Correlation between gene methylation status and clinical features
Pancreatic Adenocarcinoma (Primary solid tumor)
23 May 2013  |  analyses__2013_05_23
Maintainer Information
Citation Information
doi:10.7908/C11J97TZ
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between gene methylation status and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C11J97TZ
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 20596 genes and 8 clinical features across 23 samples, statistically thresholded by Q value < 0.05, 6 clinical features related to at least one genes.

  • 3 genes correlated to 'GENDER'.

    • ALG11__1 ,  UTP14C ,  KIF4B

  • 5 genes correlated to 'HISTOLOGICAL.TYPE'.

    • ME1 ,  FGFR1OP ,  ZNF552 ,  RBP7 ,  SPAG8

  • 14 genes correlated to 'DISTANT.METASTASIS'.

    • RAB21 ,  SETD6 ,  FAM38A ,  TTC12 ,  NTN3 ,  ...

  • 15 genes correlated to 'LYMPH.NODE.METASTASIS'.

    • C1ORF88 ,  CCND2 ,  HNRNPA3 ,  ANKRD13D ,  DYRK1B ,  ...

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

    • C14ORF73 ,  HAAO ,  BEGAIN ,  GRID1 ,  ARMC4 ,  ...

  • 37 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • ATP6V0E2 ,  LOC401431 ,  LOC652276 ,  HES4 ,  C4ORF48 ,  ...

  • No genes correlated to 'AGE', 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 Q value < 0.05.

Clinical feature Statistical test Significant genes Associated with                 Associated with
AGE Spearman correlation test   N=0        
GENDER t test N=3 male N=2 female N=1
HISTOLOGICAL TYPE ANOVA test N=5        
DISTANT METASTASIS ANOVA test N=14        
LYMPH NODE METASTASIS ANOVA test N=15        
COMPLETENESS OF RESECTION ANOVA test N=79        
NUMBER OF LYMPH NODES Spearman correlation test   N=0        
NEOPLASM DISEASESTAGE ANOVA test N=37        
Clinical variable #1: 'AGE'

No gene related to 'AGE'.

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

AGE Mean (SD) 67.13 (8.6)
  Significant markers N = 0
Clinical variable #2: 'GENDER'

3 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 11
  MALE 12
     
  Significant markers N = 3
  Higher in MALE 2
  Higher in FEMALE 1
List of 3 genes differentially expressed by 'GENDER'

Table S3.  Get Full Table List of 3 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
ALG11__1 6.83 1.2e-06 0.0247 0.9697
UTP14C 6.83 1.2e-06 0.0247 0.9697
KIF4B -6.84 1.822e-06 0.0375 0.9924

Figure S1.  Get High-res Image As an example, this figure shows the association of ALG11__1 to 'GENDER'. P value = 1.2e-06 with T-test analysis.

Clinical variable #3: 'HISTOLOGICAL.TYPE'

5 genes related to 'HISTOLOGICAL.TYPE'.

Table S4.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  PANCREAS-ADENOCARCINOMA DUCTAL TYPE 20
  PANCREAS-ADENOCARCINOMA-OTHER SUBTYPE 2
  PANCREAS-COLLOID (MUCINOUS NON-CYSTIC) CARCINOMA 1
     
  Significant markers N = 5
List of 5 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S5.  Get Full Table List of 5 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
ME1 8.002e-19 1.65e-14
FGFR1OP 1.005e-14 2.07e-10
ZNF552 3.778e-12 7.78e-08
RBP7 4.832e-12 9.95e-08
SPAG8 1.601e-09 3.3e-05

Figure S2.  Get High-res Image As an example, this figure shows the association of ME1 to 'HISTOLOGICAL.TYPE'. P value = 8e-19 with ANOVA analysis.

Clinical variable #4: 'DISTANT.METASTASIS'

14 genes related to 'DISTANT.METASTASIS'.

