Prostate Adenocarcinoma: Correlation between gene methylation status and clinical features
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 17263 genes and 3 clinical features across 50 samples, statistically thresholded by Q value < 0.05, 2 clinical features related to at least one genes.

- 9 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

- SCD , ZNF473 , PFDN5 , RNMTL1 , ZNF506 , ...

- 163 genes correlated to 'NEOADJUVANT.THERAPY'.

- LOC100130581 , GNG7 , CLDN23 , HOTAIR , TMEM38A , ...

- No genes correlated to 'AGE'

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 |  |  |  |
RADIATIONS RADIATION REGIMENINDICATION | t test | N=9 | yes | N=6 | no | N=3
NEOADJUVANT THERAPY | t test | N=163 | yes | N=100 | no | N=63

Clinical variable #1: 'AGE'

No gene related to 'AGE'.

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

AGE | Mean (SD) | 60.78 (7)
| Significant markers | N = 0

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

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

Table S2. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N
| NO | 4
| YES | 46
| Significant markers | N = 9
| Higher in YES | 6
| Higher in NO | 3

List of 9 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S3. Get Full Table List of 9 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

| T(pos if higher in 'YES') | ttestP | Q | AUC
--- | --- | --- | --- | ---
SCD | -7.29 | 3.335e-09 | 5.76e-05 | 0.8859
ZNF473 | 6.26 | 2.126e-07 | 0.00367 | 0.8315
PFDN5 | 5.72 | 7.899e-07 | 0.0136 | 0.8696
RNMTL1 | -5.84 | 8.66e-07 | 0.0149 | 0.8098
ZNF506 | 5.79 | 1.572e-06 | 0.0271 | 0.8152
POLD3 | 6.11 | 1.84e-06 | 0.0317 | 0.8478
C8ORF42 | 5.98 | 2.142e-06 | 0.037 | 0.9022
TC2N | -5.38 | 2.226e-06 | 0.0384 | 0.8207
WIBG | 5.49 | 2.808e-06 | 0.0485 | 0.7717

Figure S1. Get High-res Image As an example, this figure shows the association of SCD to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 3.34e-09 with T-test analysis.

Clinical variable #3: 'NEOADJUVANT.THERAPY'

163 genes related to 'NEOADJUVANT.THERAPY'.

Table S4. Basic characteristics of clinical feature: 'NEOADJUVANT.THERAPY'

NEOADJUVANT.THERAPY | Labels | N
| NO | 3
| YES | 47
| Significant markers | N = 163
| Higher in YES | 100
| Higher in NO | 63

List of top 10 genes differentially expressed by 'NEOADJUVANT.THERAPY'

Table S5. Get Full Table List of top 10 genes differentially expressed by 'NEOADJUVANT.THERAPY'

| T(pos if higher in 'YES') | ttestP | Q | AUC
--- | --- | --- | --- | ---
LOC100130581 | 10.17 | 3.106e-13 | 5.36e-09 | 0.9858
GNG7 | -12.87 | 3.239e-13 | 5.59e-09 | 0.9574
CLDN23 | 9.74 | 7.017e-13 | 1.21e-08 | 0.9787
HOTAIR | 9.73 | 8.4e-13 | 1.45e-08 | 0.9574
TMEM38A | 9.53 | 1.265e-12 | 2.18e-08 | 0.9362
SLC44A2 | -9.43 | 1.775e-12 | 3.06e-08 | 0.8865
CYP17A1 | 9.42 | 3.936e-12 | 6.79e-08 | 0.9787
ANGPTL2 | -9.15 | 4.922e-12 | 8.49e-08 | 0.9291
C21ORF56 | 9.2 | 5.13e-12 | 8.85e-08 | 0.8723
ALOX5 | -10.86 | 6.036e-12 | 1.04e-07 | 0.9787

Figure S2. Get High-res Image As an example, this figure shows the association of LOC100130581 to 'NEOADJUVANT.THERAPY'. P value = 3.11e-13 with T-test analysis.

Methods & Data
Input

- Expresson data file = PRAD.meth.for_correlation.filtered_data.txt

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

- Number of patients = 50

- Number of genes = 17263

- Number of clinical features = 3

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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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)
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