Thyroid Adenocarcinoma: Correlation between mRNAseq expression and clinical features
Maintained by Juok Cho (Broad Institute)
Overview
Introduction

This pipeline uses various statistical tests to identify mRNAs whose expression levels correlated to selected clinical features.

Summary

Testing the association between 17972 genes and 5 clinical features across 173 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

- 35 genes correlated to 'AGE'.

- CD97|976 , C12ORF52|84934 , KBTBD2|25948 , GPR173|54328 , GOT2|2806 , ...

- 35 genes correlated to 'GENDER'.

- DDX3Y|8653 , RPS4Y1|6192 , ZFY|7544 , USP9Y|8287 , UTY|7404 , ...

- 3273 genes correlated to 'HISTOLOGICAL.TYPE'.

- ANKLE2|23141 , FN1|2335 , LDLR|3949 , FAM176A|84141 , TMPRSS6|164656 , ...

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

- FLJ37543|285668 , C14ORF180|400258 , A2ML1|144568 , DNAH14|127602 , LOC440173|440173 , ...

- 137 genes correlated to 'NEOADJUVANT.THERAPY'.

- SH2D1B|117157 , SSR2|6746 , KDM5C|8242 , WBSCR22|114049 , ZNF512|84450 , ...

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=35 | older | N=17 | younger | N=18
GENDER | t test | N=35 | male | N=15 | female | N=20
HISTOLOGICAL TYPE | ANOVA test | N=3273 |  |  |  |
RADIATIONS RADIATION REGIMENINDICATION | t test | N=35 | yes | N=21 | no | N=14
NEOADJUVANT THERAPY | t test | N=137 | yes | N=49 | no | N=88

Clinical variable #1: 'AGE'

35 genes related to 'AGE'.

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

AGE | Mean (SD) | 47.29 (16)
| Significant markers | N = 35
| pos. correlated | 17
| neg. correlated | 18

List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

Table S2. Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
CD97|976 | -0.42 | 8.821e-09 | 0.000159
C12ORF52|84934 | 0.4072 | 2.695e-08 | 0.000484
KBTBD2|25948 | -0.3929 | 8.932e-08 | 0.00161
GPR173|54328 | -0.3903 | 1.201e-07 | 0.00216
GOT2|2806 | 0.3834 | 1.929e-07 | 0.00347
HADH|3033 | 0.3813 | 2.268e-07 | 0.00407
ANO10|55129 | 0.3738 | 4.064e-07 | 0.0073
ZNF518B|85460 | -0.3733 | 4.222e-07 | 0.00758
RBMXL1|494115 | -0.3707 | 5.15e-07 | 0.00925
ZCCHC12|170261 | -0.3693 | 5.748e-07 | 0.0103

Figure S1. Get High-res Image As an example, this figure shows the association of CD97|976 to 'AGE'. P value = 8.82e-09 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #2: 'GENDER'

35 genes related to 'GENDER'.

Table S3. Basic characteristics of clinical feature: 'GENDER'

GENDER | Labels | N
| FEMALE | 124
| MALE | 49
| Significant markers | N = 35
| Higher in MALE | 15
| Higher in FEMALE | 20

List of top 10 genes differentially expressed by 'GENDER'

Table S4. Get Full Table List of top 10 genes differentially expressed by 'GENDER'

| T(pos if higher in 'MALE') | ttestP | Q | AUC
--- | --- | --- | --- | ---
DDX3Y|8653 | 68.6 | 1.735e-91 | 3.12e-87 | 1
RPS4Y1|6192 | 56.21 | 8.425e-87 | 1.51e-82 | 1
ZFY|7544 | 58.49 | 7.266e-81 | 1.31e-76 | 1
USP9Y|8287 | 58.77 | 8.898e-73 | 1.6e-68 | 1
UTY|7404 | 59.57 | 1.72e-68 | 3.09e-64 | 1
KDM5D|8284 | 60.13 | 1.562e-63 | 2.81e-59 | 1
NLGN4Y|22829 | 42.15 | 3.579e-58 | 6.43e-54 | 1
PRKY|5616 | 26.12 | 6.148e-58 | 1.1e-53 | 0.9977
CYORF15A|246126 | 47.28 | 3.441e-49 | 6.18e-45 | 1
CYORF15B|84663 | 45.91 | 1.438e-47 | 2.58e-43 | 1

Figure S2. Get High-res Image As an example, this figure shows the association of DDX3Y|8653 to 'GENDER'. P value = 1.73e-91 with T-test analysis.

Clinical variable #3: 'HISTOLOGICAL.TYPE'

3273 genes related to 'HISTOLOGICAL.TYPE'.

