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 17948 genes and 5 clinical features across 117 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

- 24 genes correlated to 'AGE'.

- KBTBD2|25948 , DUSP6|1848 , DDIT4L|115265 , CD97|976 , NDEL1|81565 , ...

- 26 genes correlated to 'GENDER'.

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

- 2373 genes correlated to 'HISTOLOGICAL.TYPE'.

- PDHA1|5160 , GOT2|2806 , ITGA3|3675 , KCNIP3|30818 , COQ9|57017 , ...

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

- FLJ37543|285668 , DNAH14|127602 , ORC1L|4998 , CUL7|9820 , C14ORF180|400258 , ...

- 160 genes correlated to 'NEOADJUVANT.THERAPY'.

- SH2D1B|117157 , L3MBTL|26013 , KDM5C|8242 , SSR2|6746 , 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=24 | older | N=6 | younger | N=18
GENDER | t test | N=26 | male | N=14 | female | N=12
HISTOLOGICAL TYPE | ANOVA test | N=2373 |  |  |  |
RADIATIONS RADIATION REGIMENINDICATION | t test | N=20 | yes | N=5 | no | N=15
NEOADJUVANT THERAPY | t test | N=160 | yes | N=52 | no | N=108

Clinical variable #1: 'AGE'

24 genes related to 'AGE'.

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

AGE | Mean (SD) | 47.87 (16)
| Significant markers | N = 24
| pos. correlated | 6
| 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
--- | --- | --- | ---
KBTBD2|25948 | -0.4718 | 7.914e-08 | 0.00142
DUSP6|1848 | -0.4689 | 9.692e-08 | 0.00174
DDIT4L|115265 | 0.4576 | 2.136e-07 | 0.00383
CD97|976 | -0.4537 | 2.785e-07 | 0.005
NDEL1|81565 | -0.4515 | 3.223e-07 | 0.00578
MST1P9|11223 | -0.45 | 3.572e-07 | 0.00641
ZCCHC12|170261 | -0.4474 | 4.249e-07 | 0.00762
TMEM49|81671 | -0.4444 | 5.188e-07 | 0.00931
LOC401431|401431 | 0.4387 | 7.538e-07 | 0.0135
TUBGCP5|114791 | 0.4305 | 1.269e-06 | 0.0228

Figure S1. Get High-res Image As an example, this figure shows the association of KBTBD2|25948 to 'AGE'. P value = 7.91e-08 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #2: 'GENDER'

26 genes related to 'GENDER'.

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

GENDER | Labels | N
| FEMALE | 82
| MALE | 35
| Significant markers | N = 26
| Higher in MALE | 14
| Higher in FEMALE | 12

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 | 59.71 | 6.161e-64 | 1.11e-59 | 1
RPS4Y1|6192 | 46.8 | 2.566e-62 | 4.6e-58 | 1
ZFY|7544 | 52.4 | 3.091e-60 | 5.55e-56 | 1
USP9Y|8287 | 53.54 | 2.669e-56 | 4.79e-52 | 1
UTY|7404 | 54.49 | 2.087e-49 | 3.74e-45 | 1
NLGN4Y|22829 | 39 | 1.549e-46 | 2.78e-42 | 1
KDM5D|8284 | 51.88 | 4.417e-41 | 7.92e-37 | 1
PRKY|5616 | 21.44 | 1.354e-40 | 2.43e-36 | 0.9981
CYORF15A|246126 | 42.66 | 4.364e-31 | 7.83e-27 | 1
TSIX|9383 | -17.49 | 8.176e-25 | 1.47e-20 | 0.9994

Figure S2. Get High-res Image As an example, this figure shows the association of DDX3Y|8653 to 'GENDER'. P value = 6.16e-64 with T-test analysis.

Clinical variable #3: 'HISTOLOGICAL.TYPE'

2373 genes related to 'HISTOLOGICAL.TYPE'.

