Correlation between RPPA expression and clinical features
Esophageal Carcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
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/C1S46R90
Overview
Introduction

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

Summary

Testing the association between 192 genes and 14 clinical features across 126 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 7 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • C12ORF5|TIGAR ,  SRC|SRC_PY527 ,  NOTCH1|NOTCH1 ,  SRC|SRC ,  RAB25|RAB25 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • RPS6|S6_PS240_S244 ,  KIT|C-KIT ,  CHEK2|CHK2 ,  RPTOR|RAPTOR ,  CLDN7|CLAUDIN-7 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • EEF2|EEF2 ,  NDRG1|NDRG1_PT346 ,  RPS6KB1|P70S6K_PT389 ,  EGFR|EGFR ,  PIK3CA |PI3K-P110-ALPHA ,  ...

  • 4 genes correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

    • CDKN1A|P21 ,  PIK3CA |PI3K-P110-ALPHA ,  RAF1|C-RAF ,  EIF4EBP1|4E-BP1_PT37_T46

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • C12ORF5|TIGAR ,  SRC|SRC_PY527 ,  SRC|SRC ,  FN1|FIBRONECTIN ,  PIK3CA |PI3K-P110-ALPHA ,  ...

  • 6 genes correlated to 'NUMBER_PACK_YEARS_SMOKED'.

    • CCNB1|CYCLIN_B1 ,  FASN|FASN ,  ACACA|ACC1 ,  KIT|C-KIT ,  BCL2L1|BCL-XL ,  ...

  • 30 genes correlated to 'RACE'.

    • PIK3CA |PI3K-P110-ALPHA ,  SRC|SRC_PY527 ,  C12ORF5|TIGAR ,  G6PD|G6PD ,  FRAP1|MTOR_PS2448 ,  ...

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'PATHOLOGIC_STAGE', 'PATHOLOGY_M_STAGE', 'GENDER', 'RADIATION_THERAPY', 'RESIDUAL_TUMOR', and 'NUMBER_OF_LYMPH_NODES'.

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=0        
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=15 lower stage N=15
PATHOLOGY_M_STAGE Wilcoxon test   N=0        
GENDER Wilcoxon test   N=0        
RADIATION_THERAPY Wilcoxon test   N=0        
KARNOFSKY_PERFORMANCE_SCORE Spearman correlation test N=4 higher score N=2 lower score N=2
HISTOLOGICAL_TYPE Wilcoxon test N=30 esophagus squamous cell carcinoma N=30 esophagus adenocarcinoma, nos N=0
NUMBER_PACK_YEARS_SMOKED Spearman correlation test N=6 higher number_pack_years_smoked N=3 lower number_pack_years_smoked N=3
RESIDUAL_TUMOR Kruskal-Wallis test   N=0        
NUMBER_OF_LYMPH_NODES Spearman correlation test   N=0        
RACE Kruskal-Wallis test N=30        
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) 0.1-122.1 (median=13.2)
  censored N = 81
  death N = 44
     
  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) 62.71 (11)
  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
C12ORF5|TIGAR 0.4234 7.819e-07 0.00015
SRC|SRC_PY527 0.3892 6.663e-06 0.00064
NOTCH1|NOTCH1 -0.3815 1.043e-05 0.000668
SRC|SRC 0.3269 0.0001873 0.00899
RAB25|RAB25 0.3205 0.000253 0.00972
PRKCD|PKC-DELTA_PS664 0.2993 0.0006615 0.0195
BIRC2 |CIAP 0.2977 0.0007099 0.0195
PKC|PKC-PAN_BETAII_PS660 0.2791 0.001555 0.0368
SRC|SRC_PY416 0.2755 0.001794 0.0368
TUBA1B|ACETYL-A-TUBULIN-LYS40 -0.2739 0.001916 0.0368
Clinical variable #3: 'PATHOLOGIC_STAGE'

No gene related to 'PATHOLOGIC_STAGE'.

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

PATHOLOGIC_STAGE Labels N
  STAGE I 6
  STAGE IA 3
  STAGE IB 4
  STAGE II 1
  STAGE IIA 42
  STAGE IIB 23
  STAGE III 17
  STAGE IIIA 12
  STAGE IIIB 7
  STAGE IIIC 2
  STAGE IV 3
  STAGE IVA 1
     
  Significant markers N = 0
Clinical variable #4: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

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

PATHOLOGY_T_STAGE Mean (SD) 2.44 (0.76)
  N
  T1 18
  T2 35
  T3 69
  T4 2
     
  Significant markers N = 30
  pos. correlated 16
  neg. correlated 14
List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S6.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
RPS6|S6_PS240_S244 -0.312 0.0004185 0.0804
KIT|C-KIT 0.2675 0.00267 0.119
CHEK2|CHK2 -0.2663 0.002789 0.119
RPTOR|RAPTOR 0.2555 0.004186 0.119
CLDN7|CLAUDIN-7 -0.2551 0.004238 0.119
RPS6|S6_PS235_S236 -0.2545 0.004336 0.119
RB1|RB_PS807_S811 -0.2545 0.00434 0.119
TGM2|TRANSGLUTAMINASE 0.2493 0.005238 0.119
PEA15|PEA15 0.2475 0.005588 0.119
ACACA ACACB|ACC_PS79 -0.2412 0.006962 0.134
Clinical variable #5: 'PATHOLOGY_N_STAGE'

30 genes related to 'PATHOLOGY_N_STAGE'.

