Correlation between gene methylation status and clinical features
Prostate Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
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/C1T72G7M
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 20041 genes and 13 clinical features across 265 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 9 clinical features related to at least one genes.

  • 38 genes correlated to 'AGE'.

    • NRN1 ,  AVPR1A ,  C17ORF104 ,  ZNF454 ,  OXT ,  ...

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

    • TACC2 ,  FAM13C ,  LDLRAD3 ,  XPNPEP1 ,  EPHX2 ,  ...

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

    • DLEU2__3 ,  SLC39A14 ,  C5ORF39

  • 3 genes correlated to 'NUMBER.OF.LYMPH.NODES'.

    • DLEU2__3 ,  SLC39A14 ,  C5ORF39

  • 148 genes correlated to 'GLEASON_SCORE_COMBINED'.

    • FAM13C ,  PKD1L3 ,  RRM2 ,  XPNPEP1 ,  EIF2C1 ,  ...

  • 312 genes correlated to 'GLEASON_SCORE_PRIMARY'.

    • RRM2 ,  FAM13C ,  HOXC4 ,  HOXC5 ,  HOXC6 ,  ...

  • 110 genes correlated to 'GLEASON_SCORE'.

    • FAM13C ,  PKD1L3 ,  RRM2 ,  DHX33 ,  MMP20 ,  ...

  • 50 genes correlated to 'PSA_RESULT_PREOP'.

    • FCRL2 ,  CD1B ,  MYCT1 ,  C6 ,  FCRL4 ,  ...

  • 2 genes correlated to 'PSA_VALUE'.

    • MIR30E ,  NFYC__1

  • No genes correlated to 'HISTOLOGICAL.TYPE', 'COMPLETENESS.OF.RESECTION', 'GLEASON_SCORE_SECONDARY', and 'RACE'.

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
AGE Spearman correlation test N=38 older N=38 younger N=0
PATHOLOGY T STAGE Spearman correlation test N=73 higher stage N=69 lower stage N=4
PATHOLOGY N STAGE Wilcoxon test N=3 class1 N=3 class0 N=0
HISTOLOGICAL TYPE Wilcoxon test   N=0        
COMPLETENESS OF RESECTION Kruskal-Wallis test   N=0        
NUMBER OF LYMPH NODES Spearman correlation test N=3 higher number.of.lymph.nodes N=1 lower number.of.lymph.nodes N=2
GLEASON_SCORE_COMBINED Spearman correlation test N=148 higher score N=91 lower score N=57
GLEASON_SCORE_PRIMARY Spearman correlation test N=312 higher score N=197 lower score N=115
GLEASON_SCORE_SECONDARY Spearman correlation test   N=0        
GLEASON_SCORE Spearman correlation test N=110 higher score N=57 lower score N=53
PSA_RESULT_PREOP Spearman correlation test N=50 higher psa_result_preop N=9 lower psa_result_preop N=41
PSA_VALUE Spearman correlation test N=2 higher psa_value N=2 lower psa_value N=0
RACE Kruskal-Wallis test   N=0        
Clinical variable #1: 'AGE'

38 genes related to 'AGE'.

Table S1.  Basic characteristics of clinical feature: 'AGE'

AGE Mean (SD) 60.24 (7)
  Significant markers N = 38
  pos. correlated 38
  neg. correlated 0
List of top 10 genes differentially expressed by 'AGE'

Table S2.  Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
NRN1 0.3417 1.383e-08 0.000277
AVPR1A 0.337 2.239e-08 0.000449
C17ORF104 0.3225 9.374e-08 0.00188
ZNF454 0.309 3.328e-07 0.00667
OXT 0.3065 4.202e-07 0.00842
TBX15 0.2991 8.137e-07 0.0163
PYDC1__1 0.2953 1.137e-06 0.0228
TRIM72__1 0.2953 1.137e-06 0.0228
INSC 0.2944 1.227e-06 0.0246
INA 0.2933 1.353e-06 0.0271
Clinical variable #2: 'PATHOLOGY.T.STAGE'

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

Table S3.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.55 (0.54)
  N
  2 123
  3 135
  4 5
     
