Correlation between gene methylation status 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 gene methylation status and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1057F2Q
Overview
Introduction

This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.

Summary

Testing the association between 20333 genes and 7 clinical features across 420 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 'YEARS_TO_BIRTH'.

    • ANGPT4 ,  EPB41L1 ,  GPR158 ,  ITPK1 ,  NCRNA00203 ,  ...

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • APBB1IP ,  RASGRF1 ,  SSTR1 ,  KCNA5 ,  PPIH ,  ...

  • 30 genes correlated to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

    • GOLGA3 ,  ZNF831 ,  GUSBL2 ,  RMND5B ,  SAP130 ,  ...

  • 30 genes correlated to 'RACE'.

    • C18ORF54 ,  GNB2L1 ,  SNORD95 ,  GRAPL ,  LOC253039 ,  ...

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'COMPLETENESS_OF_RESECTION', 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=0        
YEARS_TO_BIRTH Spearman correlation test N=30 older N=6 younger N=24
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
RADIATIONS_RADIATION_REGIMENINDICATION Wilcoxon test N=30 yes N=30 no N=0
COMPLETENESS_OF_RESECTION Kruskal-Wallis test   N=0        
RACE Kruskal-Wallis test N=30        
ETHNICITY Wilcoxon test   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) 0.1-191.8 (median=19.4)
  censored N = 365
  death N = 54
     
  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) 64.22 (11)
  Significant markers N = 30
  pos. correlated 6
  neg. correlated 24
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
ANGPT4 0.3343 2.249e-12 4.57e-08
EPB41L1 -0.3289 5.292e-12 5.38e-08
GPR158 -0.3241 1.119e-11 7.59e-08
ITPK1 -0.3183 2.713e-11 1.1e-07
NCRNA00203 -0.3183 2.713e-11 1.1e-07
PLA2G15 -0.313 5.942e-11 2.01e-07
ALS2CL -0.3117 7.229e-11 2.1e-07
CACNB1 -0.3107 8.367e-11 2.13e-07
GRIN2B 0.3053 1.826e-10 4.13e-07
ADAMTS15 -0.3039 2.219e-10 4.51e-07
Clinical variable #3: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA 303
  MIXED SEROUS AND ENDOMETRIOID 20
  SEROUS ENDOMETRIAL ADENOCARCINOMA 97
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S5.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

kruskal_wallis_P Q
APBB1IP 4.698e-37 9.55e-33
RASGRF1 1.974e-32 1.23e-28
SSTR1 2.444e-32 1.23e-28
KCNA5 2.945e-32 1.23e-28
PPIH 3.019e-32 1.23e-28
ADAMTS16 5.609e-32 1.72e-28
LRRC36__1 5.915e-32 1.72e-28
ATP8A2 7.525e-32 1.91e-28
CARD11 9.23e-32 2.09e-28
CREB5 2.099e-31 4.27e-28
Clinical variable #4: 'RADIATIONS_RADIATION_REGIMENINDICATION'

30 genes related to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

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

RADIATIONS_RADIATION_REGIMENINDICATION Labels N
  NO 90
  YES 330
     
  Significant markers N = 30
  Higher in YES 30
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATIONS_RADIATION_REGIMENINDICATION'

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

W(pos if higher in 'YES') wilcoxontestP Q AUC
GOLGA3 21122 8.053e-10 1.64e-05 0.7112
ZNF831 20818 5.033e-09 4.56e-05 0.7009
GUSBL2 20728 8.517e-09 4.56e-05 0.6979
RMND5B 20719 8.973e-09 4.56e-05 0.6976
SAP130 20515 2.869e-08 0.000117 0.6907
MAP2K2 20447 4.191e-08 0.000134 0.6885
GIPR 20429 4.63e-08 0.000134 0.6878
KLHL9 20406 5.255e-08 0.000134 0.6871
C14ORF93 20316 8.59e-08 0.000193 0.684
WDR24 20298 9.468e-08 0.000193 0.6834
Clinical variable #5: 'COMPLETENESS_OF_RESECTION'

No gene related to 'COMPLETENESS_OF_RESECTION'.

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

COMPLETENESS_OF_RESECTION Labels N
  R0 277
  R1 19
  R2 13
  RX 34
     
  Significant markers N = 0
Clinical variable #6: 'RACE'

30 genes related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 2
  ASIAN 8
  BLACK OR AFRICAN AMERICAN 93
  NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 7
  WHITE 286
     
  Significant markers N = 30
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
C18ORF54 1.743e-18 3.54e-14
GNB2L1 4.138e-15 2.8e-11
SNORD95 4.138e-15 2.8e-11
GRAPL 7.979e-13 4.06e-09
LOC253039 2.418e-12 7.83e-09
PSMD5 2.418e-12 7.83e-09
NCRNA00174 2.697e-12 7.83e-09
CN5H6.4 1.042e-11 2.36e-08
GTSE1 1.042e-11 2.36e-08
GRAP 1.487e-11 3.02e-08
Clinical variable #7: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 11
  NOT HISPANIC OR LATINO 304
     
  Significant markers N = 0
Methods & Data
Input
  • Expresson data file = UCEC-TP.meth.by_min_clin_corr.data.txt

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

  • Number of patients = 420

  • Number of genes = 20333

  • Number of clinical features = 7

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)