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.

- 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] 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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