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

PATHOLOGY_N_STAGE Mean (SD) 0.62 (0.73)
  N
  N0 62
  N1 49
  N2 9
  N3 3
     
  Significant markers N = 30
  pos. correlated 15
  neg. correlated 15
List of top 10 genes differentially expressed by 'PATHOLOGY_N_STAGE'

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

SpearmanCorr corrP Q
EEF2|EEF2 -0.3018 0.0006919 0.104
NDRG1|NDRG1_PT346 -0.2835 0.001483 0.104
RPS6KB1|P70S6K_PT389 0.2762 0.001986 0.104
EGFR|EGFR -0.2739 0.002175 0.104
PIK3CA |PI3K-P110-ALPHA -0.2539 0.0046 0.177
DVL3|DVL3 -0.2405 0.007365 0.217
BECN1|BECLIN 0.2369 0.008331 0.217
RB1|RB_PS807_S811 -0.2333 0.00941 0.217
TSC1|TSC1 0.2304 0.01035 0.217
GAB2|GAB2 0.2277 0.01133 0.217
Clinical variable #6: 'PATHOLOGY_M_STAGE'

No gene related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 105
  class1 4
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

No gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 18
  MALE 108
     
  Significant markers N = 0
Clinical variable #8: 'RADIATION_THERAPY'

No gene related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 84
  YES 32
     
  Significant markers N = 0
Clinical variable #9: 'KARNOFSKY_PERFORMANCE_SCORE'

4 genes related to 'KARNOFSKY_PERFORMANCE_SCORE'.

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

KARNOFSKY_PERFORMANCE_SCORE Mean (SD) 69.17 (16)
  Significant markers N = 4
  pos. correlated 2
  neg. correlated 2
List of 4 genes differentially expressed by 'KARNOFSKY_PERFORMANCE_SCORE'

Table S13.  Get Full Table List of 4 genes significantly correlated to 'KARNOFSKY_PERFORMANCE_SCORE' by Spearman correlation test

SpearmanCorr corrP Q
CDKN1A|P21 0.6852 7.755e-08 1.49e-05
PIK3CA |PI3K-P110-ALPHA -0.5046 0.0002549 0.0245
RAF1|C-RAF -0.4172 0.003174 0.188
EIF4EBP1|4E-BP1_PT37_T46 0.4087 0.003923 0.188
Clinical variable #10: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  ESOPHAGUS ADENOCARCINOMA, NOS 48
  ESOPHAGUS SQUAMOUS CELL CARCINOMA 78
     
  Significant markers N = 30
  Higher in ESOPHAGUS SQUAMOUS CELL CARCINOMA 30
  Higher in ESOPHAGUS ADENOCARCINOMA, NOS 0
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Clinical variable #11: 'NUMBER_PACK_YEARS_SMOKED'

6 genes related to 'NUMBER_PACK_YEARS_SMOKED'.

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

NUMBER_PACK_YEARS_SMOKED Mean (SD) 36.39 (21)
  Significant markers N = 6
  pos. correlated 3
  neg. correlated 3
List of 6 genes differentially expressed by 'NUMBER_PACK_YEARS_SMOKED'

Table S17.  Get Full Table List of 6 genes significantly correlated to 'NUMBER_PACK_YEARS_SMOKED' by Spearman correlation test

SpearmanCorr corrP Q
CCNB1|CYCLIN_B1 -0.3691 0.002294 0.258
FASN|FASN -0.3443 0.004641 0.258
ACACA|ACC1 -0.3415 0.005015 0.258
KIT|C-KIT 0.3315 0.006548 0.258
BCL2L1|BCL-XL 0.3281 0.007163 0.258
RPTOR|RAPTOR 0.3236 0.008049 0.258
Clinical variable #12: 'RESIDUAL_TUMOR'

No gene related to 'RESIDUAL_TUMOR'.

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

RESIDUAL_TUMOR Labels N
  R0 101
  R1 10
  R2 1
  RX 7
     
  Significant markers N = 0
Clinical variable #13: 'NUMBER_OF_LYMPH_NODES'

No gene related to 'NUMBER_OF_LYMPH_NODES'.

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

NUMBER_OF_LYMPH_NODES Mean (SD) 2.18 (2.8)
  Significant markers N = 0
Clinical variable #14: 'RACE'

30 genes related to 'RACE'.

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

RACE Labels N
  ASIAN 43
  BLACK OR AFRICAN AMERICAN 2
  WHITE 73
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S21.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
PIK3CA |PI3K-P110-ALPHA 1.978e-08 3.8e-06
SRC|SRC_PY527 5.577e-08 5.35e-06
C12ORF5|TIGAR 7.605e-06 0.000487
G6PD|G6PD 1.46e-05 0.000701
FRAP1|MTOR_PS2448 2.143e-05 0.000823
CDKN1A|P21 0.0001927 0.00556
CCNE2|CYCLIN_E2 0.0002029 0.00556
PRDX1|PRDX1 0.0003242 0.00723
EIF4EBP1|4E-BP1_PT37_T46 0.0003387 0.00723
PKC|PKC-PAN_BETAII_PS660 0.000452 0.00792
Methods & Data
Input
  • Expresson data file = ESCA-TP.rppa.txt

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

  • Number of patients = 126

  • Number of genes = 192

  • 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, 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)