Correlation between gene methylation status and clinical features
Stomach Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C1CF9NXB
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/C1CF9NXB
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 19730 genes and 12 clinical features across 303 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 6 clinical features related to at least one genes.

  • 192 genes correlated to 'AGE'.

    • CDCA5 ,  ZFPL1 ,  TOP1MT ,  SPRR1A ,  SLC26A3 ,  ...

  • 207 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • TRNT1 ,  NIT1__1 ,  PFDN2__1 ,  MAP3K1 ,  CDK12 ,  ...

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

    • RPL24 ,  FAM3C ,  CEP152 ,  NBEAL2 ,  SPATA18 ,  ...

  • 5 genes correlated to 'GENDER'.

    • ALG11__1 ,  UTP14C ,  KIF4B ,  CDH15 ,  DDX43

  • 278 genes correlated to 'HISTOLOGICAL.TYPE'.

    • ASB14 ,  OVOL1 ,  C3ORF26 ,  FILIP1L ,  COX8C ,  ...

  • 418 genes correlated to 'RACE'.

    • GRAPL ,  CRYZ__1 ,  TYW3__1 ,  GTF2IRD2B ,  PYCRL ,  ...

  • No genes correlated to 'Time to Death', 'PATHOLOGY.N.STAGE', 'PATHOLOGY.M.STAGE', 'RADIATIONS.RADIATION.REGIMENINDICATION', 'COMPLETENESS.OF.RESECTION', and 'NUMBER.OF.LYMPH.NODES'.

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=192 older N=4 younger N=188
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=207        
PATHOLOGY T STAGE Spearman correlation test N=952 higher stage N=455 lower stage N=497
PATHOLOGY N STAGE Spearman correlation test   N=0        
PATHOLOGY M STAGE Kruskal-Wallis test   N=0        
GENDER Wilcoxon test N=5 male N=5 female N=0
HISTOLOGICAL TYPE Kruskal-Wallis test N=278        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test   N=0        
COMPLETENESS OF RESECTION Kruskal-Wallis test   N=0        
NUMBER OF LYMPH NODES Spearman correlation test   N=0        
RACE Kruskal-Wallis test N=418        
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) 0.1-122.3 (median=10.9)
  censored N = 212
  death N = 80
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

192 genes related to 'AGE'.

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

AGE Mean (SD) 65.54 (11)
  Significant markers N = 192
  pos. correlated 4
  neg. correlated 188
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
CDCA5 -0.322 1.445e-08 0.000285
ZFPL1 -0.322 1.445e-08 0.000285
TOP1MT -0.3183 2.143e-08 0.000423
SPRR1A -0.3108 4.737e-08 0.000934
SLC26A3 -0.3056 8.162e-08 0.00161
SLC12A7 -0.3052 8.494e-08 0.00168
KIAA1217 -0.3009 1.302e-07 0.00257
STARD10 -0.2998 1.463e-07 0.00289
DKFZP566F0947 -0.295 2.356e-07 0.00465
PRTN3 -0.2935 2.732e-07 0.00539
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

207 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 2
  STAGE IA 11
  STAGE IB 32
  STAGE II 25
  STAGE IIA 33
  STAGE IIB 46
  STAGE III 2
  STAGE IIIA 56
  STAGE IIIB 44
  STAGE IIIC 32
  STAGE IV 20
     
  Significant markers N = 207
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
TRNT1 9.004e-09 0.000178
NIT1__1 7.206e-08 0.00142
PFDN2__1 7.206e-08 0.00142
MAP3K1 7.52e-08 0.00148
CDK12 8.401e-08 0.00166
EED 9.565e-08 0.00189
SMAD1 1.054e-07 0.00208
MEGF9 1.102e-07 0.00217
MED22 1.194e-07 0.00235
RPL7A 1.194e-07 0.00235
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

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

PATHOLOGY.T.STAGE Mean (SD) 2.9 (0.85)
  N
  1 18
  2 71
  3 137
  4 77
     
  Significant markers N = 952
  pos. correlated 455
  neg. correlated 497
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
RPL24 -0.358 1.359e-10 2.68e-06
FAM3C -0.3576 1.436e-10 2.83e-06
CEP152 -0.3553 1.912e-10 3.77e-06
NBEAL2 0.3477 4.912e-10 9.69e-06
SPATA18 0.345 6.782e-10 1.34e-05
PIGY -0.3446 7.143e-10 1.41e-05
PVRL4 0.3389 1.41e-09 2.78e-05
SLC16A5 0.3375 1.66e-09 3.27e-05
C4ORF29 -0.3371 1.736e-09 3.42e-05
MFSD8 -0.3371 1.736e-09 3.42e-05
Clinical variable #5: 'PATHOLOGY.N.STAGE'

No gene related to 'PATHOLOGY.N.STAGE'.

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

PATHOLOGY.N.STAGE Mean (SD) 1.27 (1.1)
  N
  0 103
  1 76
  2 60
  3 63
     
  Significant markers N = 0
Clinical variable #6: 'PATHOLOGY.M.STAGE'

No gene related to 'PATHOLOGY.M.STAGE'.

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 274
  M1 14
  MX 15
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

5 genes related to 'GENDER'.

Table S10.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 118
  MALE 185
     
  Significant markers N = 5
  Higher in MALE 5
  Higher in FEMALE 0
List of 5 genes differentially expressed by 'GENDER'

Table S11.  Get Full Table List of 5 genes differentially expressed by 'GENDER'. 0 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
ALG11__1 20427 1.861e-37 3.67e-33 0.9357
UTP14C 20427 1.861e-37 3.67e-33 0.9357
KIF4B 3731 4.472e-22 8.82e-18 0.8291
CDH15 14594 7.556e-07 0.0149 0.6685
DDX43 7684 1.399e-05 0.276 0.648
Clinical variable #8: 'HISTOLOGICAL.TYPE'

278 genes related to 'HISTOLOGICAL.TYPE'.

Table S12.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  STOMACH ADENOCARCINOMA DIFFUSE TYPE 59
  STOMACH ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 126
  STOMACH INTESTINAL ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 45
  STOMACH INTESTINAL ADENOCARCINOMA TUBULAR TYPE 45
  STOMACH INTESTINAL ADENOCARCINOMA PAPILLARY TYPE 1
  STOMACH INTESTINAL ADENOCARCINOMA  MUCINOUS TYPE 18
  STOMACH INTESTINAL ADENOCARCINOMA  PAPILLARY TYPE 5
  STOMACH ADENOCARCINOMA SIGNET RING TYPE 4
     
  Significant markers N = 278
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S13.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
ASB14 2.215e-09 4.37e-05
OVOL1 1.004e-08 0.000198
C3ORF26 1.818e-08 0.000359
FILIP1L 1.818e-08 0.000359
COX8C 2.127e-08 0.000419
KIAA1409 2.127e-08 0.000419
SERPINB12 6.177e-08 0.00122
VIL1 6.282e-08 0.00124
NGEF 7.157e-08 0.00141
KRT23 7.807e-08 0.00154
Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

No gene related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S14.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 7
  YES 296
     
  Significant markers N = 0
Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

No gene related to 'COMPLETENESS.OF.RESECTION'.

Table S15.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 265
  R1 13
  R2 6
     
  Significant markers N = 0
Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

No gene related to 'NUMBER.OF.LYMPH.NODES'.

Table S16.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 5.06 (7.6)
  Significant markers N = 0
Clinical variable #12: 'RACE'

418 genes related to 'RACE'.

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

RACE Labels N
  ASIAN 86
  BLACK OR AFRICAN AMERICAN 4
  NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 1
  WHITE 185
     
  Significant markers N = 418
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
GRAPL 6.39e-14 1.26e-09
CRYZ__1 7.726e-11 1.52e-06
TYW3__1 7.726e-11 1.52e-06
GTF2IRD2B 1.119e-10 2.21e-06
PYCRL 6.07e-10 1.2e-05
C11ORF58 1.368e-09 2.7e-05
HIST1H4K 1.494e-09 2.95e-05
TRMT11 1.579e-09 3.11e-05
LOC100271836 2.572e-09 5.07e-05
PIGY 6.779e-09 0.000134
Methods & Data
Input

  • Expresson data file = STAD-TP.meth.by_min_clin_corr.data.txt

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

  • Number of patients = 303

  • Number of genes = 19730

  • Number of clinical features = 12

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)
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