  Significant markers N = 73
  pos. correlated 69
  neg. correlated 4
List of top 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S4.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
TACC2 0.3442 9.97e-09 2e-04
FAM13C 0.3425 1.19e-08 0.000238
LDLRAD3 0.3317 3.579e-08 0.000717
XPNPEP1 0.3294 4.485e-08 0.000899
EPHX2 0.3294 4.521e-08 0.000906
ARHGEF7 0.3265 5.985e-08 0.0012
EPN2 0.3224 8.941e-08 0.00179
CTNS__1 0.3199 1.133e-07 0.00227
ABCC10 0.3188 1.262e-07 0.00253
KBTBD11 0.318 1.366e-07 0.00274
Clinical variable #3: 'PATHOLOGY.N.STAGE'

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

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Labels N
  class0 194
  class1 24
     
  Significant markers N = 3
  Higher in class1 3
  Higher in class0 0
List of 3 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S6.  Get Full Table List of 3 genes differentially expressed by 'PATHOLOGY.N.STAGE'

W(pos if higher in 'class1') wilcoxontestP Q AUC
DLEU2__3 934 1.749e-06 0.0351 0.7994
SLC39A14 3605 1.192e-05 0.239 0.7743
C5ORF39 1065 1.484e-05 0.297 0.7713
Clinical variable #4: 'HISTOLOGICAL.TYPE'

No gene related to 'HISTOLOGICAL.TYPE'.

Table S7.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  PROSTATE ADENOCARCINOMA OTHER SUBTYPE 6
  PROSTATE ADENOCARCINOMA ACINAR TYPE 259
     
  Significant markers N = 0
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 188
  R1 56
  R2 2
  RX 6
     
  Significant markers N = 0
Clinical variable #6: 'NUMBER.OF.LYMPH.NODES'

3 genes related to 'NUMBER.OF.LYMPH.NODES'.

Table S9.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 0.25 (1.2)
  Significant markers N = 3
  pos. correlated 1
  neg. correlated 2
List of 3 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S10.  Get Full Table List of 3 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
DLEU2__3 -0.3287 7.787e-07 0.0156
SLC39A14 0.3038 5.439e-06 0.109
C5ORF39 -0.2978 8.496e-06 0.17
Clinical variable #7: 'GLEASON_SCORE_COMBINED'

148 genes related to 'GLEASON_SCORE_COMBINED'.

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

GLEASON_SCORE_COMBINED Mean (SD) 7.31 (0.82)
  Significant markers N = 148
  pos. correlated 91
  neg. correlated 57
List of top 10 genes differentially expressed by 'GLEASON_SCORE_COMBINED'

Table S12.  Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE_COMBINED' by Spearman correlation test

SpearmanCorr corrP Q
FAM13C 0.4121 2.762e-12 5.54e-08
PKD1L3 0.3799 1.586e-10 3.18e-06
RRM2 -0.3748 2.907e-10 5.83e-06
XPNPEP1 0.3745 3.006e-10 6.02e-06
EIF2C1 0.3715 4.263e-10 8.54e-06
FDFT1 0.3703 4.906e-10 9.83e-06
MMP20 0.3689 5.744e-10 1.15e-05
C15ORF21__1 0.3618 1.289e-09 2.58e-05
LIX1L 0.3574 2.102e-09 4.21e-05
ARHGEF7 0.3425 1.048e-08 0.00021
Clinical variable #8: 'GLEASON_SCORE_PRIMARY'

312 genes related to 'GLEASON_SCORE_PRIMARY'.

Table S13.  Basic characteristics of clinical feature: 'GLEASON_SCORE_PRIMARY'

GLEASON_SCORE_PRIMARY Mean (SD) 3.49 (0.57)
  Score N
  2 1
  3 142
  4 113
  5 9
     
  Significant markers N = 312
  pos. correlated 197
  neg. correlated 115
List of top 10 genes differentially expressed by 'GLEASON_SCORE_PRIMARY'

Table S14.  Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE_PRIMARY' by Spearman correlation test

SpearmanCorr corrP Q
RRM2 -0.4012 1.143e-11 2.29e-07
FAM13C 0.3839 9.866e-11 1.98e-06
HOXC4 -0.3762 2.479e-10 4.97e-06
HOXC5 -0.3762 2.479e-10 4.97e-06
HOXC6 -0.3762 2.479e-10 4.97e-06
EIF2C1 0.3731 3.565e-10 7.14e-06
CD38 0.3644 9.661e-10 1.94e-05
ARHGEF7 0.3602 1.54e-09 3.09e-05
OXT 0.3594 1.695e-09 3.39e-05
MEF2D 0.3545 2.9e-09 5.81e-05
Clinical variable #9: 'GLEASON_SCORE_SECONDARY'

No gene related to 'GLEASON_SCORE_SECONDARY'.

