Correlation between mutation rate and clinical features
Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Correlation between mutation rate and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1KW5F68
Overview
Introduction

This pipeline uses various statistical tests to identify selected clinical features related to mutation rate.

Summary

Testing the association between 2 variables and 8 clinical features across 248 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 1 clinical feature related to at least one variables.

  • 2 variables correlated to 'HISTOLOGICAL_TYPE'.

    • MUTATIONRATE_SILENT ,  MUTATIONRATE_NONSYNONYMOUS

  • No variables correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'AGE', 'AGE_mutation.rate', 'RADIATIONS_RADIATION_REGIMENINDICATION', 'COMPLETENESS_OF_RESECTION', 'RACE', 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 variables that are significantly associated with each clinical feature at P value < 0.05 and Q value < 0.3.

Clinical feature Statistical test Significant variables Associated with                 Associated with
DAYS_TO_DEATH_OR_LAST_FUP Cox regression test   N=0        
AGE Spearman correlation test   N=0        
AGE Linear Regression Analysis   N=0        
HISTOLOGICAL_TYPE Kruskal-Wallis test N=2        
RADIATIONS_RADIATION_REGIMENINDICATION Wilcoxon test   N=0        
COMPLETENESS_OF_RESECTION Kruskal-Wallis test   N=0        
RACE Kruskal-Wallis test   N=0        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

No variable 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) 0.6-185.8 (median=29.9)
  censored N = 223
  death N = 24
     
  Significant variables N = 0
Clinical variable #2: 'AGE'

No variable related to 'AGE'.

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

AGE Mean (SD) 63.09 (11)
  Significant variables N = 0
Clinical variable #3: 'AGE'

No variable related to 'AGE'.

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

AGE Mean (SD) 63.09 (11)
  Significant variables N = 0
Clinical variable #4: 'HISTOLOGICAL_TYPE'

2 variables related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA 200
  MIXED SEROUS AND ENDOMETRIOID 4
  SEROUS ENDOMETRIAL ADENOCARCINOMA 44
     
  Significant variables N = 2
List of 2 variables associated with 'HISTOLOGICAL_TYPE'

Table S5.  Get Full Table List of 2 variables differentially expressed by 'HISTOLOGICAL_TYPE'

kruskal_wallis_P Q
MUTATIONRATE_SILENT 0.0001076 0.000215
MUTATIONRATE_NONSYNONYMOUS 0.005868 0.00587
Clinical variable #5: 'RADIATIONS_RADIATION_REGIMENINDICATION'

No variable related to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

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

RADIATIONS_RADIATION_REGIMENINDICATION Labels N
  NO 86
  YES 162
     
  Significant variables N = 0
Clinical variable #6: 'COMPLETENESS_OF_RESECTION'

No variable related to 'COMPLETENESS_OF_RESECTION'.

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

COMPLETENESS_OF_RESECTION Labels N
  R0 171
  R1 11
  R2 7
  RX 18
     
  Significant variables N = 0
Clinical variable #7: 'RACE'

No variable related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 3
  ASIAN 13
  BLACK OR AFRICAN AMERICAN 25
  NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 7
  WHITE 193
     
  Significant variables N = 0
Clinical variable #8: 'ETHNICITY'

No variable related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 4
  NOT HISPANIC OR LATINO 167
     
  Significant variables N = 0
Methods & Data
Input
  • Expresson data file = UCEC-TP.patients.counts_and_rates.txt

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

  • Number of patients = 248

  • Number of variables = 2

  • Number of clinical features = 8

Selected clinical features
  • For clinical features selected for this analysis and their value conozzle.versions, please find a documentation on selected CDEs .

  • 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)