Prostate Adenocarcinoma: Correlation between gene methylation status and clinical features
(primary solid tumor cohort)
Maintained by Juok Cho (Broad Institute)
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 17323 genes and 2 clinical features across 114 samples, statistically thresholded by Q value < 0.05, 2 clinical features related to at least one genes.

  • 2 genes correlated to 'AGE'.

    • CACNA1B ,  RASGRF1

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

    • NAA20 ,  ZNF280D ,  SCD ,  HIST1H2BB ,  ZKSCAN4 ,  ...

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=2 older N=2 younger N=0
RADIATIONS RADIATION REGIMENINDICATION t test N=54 yes N=42 no N=12
Clinical variable #1: 'AGE'

2 genes related to 'AGE'.

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

AGE Mean (SD) 60.44 (7.1)
  Significant markers N = 2
  pos. correlated 2
  neg. correlated 0
List of 2 genes significantly correlated to 'AGE' by Spearman correlation test

Table S2.  Get Full Table List of 2 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
CACNA1B 0.4795 6.731e-08 0.00117
RASGRF1 0.4381 1.089e-06 0.0189

Figure S1.  Get High-res Image As an example, this figure shows the association of CACNA1B to 'AGE'. P value = 6.73e-08 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #2: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S3.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 5
  YES 109
     
  Significant markers N = 54
  Higher in YES 42
  Higher in NO 12
List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S4.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
NAA20 9.34 2.343e-14 4.06e-10 0.8606
ZNF280D 9.24 1.219e-13 2.11e-09 0.7963
SCD -8.93 2.37e-12 4.1e-08 0.8385
HIST1H2BB 7.7 6.301e-12 1.09e-07 0.7174
ZKSCAN4 9.27 2.297e-11 3.98e-07 0.8606
CLEC4C -7.34 6.21e-11 1.08e-06 0.7596
AASDHPPT 7.41 7.077e-11 1.23e-06 0.8569
ZNF525 9.23 1.761e-10 3.05e-06 0.8826
VWDE 6.83 4.661e-10 8.07e-06 0.7725
PIK3CA 6.82 7.493e-09 0.00013 0.7908

Figure S2.  Get High-res Image As an example, this figure shows the association of NAA20 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 2.34e-14 with T-test analysis.

Methods & Data
Input
  • Expresson data file = PRAD-TP.meth.for_correlation.filtered_data.txt

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

  • Number of patients = 114

  • Number of genes = 17323

  • Number of clinical features = 2

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

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] 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)