Correlation between gene methylation status and clinical features
Kidney Chromophobe (Primary solid tumor)
17 October 2014 | analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1N58K7W
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/C1N58K7W
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 19761 genes and 10 clinical features across 66 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 3 clinical features related to at least one genes.

- 1 gene correlated to 'PATHOLOGY.T.STAGE'.

- LRPAP1

- 2 genes correlated to 'GENDER'.

- ALG11__2 , UTP14C

- 4 genes correlated to 'NUMBERPACKYEARSSMOKED'.

- GRHL1 , LOC100133669 , LY6E , LOC729020

- No genes correlated to 'AGE', 'NEOPLASM.DISEASESTAGE', 'PATHOLOGY.N.STAGE', 'PATHOLOGY.M.STAGE', 'KARNOFSKY.PERFORMANCE.SCORE', 'RACE', and 'ETHNICITY'.

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 |
--- | --- | --- | --- | --- | --- | ---
AGE | Spearman correlation test | N=0 |  |  |  |
NEOPLASM DISEASESTAGE | Kruskal-Wallis test | N=0 |  |  |  |
PATHOLOGY T STAGE | Spearman correlation test | N=1 | higher stage | N=1 | lower stage | N=0
PATHOLOGY N STAGE | Spearman correlation test | N=0 |  |  |  |
PATHOLOGY M STAGE | Kruskal-Wallis test | N=0 |  |  |  |
GENDER | Wilcoxon test | N=2 | male | N=2 | female | N=0
KARNOFSKY PERFORMANCE SCORE | Spearman correlation test | N=0 |  |  |  |
NUMBERPACKYEARSSMOKED | Spearman correlation test | N=4 | higher numberpackyearssmoked | N=4 | lower numberpackyearssmoked | N=0
RACE | Kruskal-Wallis test | N=0 |  |  |  |
ETHNICITY | Wilcoxon test | N=0 |  |  |  |

Clinical variable #1: 'AGE'

No gene related to 'AGE'.

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

AGE | Mean (SD) | 51.52 (14)
| Significant markers | N = 0

Clinical variable #2: 'NEOPLASM.DISEASESTAGE'

No gene related to 'NEOPLASM.DISEASESTAGE'.

Table S2. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE | Labels | N
| STAGE I | 21
| STAGE II | 25
| STAGE III | 14
| STAGE IV | 6
| Significant markers | N = 0

Clinical variable #3: 'PATHOLOGY.T.STAGE'

One gene related to 'PATHOLOGY.T.STAGE'.

Table S3. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE | Mean (SD) | 2.02 (0.85)
|  | N
| 1 | 21
| 2 | 25
| 3 | 18
| 4 | 2
| Significant markers | N = 1
| pos. correlated | 1
| neg. correlated | 0

List of one gene differentially expressed by 'PATHOLOGY.T.STAGE'

Table S4. Get Full Table List of one gene significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
LRPAP1 | 0.5393 | 2.985e-06 | 0.059

Clinical variable #4: 'PATHOLOGY.N.STAGE'

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

Table S5. Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE | Mean (SD) | 0.16 (0.47)
|  | N
| 0 | 40
| 1 | 3
| 2 | 2
| Significant markers | N = 0

Clinical variable #5: 'PATHOLOGY.M.STAGE'

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

Table S6. Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE | Labels | N
| M0 | 34
| M1 | 2
| MX | 9
| Significant markers | N = 0

Clinical variable #6: 'GENDER'

2 genes related to 'GENDER'.

Table S7. Basic characteristics of clinical feature: 'GENDER'

GENDER | Labels | N
| FEMALE | 27
| MALE | 39
| Significant markers | N = 2
| Higher in MALE | 2
| Higher in FEMALE | 0

List of 2 genes differentially expressed by 'GENDER'

Table S8. Get Full Table List of 2 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__2 | 961 | 1.512e-08 | 0.000299 | 0.9126
UTP14C | 961 | 1.512e-08 | 0.000299 | 0.9126

Clinical variable #7: 'KARNOFSKY.PERFORMANCE.SCORE'

No gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S9. Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE | Mean (SD) | 89.09 (9.4)
| Score | N
| 70 | 1
| 80 | 2
| 90 | 5
| 100 | 3
| Significant markers | N = 0

Clinical variable #8: 'NUMBERPACKYEARSSMOKED'

4 genes related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED | Mean (SD) | 25.09 (22)
| Significant markers | N = 4
| pos. correlated | 4
| neg. correlated | 0

List of 4 genes differentially expressed by 'NUMBERPACKYEARSSMOKED'

Table S11. Get Full Table List of 4 genes significantly correlated to 'NUMBERPACKYEARSSMOKED' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
GRHL1 | 0.9704 | 7.42e-07 | 0.0147
LOC100133669 | 0.9658 | 1.403e-06 | 0.0277
LY6E | 0.9658 | 1.403e-06 | 0.0277
LOC729020 | 0.9431 | 1.353e-05 | 0.267

Clinical variable #9: 'RACE'

No gene related to 'RACE'.

Table S12. Basic characteristics of clinical feature: 'RACE'

RACE | Labels | N
| ASIAN | 2
| BLACK OR AFRICAN AMERICAN | 4
| WHITE | 58
| Significant markers | N = 0

Clinical variable #10: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S13. Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY | Labels | N
| HISPANIC OR LATINO | 4
| NOT HISPANIC OR LATINO | 32
| Significant markers | N = 0

Methods & Data
Input

- Expresson data file = KICH-TP.meth.by_min_clin_corr.data.txt

- Clinical data file = KICH-TP.merged_data.txt

- Number of patients = 66

- Number of genes = 19761

- Number of clinical features = 10

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.

- 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] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[3] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[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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