Table S6.  Basic characteristics of clinical feature: 'DISTANT.METASTASIS'

DISTANT.METASTASIS Labels N
  M0 2
  M1 1
  MX 20
     
  Significant markers N = 14
List of top 10 genes differentially expressed by 'DISTANT.METASTASIS'

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

ANOVA_P Q
RAB21 1.035e-16 2.13e-12
SETD6 4.233e-14 8.72e-10
FAM38A 5.286e-13 1.09e-08
TTC12 7.391e-12 1.52e-07
NTN3 1.471e-09 3.03e-05
TRIM4 1.616e-08 0.000333
SLCO4C1 6.074e-08 0.00125
GUSB 6.242e-08 0.00129
KATNAL2__1 8.655e-08 0.00178
TCEB3B 8.655e-08 0.00178

Figure S3.  Get High-res Image As an example, this figure shows the association of RAB21 to 'DISTANT.METASTASIS'. P value = 1.04e-16 with ANOVA analysis.

Clinical variable #5: 'LYMPH.NODE.METASTASIS'

15 genes related to 'LYMPH.NODE.METASTASIS'.

Table S8.  Basic characteristics of clinical feature: 'LYMPH.NODE.METASTASIS'

LYMPH.NODE.METASTASIS Labels N
  N0 8
  N1 14
  N1B 1
     
  Significant markers N = 15
List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

Table S9.  Get Full Table List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

ANOVA_P Q
C1ORF88 2.575e-13 5.3e-09
CCND2 7.452e-12 1.53e-07
HNRNPA3 1.111e-10 2.29e-06
ANKRD13D 3.241e-09 6.67e-05
DYRK1B 5.755e-09 0.000119
SORT1 1.501e-08 0.000309
LHFPL5 7.133e-08 0.00147
ZNF655 2.358e-07 0.00486
BASP1__1 2.736e-07 0.00563
IFNAR1 4.618e-07 0.00951

Figure S4.  Get High-res Image As an example, this figure shows the association of C1ORF88 to 'LYMPH.NODE.METASTASIS'. P value = 2.58e-13 with ANOVA analysis.

Clinical variable #6: 'COMPLETENESS.OF.RESECTION'

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

Table S10.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 13
  R1 9
  RX 1
     
  Significant markers N = 79
List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S11.  Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
C14ORF73 7.086e-30 1.46e-25
HAAO 5.254e-23 1.08e-18
BEGAIN 7.541e-19 1.55e-14
GRID1 1.117e-18 2.3e-14
ARMC4 1.231e-17 2.53e-13
LASS3 2.305e-17 4.75e-13
ZNF230 1.349e-16 2.78e-12
GPATCH2__1 1.632e-16 3.36e-12
SPATA17__1 1.632e-16 3.36e-12
C5ORF42 9.036e-16 1.86e-11

Figure S5.  Get High-res Image As an example, this figure shows the association of C14ORF73 to 'COMPLETENESS.OF.RESECTION'. P value = 7.09e-30 with ANOVA analysis.

Clinical variable #7: 'NUMBER.OF.LYMPH.NODES'

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

Table S12.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.22 (2.7)
  Significant markers N = 0
Clinical variable #8: 'NEOPLASM.DISEASESTAGE'

37 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S13.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE IA 2
  STAGE IB 1
  STAGE IIA 3
  STAGE IIB 15
  STAGE III 1
  STAGE IV 1
     
  Significant markers N = 37
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S14.  Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
ATP6V0E2 4.35e-27 8.96e-23
LOC401431 4.35e-27 8.96e-23
LOC652276 6.025e-26 1.24e-21
HES4 1.042e-22 2.15e-18
C4ORF48 5.243e-20 1.08e-15
SCHIP1 1.432e-18 2.95e-14
RAB21 1.795e-13 3.7e-09
TAS2R3 5.627e-11 1.16e-06
SETD6 6.312e-11 1.3e-06
C1ORF104__1 1.758e-10 3.62e-06

Figure S6.  Get High-res Image As an example, this figure shows the association of ATP6V0E2 to 'NEOPLASM.DISEASESTAGE'. P value = 4.35e-27 with ANOVA analysis.

Methods & Data
Input

  • Expresson data file = PAAD-TP.meth.by_min_expr_corr.data.txt

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

  • Number of patients = 23

  • Number of genes = 20596

  • Number of clinical features = 8

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] 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)
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