1|ALPHA-CATENIN ,  FASN|FASN ,  YWHAE|14-3-3_EPSILON ,  TFRC|TFRC ,  ANXA7 |ANNEXIN_VII ,  ...

  • 28 genes correlated to 'GENDER'.

    • YWHAE|14-3-3_EPSILON ,  PDK1|PDK1 ,  RICTOR|RICTOR ,  MSH6|MSH6 ,  ANXA7 |ANNEXIN_VII ,  ...

  • 13 genes correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

    • MAP2K1|MEK1 ,  ANXA1|ANNEXIN-1 ,  GAB2|GAB2 ,  EIF4EBP1|4E-BP1 ,  CTNNB1|ALPHA-CATENIN ,  ...

  • 1 gene correlated to 'ETHNICITY'.

    • RB1|RB_PS807_S811

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'NUMBER_PACK_YEARS_SMOKED', 'YEAR_OF_TOBACCO_SMOKING_ONSET', 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=30 older N=21 younger N=9
PATHOLOGIC_STAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=14 lower stage N=16
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=14 lower stage N=16
PATHOLOGY_M_STAGE Wilcoxon test N=28 class1 N=28 class0 N=0
GENDER Wilcoxon test N=28 male N=28 female N=0
KARNOFSKY_PERFORMANCE_SCORE Spearman correlation test N=13 higher score N=8 lower score N=5
NUMBER_PACK_YEARS_SMOKED Spearman correlation test   N=0        
YEAR_OF_TOBACCO_SMOKING_ONSET Spearman correlation test   N=0        
RACE Kruskal-Wallis test   N=0        
ETHNICITY Wilcoxon test N=1 not hispanic or latino N=1 hispanic or latino 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=24.5)
  censored N = 181
  death N = 32
     
  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) 61.55 (12)
  Significant markers N = 30
  pos. correlated 21
  neg. correlated 9
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
RPS6KB1|P70S6K_PT389 0.3946 3.09e-09 6.03e-07
SCD1|SCD1 0.3257 1.407e-06 9.78e-05
PECAM1|CD31 0.3249 1.505e-06 9.78e-05
NRAS|N-RAS 0.3208 2.065e-06 0.000101
TP53|P53 0.3164 2.892e-06 0.000112
BECN1|BECLIN 0.3141 3.445e-06 0.000112
SMAD4|SMAD4 0.3113 4.231e-06 0.000116
ARHI|ARHI 0.3156 4.771e-06 0.000116
FOXO3|FOXO3A 0.3067 5.977e-06 0.00013
BAK1|BAK 0.3004 9.444e-06 0.000174
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 129
  STAGE II 17
  STAGE III 46
  STAGE IV 14
     
  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
CTNNB1|ALPHA-CATENIN 2.169e-09 4.23e-07
CCNB1|CYCLIN_B1 2.265e-06 0.000221
YWHAE|14-3-3_EPSILON 4.78e-06 0.000305
FN1|FIBRONECTIN 6.25e-06 0.000305
CLDN7|CLAUDIN-7 1.001e-05 0.00039
RICTOR|RICTOR 1.261e-05 0.00041
SQSTM1|P62-LCK-LIGAND 2.276e-05 0.000615
G6PD|G6PD 2.769e-05 0.000615
FRAP1|MTOR_PS2448 3.068e-05 0.000615
MSH6|MSH6 3.153e-05 0.000615
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) 1.62 (0.88)
  N
  T1 136
  T2 25
  T3 51
  T4 2
     
  Significant markers N = 30
  pos. correlated 14
  neg. correlated 16
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
CTNNB1|ALPHA-CATENIN -0.4392 1.664e-11 3.25e-09
FN1|FIBRONECTIN 0.3687 2.717e-08 2.65e-06
CCNB1|CYCLIN_B1 0.3415 3.024e-07 1.97e-05
VHL|VHL -0.3355 5.021e-07 2.45e-05
CLDN7|CLAUDIN-7 -0.325 1.179e-06 4.6e-05
SQSTM1|P62-LCK-LIGAND 0.3141 2.771e-06 9.01e-05
G6PD|G6PD 0.3119 3.274e-06 9.12e-05
RICTOR|RICTOR 0.3007 7.577e-06 0.000185
FRAP1|MTOR_PS2448 -0.297 9.892e-06 0.000214
EIF4G1|EIF4G 0.2894 1.702e-05 0.000332
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) 0.41 (0.6)
  N
  N0 46
  N1 21
  N2 4
     
  Significant markers N = 30
  pos. correlated 14
  neg. correlated 16
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
FN1|FIBRONECTIN 0.5211 3.18e-06 0.000349
MSH6|MSH6 0.5187 3.579e-06 0.000349
VHL|VHL -0.4682 3.827e-05 0.00249
CTNNB1|ALPHA-CATENIN -0.4586 5.78e-05 0.00282
FASN|FASN 0.4338 0.0001571 0.00613
CLDN7|CLAUDIN-7 -0.413 0.0003442 0.00964
IGFBP2|IGFBP2 0.4129 0.0003462 0.00964
YWHAE|14-3-3_EPSILON -0.4016 0.0005183 0.0126
CCNB1|CYCLIN_B1 0.3938 0.0006785 0.0147
PARK7|DJ-1 -0.3794 0.001102 0.0201
Clinical variable #6: 'PATHOLOGY_M_STAGE'

