Correlation between gene methylation status and clinical features
Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between gene methylation status and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1JW8CSW
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 19831 genes and 11 clinical features across 206 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 8 clinical features related to at least one genes.

  • 18 genes correlated to 'AGE'.

    • ELOVL2 ,  ARHGAP1 ,  TNFAIP6 ,  CTSD ,  HCCA2__4 ,  ...

  • 529 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • DLX6 ,  DLX6AS ,  DLEU2 ,  TMEM132B ,  DIDO1 ,  ...

  • 883 genes correlated to 'PATHOLOGY.T.STAGE'.

    • DLX6 ,  DLX6AS ,  DIDO1 ,  GPR150 ,  NSD1 ,  ...

  • 40 genes correlated to 'PATHOLOGY.N.STAGE'.

    • KLK7 ,  FOXF1 ,  LBXCOR1 ,  MEOX2 ,  HOXA13 ,  ...

  • 76 genes correlated to 'PATHOLOGY.M.STAGE'.

    • CHD1 ,  ZNF18 ,  DSCR9 ,  ZNF222 ,  ZNF132 ,  ...

  • 65 genes correlated to 'GENDER'.

    • ALG11__2 ,  UTP14C ,  PRKRIR ,  MYST2 ,  WBP11P1 ,  ...

  • 20 genes correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

    • CHAF1B ,  ZNF610 ,  DOK6 ,  AOC3 ,  NPHP4 ,  ...

  • 21 genes correlated to 'RACE'.

    • DHRS7 ,  SCAMP5 ,  DARC ,  RCBTB2 ,  C14ORF167 ,  ...

  • No genes correlated to 'Time to Death', 'NUMBERPACKYEARSSMOKED', 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
Time to Death Cox regression test   N=0        
AGE Spearman correlation test N=18 older N=8 younger N=10
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=529        
PATHOLOGY T STAGE Spearman correlation test N=883 higher stage N=680 lower stage N=203
PATHOLOGY N STAGE Spearman correlation test N=40 higher stage N=40 lower stage N=0
PATHOLOGY M STAGE Kruskal-Wallis test N=76        
GENDER Wilcoxon test N=65 male N=65 female N=0
KARNOFSKY PERFORMANCE SCORE Spearman correlation test N=20 higher score N=15 lower score N=5
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
RACE Kruskal-Wallis test N=21        
ETHNICITY Wilcoxon test   N=0        
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 (Years) 2-5925 (median=510.5)
  censored N = 174
  death N = 6
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

18 genes related to 'AGE'.

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

AGE Mean (SD) 60.78 (12)
  Significant markers N = 18
  pos. correlated 8
  neg. correlated 10
List of top 10 genes differentially expressed by 'AGE'

Table S3.  Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
ELOVL2 0.3761 3.473e-08 0.000689
ARHGAP1 -0.368 7.09e-08 0.00141
TNFAIP6 0.356 1.999e-07 0.00396
CTSD -0.3356 1.05e-06 0.0208
HCCA2__4 -0.3356 1.05e-06 0.0208
ATP6V0C -0.3309 1.508e-06 0.0299
ARGFXP2 -0.3238 2.584e-06 0.0512
RHOT1 -0.3238 2.584e-06 0.0512
SLCO2A1 0.3209 3.221e-06 0.0639
AAK1 -0.3113 6.519e-06 0.129
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

529 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S4.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 133
  STAGE II 13
  STAGE III 42
  STAGE IV 12
     
  Significant markers N = 529
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

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

ANOVA_P Q
DLX6 2.286e-11 4.53e-07
DLX6AS 2.286e-11 4.53e-07
DLEU2 6.724e-11 1.33e-06
TMEM132B 1.165e-10 2.31e-06
DIDO1 1.277e-10 2.53e-06
NSD1 1.511e-10 3e-06
FLOT2 4.598e-10 9.11e-06
LBXCOR1 6.57e-10 1.3e-05
POU6F2 7.42e-10 1.47e-05
CCNI2 1.365e-09 2.71e-05
Clinical variable #4: 'PATHOLOGY.T.STAGE'

883 genes related to 'PATHOLOGY.T.STAGE'.

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 1.56 (0.88)
  N
  1 140
  2 15
  3 47
  4 2
     
  Significant markers N = 883
  pos. correlated 680
  neg. correlated 203
List of top 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S7.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
DLX6 0.4963 4.405e-14 8.74e-10
DLX6AS 0.4963 4.405e-14 8.74e-10
DIDO1 0.4912 8.717e-14 1.73e-09
GPR150 0.465 2.438e-12 4.83e-08
NSD1 0.4646 2.566e-12 5.09e-08
ZNF154 0.4617 3.632e-12 7.2e-08
FLOT2 0.4616 3.671e-12 7.28e-08
C6ORF195 0.4553 7.821e-12 1.55e-07
CCNI2 0.4542 8.862e-12 1.76e-07
TBX4 0.452 1.153e-11 2.29e-07
Clinical variable #5: 'PATHOLOGY.N.STAGE'

40 genes related to 'PATHOLOGY.N.STAGE'.