Table S5. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE | Labels | N
| OTHER | 7
| THYROID PAPILLARY CARCINOMA - CLASSICAL/USUAL | 92
| THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED) | 54
| THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES) | 20
| Significant markers | N = 3273

List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S6. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

| ANOVA_P | Q
--- | --- | ---
ANKLE2|23141 | 1.911e-25 | 3.43e-21
FN1|2335 | 5.338e-25 | 9.59e-21
LDLR|3949 | 4.187e-24 | 7.52e-20
FAM176A|84141 | 8.629e-24 | 1.55e-19
TMPRSS6|164656 | 4.312e-23 | 7.75e-19
PTPRE|5791 | 1.649e-22 | 2.96e-18
ITGA3|3675 | 5.806e-22 | 1.04e-17
CREB5|9586 | 7.454e-22 | 1.34e-17
GABRB2|2561 | 1.389e-21 | 2.5e-17
SFTPB|6439 | 1.715e-21 | 3.08e-17

Figure S3. Get High-res Image As an example, this figure shows the association of ANKLE2|23141 to 'HISTOLOGICAL.TYPE'. P value = 1.91e-25 with ANOVA analysis.

Clinical variable #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S7. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N
| NO | 12
| YES | 161
| Significant markers | N = 35
| Higher in YES | 21
| Higher in NO | 14

List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S8. Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

| T(pos if higher in 'YES') | ttestP | Q | AUC
--- | --- | --- | --- | ---
FLJ37543|285668 | 10.35 | 2.498e-14 | 4.47e-10 | 0.8601
C14ORF180|400258 | 7.47 | 2.348e-10 | 4.21e-06 | 0.8444
A2ML1|144568 | 7.31 | 2.073e-09 | 3.71e-05 | 0.7921
DNAH14|127602 | -8.51 | 9.407e-09 | 0.000168 | 0.8799
LOC440173|440173 | 7.17 | 1.739e-08 | 0.000311 | 0.9012
HPR|3250 | 7.24 | 9.212e-08 | 0.00165 | 0.9138
HCFC1|3054 | -7.96 | 9.399e-08 | 0.00168 | 0.8665
TMEM20|159371 | 7.21 | 1.462e-07 | 0.00262 | 0.8245
ENPP3|5169 | 6.96 | 1.49e-07 | 0.00267 | 0.836
DOCK3|1795 | -6.56 | 1.936e-07 | 0.00347 | 0.8163

Figure S4. Get High-res Image As an example, this figure shows the association of FLJ37543|285668 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 2.5e-14 with T-test analysis.

Clinical variable #5: 'NEOADJUVANT.THERAPY'

137 genes related to 'NEOADJUVANT.THERAPY'.

Table S9. Basic characteristics of clinical feature: 'NEOADJUVANT.THERAPY'

NEOADJUVANT.THERAPY | Labels | N
| NO | 3
| YES | 170
| Significant markers | N = 137
| Higher in YES | 49
| Higher in NO | 88

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

Table S10. Get Full Table List of top 10 genes differentially expressed by 'NEOADJUVANT.THERAPY'

| T(pos if higher in 'YES') | ttestP | Q | AUC
--- | --- | --- | --- | ---
SH2D1B|117157 | 20.13 | 3.095e-39 | 5.11e-35 | 0.9444
SSR2|6746 | 16.35 | 1.05e-34 | 1.73e-30 | 0.9098
KDM5C|8242 | -17.39 | 2.235e-34 | 3.69e-30 | 0.9549
WBSCR22|114049 | 15.72 | 2.676e-34 | 4.42e-30 | 0.9039
ZNF512|84450 | -15.39 | 1.142e-32 | 1.89e-28 | 0.9392
L3MBTL|26013 | -18.47 | 3.667e-30 | 6.06e-26 | 0.9412
SGSM1|129049 | -13.92 | 6.37e-30 | 1.05e-25 | 0.9118
PPP1R12A|4659 | -13.41 | 1.031e-27 | 1.7e-23 | 0.9412
POLDIP3|84271 | -12.48 | 8.763e-26 | 1.45e-21 | 0.8647
FCRL5|83416 | 17.79 | 5.804e-25 | 9.58e-21 | 0.9514

Figure S5. Get High-res Image As an example, this figure shows the association of SH2D1B|117157 to 'NEOADJUVANT.THERAPY'. P value = 3.09e-39 with T-test analysis.

Methods & Data
Input

- Expresson data file = THCA.uncv2.mRNAseq_RSEM_normalized_log2.txt

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

- Number of patients = 173

- Number of genes = 17972

- Number of clinical features = 5

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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