28 genes related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 72
  class1 8
     
  Significant markers N = 28
  Higher in class1 28
  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
CTNNB1|ALPHA-CATENIN 74 0.000617 0.12 0.8715
FASN|FASN 486 0.001538 0.15 0.8438
YWHAE|14-3-3_EPSILON 109 0.004201 0.167 0.8108
TFRC|TFRC 467 0.004201 0.167 0.8108
ANXA7 |ANNEXIN_VII 112 0.004884 0.167 0.8056
FOXO3|FOXO3A_PS318_S321 113 0.005133 0.167 0.8038
SCD1|SCD1 120 0.007225 0.185 0.7917
MSH6|MSH6 452 0.008738 0.185 0.7847
RICTOR|RICTOR 452 0.008738 0.185 0.7847
CCNE1|CYCLIN_E1 445 0.01208 0.185 0.7726
Clinical variable #7: 'GENDER'

28 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 56
  MALE 158
     
  Significant markers N = 28
  Higher in MALE 28
  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'. 2 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
YWHAE|14-3-3_EPSILON 6197 8.516e-06 0.00088 0.7004
PDK1|PDK1 6192 9.028e-06 0.00088 0.6998
RICTOR|RICTOR 2855 8.168e-05 0.00531 0.6773
MSH6|MSH6 2940 0.0001946 0.00949 0.6677
ANXA7 |ANNEXIN_VII 5869 0.0002856 0.0105 0.6633
IGFBP2|IGFBP2 3045 0.0005357 0.0149 0.6559
EGFR|EGFR_PY1173 5741 0.0009447 0.023 0.6488
CLDN7|CLAUDIN-7 5688 0.001507 0.0326 0.6429
CCNE1|CYCLIN_E1 3184 0.001851 0.0361 0.6401
MET|C-MET_PY1235 5637 0.002324 0.0412 0.6371
Clinical variable #8: 'KARNOFSKY_PERFORMANCE_SCORE'

13 genes related to 'KARNOFSKY_PERFORMANCE_SCORE'.

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

KARNOFSKY_PERFORMANCE_SCORE Mean (SD) 89.14 (21)
  Significant markers N = 13
  pos. correlated 8
  neg. correlated 5
List of top 10 genes differentially expressed by 'KARNOFSKY_PERFORMANCE_SCORE'

Table S15.  Get Full Table List of top 10 genes significantly correlated to 'KARNOFSKY_PERFORMANCE_SCORE' by Spearman correlation test

SpearmanCorr corrP Q
MAP2K1|MEK1 -0.5156 3.437e-05 0.0067
ANXA1|ANNEXIN-1 0.3677 0.004519 0.191
GAB2|GAB2 -0.3629 0.005118 0.191
EIF4EBP1|4E-BP1 -0.3605 0.005445 0.191
CTNNB1|ALPHA-CATENIN 0.3555 0.006166 0.191
YWHAE|14-3-3_EPSILON 0.3523 0.006678 0.191
RAB25|RAB25 0.3466 0.007695 0.191
CAV1|CAVEOLIN-1 -0.3458 0.007848 0.191
FN1|FIBRONECTIN -0.3365 0.009791 0.212
RPS6KB1|P70S6K_PT389 0.3255 0.01265 0.247
Clinical variable #9: 'NUMBER_PACK_YEARS_SMOKED'

No gene related to 'NUMBER_PACK_YEARS_SMOKED'.

Table S16.  Basic characteristics of clinical feature: 'NUMBER_PACK_YEARS_SMOKED'

NUMBER_PACK_YEARS_SMOKED Mean (SD) 31.25 (27)
  Significant markers N = 0
Clinical variable #10: 'YEAR_OF_TOBACCO_SMOKING_ONSET'

No gene related to 'YEAR_OF_TOBACCO_SMOKING_ONSET'.

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

YEAR_OF_TOBACCO_SMOKING_ONSET Mean (SD) 1970.13 (15)
  Significant markers N = 0
Clinical variable #11: 'RACE'

No gene related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 5
  BLACK OR AFRICAN AMERICAN 45
  WHITE 150
     
  Significant markers N = 0
Clinical variable #12: 'ETHNICITY'

One gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 7
  NOT HISPANIC OR LATINO 176
     
  Significant markers N = 1
  Higher in NOT HISPANIC OR LATINO 1
  Higher in HISPANIC OR LATINO 0
List of one gene differentially expressed by 'ETHNICITY'

Table S20.  Get Full Table List of one gene differentially expressed by 'ETHNICITY'

W(pos if higher in 'NOT HISPANIC OR LATINO') wilcoxontestP Q AUC
RB1|RB_PS807_S811 c("160", "0.0009194") c("160", "0.0009194") 0.179 0.8701
Methods & Data
Input

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

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

  • Number of patients = 214

  • Number of genes = 195

  • Number of clinical features = 12

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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