Correlation between RPPA expression and clinical features
Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)
23 September 2013  |  analyses__2013_09_23
Maintainer Information
Citation Information
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between RPPA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C10V8B53
Overview
Introduction

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

Summary

Testing the association between 166 genes and 5 clinical features across 200 samples, statistically thresholded by Q value < 0.05, 3 clinical features related to at least one genes.

  • 22 genes correlated to 'HISTOLOGICAL.TYPE'.

    • TP53|P53-R-V ,  AKT1 AKT2 AKT3|AKT_PS473-R-V ,  PGR|PR-R-V ,  CDH1|E-CADHERIN-R-V ,  ESR1|ER-ALPHA-R-V ,  ...

  • 1 gene correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • CHEK1|CHK1_PS345-R-C

  • 3 genes correlated to 'COMPLETENESS.OF.RESECTION'.

    • TP53|P53-R-V ,  ESR1|ER-ALPHA-R-V ,  BAK1|BAK-R-C

  • No genes correlated to 'Time to Death', and 'AGE'.

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 Q value < 0.05.

Clinical feature Statistical test Significant genes Associated with                 Associated with
Time to Death Cox regression test   N=0        
AGE Spearman correlation test   N=0        
HISTOLOGICAL TYPE ANOVA test N=22        
RADIATIONS RADIATION REGIMENINDICATION t test N=1 yes N=1 no N=0
COMPLETENESS OF RESECTION ANOVA test N=3        
Clinical variable #1: 'Time to Death'

No gene related to 'Time to Death'.

Table S1.  Basic characteristics of clinical feature: 'Time to Death'

Time to Death Duration (Months) 0.6-185.8 (median=28.9)
  censored N = 180
  death N = 20
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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

AGE Mean (SD) 62.73 (11)
  Significant markers N = 0
Clinical variable #3: 'HISTOLOGICAL.TYPE'

22 genes related to 'HISTOLOGICAL.TYPE'.

Table S3.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA 174
  MIXED SEROUS AND ENDOMETRIOID 3
  SEROUS ENDOMETRIAL ADENOCARCINOMA 23
     
  Significant markers N = 22
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S4.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
TP53|P53-R-V 3.531e-13 5.86e-11
AKT1 AKT2 AKT3|AKT_PS473-R-V 7.868e-09 1.3e-06
PGR|PR-R-V 1.195e-08 1.96e-06
CDH1|E-CADHERIN-R-V 1.945e-08 3.17e-06
ESR1|ER-ALPHA-R-V 2.978e-08 4.82e-06
CHEK2|CHK2_PT68-R-C 1.102e-07 1.77e-05
CDC2|CDK1-R-V 1.482e-07 2.37e-05
AKT1 AKT2 AKT3|AKT_PT308-R-V 1.476e-06 0.000235
ESR1|ER-ALPHA_PS118-R-V 3.174e-06 0.000501
PTEN|PTEN-R-V 5.508e-06 0.000865

Figure S1.  Get High-res Image As an example, this figure shows the association of TP53|P53-R-V to 'HISTOLOGICAL.TYPE'. P value = 3.53e-13 with ANOVA analysis.

Clinical variable #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

One gene related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S5.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 80
  YES 120
     
  Significant markers N = 1
  Higher in YES 1
  Higher in NO 0
List of one gene differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S6.  Get Full Table List of one gene differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
CHEK1|CHK1_PS345-R-C 3.69 0.0002956 0.0491 0.631

Figure S2.  Get High-res Image As an example, this figure shows the association of CHEK1|CHK1_PS345-R-C to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 0.000296 with T-test analysis.

Clinical variable #5: 'COMPLETENESS.OF.RESECTION'

3 genes related to 'COMPLETENESS.OF.RESECTION'.

Table S7.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 141
  R1 9
  R2 5
  RX 16
     
  Significant markers N = 3
List of 3 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S8.  Get Full Table List of 3 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
TP53|P53-R-V 2.677e-06 0.000444
ESR1|ER-ALPHA-R-V 0.0001445 0.0238
BAK1|BAK-R-C 0.0002593 0.0425

Figure S3.  Get High-res Image As an example, this figure shows the association of TP53|P53-R-V to 'COMPLETENESS.OF.RESECTION'. P value = 2.68e-06 with ANOVA analysis.

Methods & Data
Input
  • Expresson data file = UCEC-TP.rppa.txt

  • Clinical data file = UCEC-TP.clin.merged.picked.txt

  • Number of patients = 200

  • Number of genes = 166

  • Number of clinical features = 5

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

ANOVA analysis

For multi-class clinical features (ordinal or nominal), one-way analysis of variance (Howell 2002) was applied to compare the log2-expression levels between different clinical classes using 'anova' function in R

Student's t-test analysis

For two-class clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the log2-expression levels between the two clinical classes using 't.test' function in R

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] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[4] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[5] 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)