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

HISTOLOGICAL.TYPE | Labels | N
| OTHER | 3
| THYROID PAPILLARY CARCINOMA - CLASSICAL/USUAL | 65
| THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED) | 33
| THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES) | 16
| Significant markers | N = 2373

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
--- | --- | ---
PDHA1|5160 | 2.634e-20 | 4.73e-16
GOT2|2806 | 1.895e-19 | 3.4e-15
ITGA3|3675 | 5.861e-19 | 1.05e-14
KCNIP3|30818 | 2.222e-18 | 3.99e-14
COQ9|57017 | 3.381e-18 | 6.07e-14
ERBB3|2065 | 5.06e-18 | 9.08e-14
MPZL2|10205 | 9.197e-18 | 1.65e-13
ALDH1B1|219 | 1.006e-17 | 1.81e-13
LDLR|3949 | 4.891e-17 | 8.77e-13
SFTPB|6439 | 4.901e-17 | 8.79e-13

Figure S3. Get High-res Image As an example, this figure shows the association of PDHA1|5160 to 'HISTOLOGICAL.TYPE'. P value = 2.63e-20 with ANOVA analysis.

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

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

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

RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N
| NO | 11
| YES | 106
| Significant markers | N = 20
| Higher in YES | 5
| Higher in NO | 15

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 | 8.88 | 2.01e-12 | 3.6e-08 | 0.8627
DNAH14|127602 | -8.49 | 9.44e-09 | 0.000169 | 0.9177
ORC1L|4998 | -6.59 | 7.223e-08 | 0.00129 | 0.8182
CUL7|9820 | -7.41 | 1.356e-07 | 0.00243 | 0.8868
C14ORF180|400258 | 6.14 | 1.798e-07 | 0.00322 | 0.8889
MCM10|55388 | -6.48 | 2.354e-07 | 0.00421 | 0.8062
ZNF695|57116 | -6.96 | 3.019e-07 | 0.0054 | 0.8533
HCFC1|3054 | -7.08 | 4.14e-07 | 0.00741 | 0.8619
GINS1|9837 | -5.66 | 4.536e-07 | 0.00811 | 0.7933
CDC45|8318 | -6.56 | 7.549e-07 | 0.0135 | 0.8459

Figure S4. Get High-res Image As an example, this figure shows the association of FLJ37543|285668 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 2.01e-12 with T-test analysis.

Clinical variable #5: 'NEOADJUVANT.THERAPY'

160 genes related to 'NEOADJUVANT.THERAPY'.

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

NEOADJUVANT.THERAPY | Labels | N
| NO | 3
| YES | 114
| Significant markers | N = 160
| Higher in YES | 52
| Higher in NO | 108

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 | 17.79 | 3.175e-32 | 5.25e-28 | 0.9497
L3MBTL|26013 | -16.4 | 2.469e-28 | 4.08e-24 | 0.9444
KDM5C|8242 | -14.35 | 1.554e-26 | 2.57e-22 | 0.9591
SSR2|6746 | 13.74 | 8.9e-26 | 1.47e-21 | 0.9269
ZNF512|84450 | -12.96 | 3.994e-24 | 6.6e-20 | 0.9357
FCRL5|83416 | 15.22 | 1.584e-23 | 2.62e-19 | 0.9485
ZNF418|147686 | -13.15 | 1.649e-20 | 2.72e-16 | 0.9561
WBSCR22|114049 | 11.29 | 2.385e-20 | 3.94e-16 | 0.8655
SGSM1|129049 | -11.16 | 5.105e-20 | 8.43e-16 | 0.8947
C1ORF104|284618 | -13.15 | 5.32e-20 | 8.79e-16 | 0.886

Figure S5. Get High-res Image As an example, this figure shows the association of SH2D1B|117157 to 'NEOADJUVANT.THERAPY'. P value = 3.17e-32 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 = 117

- Number of genes = 17948

- 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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