Table S15.  Basic characteristics of clinical feature: 'GLEASON_SCORE_SECONDARY'

GLEASON_SCORE_SECONDARY Mean (SD) 3.82 (0.63)
  Score N
  3 81
  4 152
  5 32
     
  Significant markers N = 0
Clinical variable #10: 'GLEASON_SCORE'

110 genes related to 'GLEASON_SCORE'.

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

GLEASON_SCORE Mean (SD) 7.34 (0.84)
  Score N
  6 21
  7 173
  8 32
  9 37
  10 2
     
  Significant markers N = 110
  pos. correlated 57
  neg. correlated 53
List of top 10 genes differentially expressed by 'GLEASON_SCORE'

Table S17.  Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE' by Spearman correlation test

SpearmanCorr corrP Q
FAM13C 0.404 7.93e-12 1.59e-07
PKD1L3 0.3798 1.606e-10 3.22e-06
RRM2 -0.3636 1.05e-09 2.1e-05
DHX33 0.3488 5.346e-09 0.000107
MMP20 0.3478 5.991e-09 0.00012
XPNPEP1 0.3437 9.192e-09 0.000184
DLEU2__3 -0.3427 1.026e-08 0.000206
FDFT1 0.3334 2.661e-08 0.000533
EIF2C1 0.3331 2.745e-08 0.00055
PLK1 -0.3317 3.187e-08 0.000638
Clinical variable #11: 'PSA_RESULT_PREOP'

50 genes related to 'PSA_RESULT_PREOP'.

Table S18.  Basic characteristics of clinical feature: 'PSA_RESULT_PREOP'

PSA_RESULT_PREOP Mean (SD) 10.29 (10)
  Significant markers N = 50
  pos. correlated 9
  neg. correlated 41
List of top 10 genes differentially expressed by 'PSA_RESULT_PREOP'

Table S19.  Get Full Table List of top 10 genes significantly correlated to 'PSA_RESULT_PREOP' by Spearman correlation test

SpearmanCorr corrP Q
FCRL2 -0.3833 1.244e-10 2.49e-06
CD1B -0.318 1.363e-07 0.00273
MYCT1 -0.3126 2.265e-07 0.00454
C6 -0.3111 2.608e-07 0.00523
FCRL4 -0.3053 4.461e-07 0.00894
LOC100124692 -0.3028 5.591e-07 0.0112
PGLYRP4 -0.3026 5.68e-07 0.0114
BACE2__1 0.3011 6.509e-07 0.013
FCRL3 -0.3005 6.858e-07 0.0137
C1ORF173 -0.2985 8.159e-07 0.0163
Clinical variable #12: 'PSA_VALUE'

2 genes related to 'PSA_VALUE'.

Table S20.  Basic characteristics of clinical feature: 'PSA_VALUE'

PSA_VALUE Mean (SD) 1.1 (3.9)
  Significant markers N = 2
  pos. correlated 2
  neg. correlated 0
List of 2 genes differentially expressed by 'PSA_VALUE'

Table S21.  Get Full Table List of 2 genes significantly correlated to 'PSA_VALUE' by Spearman correlation test

SpearmanCorr corrP Q
MIR30E 0.3303 5.065e-07 0.0102
NFYC__1 0.3303 5.065e-07 0.0102
Clinical variable #13: 'RACE'

No gene related to 'RACE'.

Table S22.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  ASIAN 2
  BLACK OR AFRICAN AMERICAN 7
  WHITE 147
     
  Significant markers N = 0
Methods & Data
Input
  • Expresson data file = PRAD-TP.meth.by_min_clin_corr.data.txt

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

  • Number of patients = 265

  • Number of genes = 20041

  • Number of clinical features = 13

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

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

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

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] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)
[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[3] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[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)