Correlation between gene methylation status and clinical features
Stomach Adenocarcinoma (Primary solid tumor)
21 April 2013  |  analyses__2013_04_21
Maintainer Information
Citation Information
doi:10.7908/C1GX48JQ
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Stomach Adenocarcinoma (Primary solid tumor cohort) - 21 April 2013: Correlation between gene methylation status and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1GX48JQ
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 17280 genes and 11 clinical features across 102 samples, statistically thresholded by Q value < 0.05, 8 clinical features related to at least one genes.

  • 2 genes correlated to 'GENDER'.

    • KIF4B ,  UTP14C

  • 255 genes correlated to 'HISTOLOGICAL.TYPE'.

    • SNORA9 ,  PLD3 ,  KHDRBS1 ,  SERTAD1 ,  RNF44 ,  ...

  • 25 genes correlated to 'PATHOLOGY.T'.

    • ZNF296 ,  HSBP1L1 ,  RASSF6 ,  F11R ,  C19ORF33 ,  ...

  • 1 gene correlated to 'PATHOLOGICSPREAD(M)'.

    • HARS2

  • 1 gene correlated to 'TUMOR.STAGE'.

    • C8ORF80

  • 213 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • TSPAN1 ,  FSCN1 ,  VAMP8 ,  CPLX4 ,  GAL ,  ...

  • 50 genes correlated to 'COMPLETENESS.OF.RESECTION'.

    • LOC100128640 ,  KIAA1430 ,  ACVR1C ,  PARK2 ,  ZSCAN21 ,  ...

  • 1 gene correlated to 'NUMBER.OF.LYMPH.NODES'.

    • RPS6KB2

  • No genes correlated to 'Time to Death', 'AGE', and 'PATHOLOGY.N'.

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 Q value < 0.05.

Clinical feature Statistical test Significant genes Associated with                 Associated with
Time to Death Cox regression test   N=0        
AGE Spearman correlation test   N=0        
GENDER t test N=2 male N=1 female N=1
HISTOLOGICAL TYPE ANOVA test N=255        
PATHOLOGY T Spearman correlation test N=25 higher pT N=24 lower pT N=1
PATHOLOGY N Spearman correlation test   N=0        
PATHOLOGICSPREAD(M) ANOVA test N=1        
TUMOR STAGE Spearman correlation test N=1 higher stage N=1 lower stage N=0
RADIATIONS RADIATION REGIMENINDICATION t test N=213 yes N=196 no N=17
COMPLETENESS OF RESECTION ANOVA test N=50        
NUMBER OF LYMPH NODES Spearman correlation test N=1 higher number.of.lymph.nodes N=1 lower number.of.lymph.nodes 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 (Months) 0.1-72.2 (median=1.2)
  censored N = 83
  death N = 10
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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

AGE Mean (SD) 66.05 (11)
  Significant markers N = 0
Clinical variable #3: 'GENDER'

2 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 32
  MALE 70
     
  Significant markers N = 2
  Higher in MALE 1
  Higher in FEMALE 1
List of 2 genes differentially expressed by 'GENDER'

Table S4.  Get Full Table List of 2 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
KIF4B -13.16 1.205e-20 2.08e-16 0.9705
UTP14C 10.52 2.367e-13 4.09e-09 0.9482

Figure S1.  Get High-res Image As an example, this figure shows the association of KIF4B to 'GENDER'. P value = 1.21e-20 with T-test analysis.

Clinical variable #4: 'HISTOLOGICAL.TYPE'

255 genes related to 'HISTOLOGICAL.TYPE'.

Table S5.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  STOMACH ADENOCARCINOMA DIFFUSE TYPE 5
  STOMACH ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 6
  STOMACH INTESTINAL ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 4
  STOMACH INTESTINAL ADENOCARCINOMA  MUCINOUS TYPE 2
  STOMACH ADENOCARCINOMA - DIFFUSE TYPE 12
  STOMACH ADENOCARCINOMA - NOT OTHERWISE SPECIFIED (NOS) 42
  STOMACH INTESTINAL ADENOCARCINOMA - MUCINOUS TYPE 5
  STOMACH INTESTINAL ADENOCARCINOMA - PAPILLARY TYPE 3
  STOMACH INTESTINAL ADENOCARCINOMA - TUBULAR TYPE 9
  STOMACH INTESTINAL ADENOCARCINOMA - TYPE NOT OTHERWISE SPECIFIED (NOS) 14
     
  Significant markers N = 255
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S6.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
SNORA9 9.397e-31 1.62e-26
PLD3 7.763e-27 1.34e-22
KHDRBS1 2.581e-26 4.46e-22
SERTAD1 1.942e-25 3.35e-21
RNF44 5.289e-25 9.14e-21
FAM129B 4.012e-22 6.93e-18
SDHAF1 9.768e-20 1.69e-15
THAP9 1.209e-18 2.09e-14
SYT16 1.989e-18 3.44e-14
C19ORF52 2.926e-18 5.05e-14

Figure S2.  Get High-res Image As an example, this figure shows the association of SNORA9 to 'HISTOLOGICAL.TYPE'. P value = 9.4e-31 with ANOVA analysis.

Clinical variable #5: 'PATHOLOGY.T'

25 genes related to 'PATHOLOGY.T'.