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.45 (0.62)
  N
  0 37
  1 19
  2 4
     
  Significant markers N = 40
  pos. correlated 40
  neg. correlated 0
List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S9.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
KLK7 0.6367 4.535e-08 0.000899
FOXF1 0.6145 1.767e-07 0.0035
LBXCOR1 0.6091 2.408e-07 0.00478
MEOX2 0.6009 3.848e-07 0.00763
HOXA13 0.5976 4.628e-07 0.00918
ZNF702P 0.595 5.331e-07 0.0106
PLEKHF2 0.5946 5.476e-07 0.0109
DCC 0.5895 7.224e-07 0.0143
NAGS 0.586 8.718e-07 0.0173
PYY 0.586 8.718e-07 0.0173
Clinical variable #6: 'PATHOLOGY.M.STAGE'

76 genes related to 'PATHOLOGY.M.STAGE'.

Table S10.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 79
  M1 7
  MX 112
     
  Significant markers N = 76
List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S11.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
CHD1 4.093e-08 0.000812
ZNF18 7.495e-07 0.0149
DSCR9 7.677e-07 0.0152
ZNF222 8.441e-07 0.0167
ZNF132 1.042e-06 0.0207
SLCO5A1 1.354e-06 0.0268
MMP28 1.509e-06 0.0299
MYOT 1.689e-06 0.0335
C22ORF26__1 1.719e-06 0.0341
LOC150381__1 1.719e-06 0.0341
Clinical variable #7: 'GENDER'

65 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 59
  MALE 147
     
  Significant markers N = 65
  Higher in MALE 65
  Higher in FEMALE 0
List of top 10 genes differentially expressed by 'GENDER'

Table S13.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'. 1 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
ALG11__2 7930 1.555e-20 3.08e-16 0.9143
UTP14C 7930 1.555e-20 3.08e-16 0.9143
PRKRIR 7740 1.393e-18 2.76e-14 0.8924
MYST2 7434 1.177e-15 2.33e-11 0.8571
WBP11P1 7340 8.24e-15 1.63e-10 0.8463
FKBP5 1785 4.245e-11 8.42e-07 0.7942
PEMT 1813 6.898e-11 1.37e-06 0.791
NARFL 1846 1.214e-10 2.41e-06 0.7872
C5ORF27 1875 1.984e-10 3.93e-06 0.7838
AOX1 1929 4.879e-10 9.67e-06 0.7776
Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

20 genes related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S14.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 93.39 (10)
  Score N
  40 1
  70 1
  80 4
  90 20
  100 30
     
  Significant markers N = 20
  pos. correlated 15
  neg. correlated 5
List of top 10 genes differentially expressed by 'KARNOFSKY.PERFORMANCE.SCORE'

Table S15.  Get Full Table List of top 10 genes significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

SpearmanCorr corrP Q
CHAF1B 0.5919 1.548e-06 0.0307
ZNF610 -0.5864 2.045e-06 0.0406
DOK6 -0.5862 2.069e-06 0.041
AOC3 0.5847 2.219e-06 0.044
NPHP4 -0.5816 2.595e-06 0.0514
GDPD5 0.5774 3.183e-06 0.0631
APOBEC3H 0.577 3.249e-06 0.0644
FAM38A 0.5758 3.439e-06 0.0682
SCARF1 0.5737 3.797e-06 0.0753
ZNF785 -0.5632 6.217e-06 0.123
Clinical variable #9: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 32.68 (34)
  Significant markers N = 0
Clinical variable #10: 'RACE'

21 genes related to 'RACE'.

Table S17.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 2
  ASIAN 5
  BLACK OR AFRICAN AMERICAN 45
  WHITE 139
     
  Significant markers N = 21
List of top 10 genes differentially expressed by 'RACE'

Table S18.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

ANOVA_P Q
DHRS7 4.399e-14 8.72e-10
SCAMP5 1.715e-11 3.4e-07
DARC 3.246e-09 6.44e-05
RCBTB2 3.271e-09 6.49e-05
C14ORF167 2.311e-07 0.00458
DHRS4 2.311e-07 0.00458
MIR320A 3.262e-07 0.00647
POLR3D 3.262e-07 0.00647
RABL2A 5.126e-07 0.0102
RPL23AP7 5.126e-07 0.0102
Clinical variable #11: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 9
  NOT HISPANIC OR LATINO 160
     
  Significant markers N = 0
Methods & Data
Input
  • Expresson data file = KIRP-TP.meth.by_min_clin_corr.data.txt

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

  • Number of patients = 206

  • Number of genes = 19831

  • Number of clinical features = 11

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)