Correlation between RPPA expression and clinical features
Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
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/C1MS3S24
Overview
Introduction

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

Summary

Testing the association between 208 genes and 7 clinical features across 437 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 4 clinical features related to at least one genes.

  • 30 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • CHEK2|CHK2_PT68 ,  ESR1|ER-ALPHA ,  VHL|VHL ,  PGR|PR ,  ERBB2|HER2_PY1248 ,  ...

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • RPS6KB1|P70S6K_PT389 ,  VHL|VHL ,  SHC1|SHC_PY317 ,  CCNE1|CYCLIN_E1 ,  ANXA1|ANNEXIN-1 ,  ...

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • TP53|P53 ,  AKT1 AKT2 AKT3|AKT_PS473 ,  AKT1 AKT2 AKT3|AKT_PT308 ,  CHEK2|CHK2_PT68 ,  ESR1|ER-ALPHA_PS118 ,  ...

  • 19 genes correlated to 'RACE'.

    • BID|BID ,  CDH2|N-CADHERIN ,  CDK1|CDK1 ,  YAP1|YAP_PS127 ,  MET|C-MET_PY1235 ,  ...

  • No genes correlated to 'RADIATION_THERAPY', 'RESIDUAL_TUMOR', 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=30 shorter survival N=16 longer survival N=14
YEARS_TO_BIRTH Spearman correlation test N=30 older N=14 younger N=16
RADIATION_THERAPY Wilcoxon test   N=0        
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
RESIDUAL_TUMOR Kruskal-Wallis test   N=0        
RACE Kruskal-Wallis test N=19        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

30 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) 0-185.8 (median=27.2)
  censored N = 367
  death N = 69
     
  Significant markers N = 30
  associated with shorter survival 16
  associated with longer survival 14
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

HazardRatio Wald_P Q C_index
CHEK2|CHK2_PT68 3.4 9.413e-06 0.002 0.63
ESR1|ER-ALPHA 0.72 3.335e-05 0.0035 0.333
VHL|VHL 1.38 0.0005982 0.033 0.596
PGR|PR 0.23 0.0006273 0.033 0.374
ERBB2|HER2_PY1248 1.63 0.0008067 0.034 0.538
ANXA1|ANNEXIN-1 0.64 0.001227 0.035 0.352
ESR1|ER-ALPHA_PS118 0.5 0.001353 0.035 0.362
MSH2|MSH2 2.6 0.001466 0.035 0.616
RPS6KA1|P90RSK 0.31 0.001539 0.035 0.359
AKT1 AKT2 AKT3|AKT_PT308 0.7 0.001691 0.035 0.404
Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 63.86 (11)
  Significant markers N = 30
  pos. correlated 14
  neg. correlated 16
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
RPS6KB1|P70S6K_PT389 0.2134 6.968e-06 0.000798
VHL|VHL 0.2124 7.672e-06 0.000798
SHC1|SHC_PY317 0.2036 1.841e-05 0.00128
CCNE1|CYCLIN_E1 0.1912 5.845e-05 0.00304
ANXA1|ANNEXIN-1 -0.1861 9.276e-05 0.00386
ARAF|A-RAF_PS299 0.1776 0.0001928 0.00669
MYH9|MYOSIN-IIA_PS1943 -0.1696 0.0003755 0.0112
NF2|NF2 -0.1672 0.0004558 0.0119
BAX|BAX -0.1595 0.0008281 0.0174
GATA6|GATA6 0.1652 0.0009126 0.0174
Clinical variable #3: 'RADIATION_THERAPY'

No gene related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 224
  YES 188
     
  Significant markers N = 0
Clinical variable #4: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA 326
  MIXED SEROUS AND ENDOMETRIOID 17
  SEROUS ENDOMETRIAL ADENOCARCINOMA 94
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

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

kruskal_wallis_P Q
TP53|P53 1.366e-21 2.84e-19
AKT1 AKT2 AKT3|AKT_PS473 5.214e-21 5.42e-19
AKT1 AKT2 AKT3|AKT_PT308 2.008e-20 1.39e-18
CHEK2|CHK2_PT68 1.115e-19 5.8e-18
ESR1|ER-ALPHA_PS118 2.365e-15 9.84e-14
CCNE1|CYCLIN_E1 1.306e-14 4.53e-13
PIK3CA |PI3K-P110-ALPHA 1.786e-14 5.31e-13
ESR1|ER-ALPHA 4.337e-14 1.13e-12
PTEN|PTEN 3.656e-10 8.45e-09
ANXA1|ANNEXIN-1 2.822e-09 5.87e-08
Clinical variable #5: 'RESIDUAL_TUMOR'

No gene related to 'RESIDUAL_TUMOR'.

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

RESIDUAL_TUMOR Labels N
  R0 301
  R1 14
  R2 11
  RX 34
     
  Significant markers N = 0
Clinical variable #6: 'RACE'

19 genes related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 3
  ASIAN 14
  BLACK OR AFRICAN AMERICAN 87
  NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 5
  WHITE 301
     
  Significant markers N = 19
List of top 10 genes differentially expressed by 'RACE'

Table S10.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
BID|BID 1.125e-05 0.00234
CDH2|N-CADHERIN 0.0001573 0.0164
CDK1|CDK1 0.001002 0.0695
YAP1|YAP_PS127 0.001495 0.0701
MET|C-MET_PY1235 0.001685 0.0701
ARID1A|ARID1A 0.003525 0.122
PDCD4|PDCD4 0.004406 0.131
EGFR|EGFR_PY1068 0.005642 0.136
BCL2L11|BIM 0.005875 0.136
ERBB3|HER3_PY1289 0.007737 0.161
Clinical variable #7: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 15
  NOT HISPANIC OR LATINO 295
     
  Significant markers N = 0
Methods & Data
Input
  • Expresson data file = UCEC-TP.rppa.txt

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

  • Number of patients = 437

  • Number of genes = 208

  • Number of clinical features = 7

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)