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY.T'

PATHOLOGY.T Mean (SD) 2.6 (0.71)
  N
  T1 4
  T2 33
  T3 41
  T4 7
     
  Significant markers N = 25
  pos. correlated 24
  neg. correlated 1
List of top 10 genes significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

Table S8.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

SpearmanCorr corrP Q
ZNF296 0.5914 2.522e-09 4.36e-05
HSBP1L1 0.5665 1.59e-08 0.000275
RASSF6 0.537 1.171e-07 0.00202
F11R 0.5192 3.561e-07 0.00615
C19ORF33 0.5178 3.868e-07 0.00668
YIF1B 0.5178 3.868e-07 0.00668
GLB1L2 0.5136 4.977e-07 0.0086
BUB1B 0.5086 6.707e-07 0.0116
RAB26 0.5053 8.126e-07 0.014
CYB561 0.5048 8.363e-07 0.0144

Figure S3.  Get High-res Image As an example, this figure shows the association of ZNF296 to 'PATHOLOGY.T'. P value = 2.52e-09 with Spearman correlation analysis.

Clinical variable #6: 'PATHOLOGY.N'

No gene related to 'PATHOLOGY.N'.

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY.N'

PATHOLOGY.N Mean (SD) 1.02 (0.99)
  N
  N0 31
  N1 30
  N2 15
  N3 9
     
  Significant markers N = 0
Clinical variable #7: 'PATHOLOGICSPREAD(M)'

One gene related to 'PATHOLOGICSPREAD(M)'.

Table S10.  Basic characteristics of clinical feature: 'PATHOLOGICSPREAD(M)'

PATHOLOGICSPREAD(M) Labels N
  M0 73
  M1 7
  MX 5
     
  Significant markers N = 1
List of one gene differentially expressed by 'PATHOLOGICSPREAD(M)'

Table S11.  Get Full Table List of one gene differentially expressed by 'PATHOLOGICSPREAD(M)'

ANOVA_P Q
HARS2 8.868e-10 1.53e-05

Figure S4.  Get High-res Image As an example, this figure shows the association of HARS2 to 'PATHOLOGICSPREAD(M)'. P value = 8.87e-10 with ANOVA analysis.

Clinical variable #8: 'TUMOR.STAGE'

One gene related to 'TUMOR.STAGE'.

Table S12.  Basic characteristics of clinical feature: 'TUMOR.STAGE'

TUMOR.STAGE Mean (SD) 2.46 (0.96)
  N
  Stage 1 15
  Stage 2 29
  Stage 3 28
  Stage 4 13
     
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene significantly correlated to 'TUMOR.STAGE' by Spearman correlation test

Table S13.  Get Full Table List of one gene significantly correlated to 'TUMOR.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
C8ORF80 0.4973 1.285e-06 0.0222

Figure S5.  Get High-res Image As an example, this figure shows the association of C8ORF80 to 'TUMOR.STAGE'. P value = 1.28e-06 with Spearman correlation analysis.

Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

213 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

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

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 5
  YES 97
     
  Significant markers N = 213
  Higher in YES 196
  Higher in NO 17
List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S15.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
TSPAN1 13.01 6.144e-16 1.06e-11 0.9443
FSCN1 8.67 8.436e-14 1.46e-09 0.8165
VAMP8 8.56 2.676e-13 4.62e-09 0.7856
CPLX4 8.24 7.3e-13 1.26e-08 0.9155
GAL 8.06 1.757e-12 3.03e-08 0.7113
CBWD1 7.67 1.308e-11 2.26e-07 0.8577
MAFF 8.08 1.722e-11 2.98e-07 0.9278
ZNF609 7.53 2.439e-11 4.21e-07 0.8041
C1ORF74 7.91 3.912e-11 6.76e-07 0.8062
ATG7 7.65 5.263e-11 9.09e-07 0.901

Figure S6.  Get High-res Image As an example, this figure shows the association of TSPAN1 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 6.14e-16 with T-test analysis.

Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

50 genes related to 'COMPLETENESS.OF.RESECTION'.

Table S16.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 83
  R1 5
  R2 3
     
  Significant markers N = 50
List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S17.  Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
LOC100128640 2.206e-11 3.81e-07
KIAA1430 4.837e-10 8.36e-06
ACVR1C 7.899e-10 1.36e-05
PARK2 1.431e-09 2.47e-05
ZSCAN21 2.42e-09 4.18e-05
CEBPD 5.625e-09 9.72e-05
UACA 9.897e-09 0.000171
LOC150776 1.04e-08 0.00018
DENND5B 1.271e-08 0.000219
GPAA1 1.605e-08 0.000277

Figure S7.  Get High-res Image As an example, this figure shows the association of LOC100128640 to 'COMPLETENESS.OF.RESECTION'. P value = 2.21e-11 with ANOVA analysis.

Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

One gene related to 'NUMBER.OF.LYMPH.NODES'.

Table S18.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 4.47 (6.4)
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

Table S19.  Get Full Table List of one gene significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
RPS6KB2 0.4729 1.695e-06 0.0293

Figure S8.  Get High-res Image As an example, this figure shows the association of RPS6KB2 to 'NUMBER.OF.LYMPH.NODES'. P value = 1.69e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Methods & Data
Input

  • Expresson data file = STAD-TP.meth.for_correlation.filtered_data.txt

  • Clinical data file = STAD-TP.clin.merged.picked.txt

  • Number of patients = 102

  • Number of genes = 17280

  • 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

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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

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] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[4] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[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)
Copyright © 2013 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle