Head and Neck Squamous Cell Carcinoma: 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 18384 genes and 8 clinical features across 286 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

- 10 genes correlated to 'Time to Death'.

- FGD3|89846 , CYB5B|80777 , TOMM34|10953 , SLC25A45|283130 , SEC11A|23478 , ...

- 1 gene correlated to 'AGE'.

- RNASE3|6037

- 31 genes correlated to 'GENDER'.

- XIST|7503 , ZFY|7544 , PRKY|5616 , RPS4Y1|6192 , TSIX|9383 , ...

- 2 genes correlated to 'PATHOLOGY.T'.

- LRRC8A|56262 , GTF3C4|9329

- 9 genes correlated to 'PATHOLOGY.N'.

- SPRR2F|6705 , TGM1|7051 , CRCT1|54544 , SPOCK1|6695 , PTDSS1|9791 , ...

- No genes correlated to 'TUMOR.STAGE', 'RADIATIONS.RADIATION.REGIMENINDICATION', and 'NEOADJUVANT.THERAPY'.

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 |
--- | --- | --- | --- | --- | --- | ---
Time to Death | Cox regression test | N=10 | shorter survival | N=4 | longer survival | N=6
AGE | Spearman correlation test | N=1 | older | N=1 | younger | N=0
GENDER | t test | N=31 | male | N=13 | female | N=18
PATHOLOGY T | Spearman correlation test | N=2 | higher pT | N=2 | lower pT | N=0
PATHOLOGY N | Spearman correlation test | N=9 | higher pN | N=4 | lower pN | N=5
TUMOR STAGE | Spearman correlation test | N=0 |  |  |  |
RADIATIONS RADIATION REGIMENINDICATION | t test | N=0 |  |  |  |
NEOADJUVANT THERAPY | t test | N=0 |  |  |  |

Clinical variable #1: 'Time to Death'

10 genes related to 'Time to Death'.

Table S1. Basic characteristics of clinical feature: 'Time to Death'

Time to Death | Duration (Months) | 0.1-210.9 (median=14.8)
| censored | N = 164
| death | N = 119
| Significant markers | N = 10
| associated with shorter survival | 4
| associated with longer survival | 6

List of 10 genes significantly associated with 'Time to Death' by Cox regression test

Table S2. Get Full Table List of 10 genes significantly associated with 'Time to Death' by Cox regression test

| HazardRatio | Wald_P | Q | C_index
--- | --- | --- | --- | ---
FGD3|89846 | 0.61 | 4.315e-09 | 7.9e-05 | 0.327
CYB5B|80777 | 2.4 | 1.271e-07 | 0.0023 | 0.627
TOMM34|10953 | 2.3 | 3.724e-07 | 0.0068 | 0.642
SLC25A45|283130 | 0.58 | 6.282e-07 | 0.012 | 0.355
SEC11A|23478 | 2.8 | 8.815e-07 | 0.016 | 0.642
LOC728989|728989 | 0.65 | 1.035e-06 | 0.019 | 0.337
TXNDC9|10190 | 2.2 | 1.08e-06 | 0.02 | 0.597
TP53INP1|94241 | 0.64 | 1.171e-06 | 0.022 | 0.359
DUSP16|80824 | 0.46 | 2.09e-06 | 0.038 | 0.38
SLC35E2|728661 | 0.57 | 2.601e-06 | 0.048 | 0.384

Figure S1. Get High-res Image As an example, this figure shows the association of FGD3|89846 to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 4.31e-09 with univariate Cox regression analysis using continuous log-2 expression values.

Clinical variable #2: 'AGE'

One gene related to 'AGE'.

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

AGE | Mean (SD) | 61.29 (12)
| Significant markers | N = 1
| pos. correlated | 1
| neg. correlated | 0

List of one gene significantly correlated to 'AGE' by Spearman correlation test

Table S4. Get Full Table List of one gene significantly correlated to 'AGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
RNASE3|6037 | 0.3443 | 1.499e-06 | 0.0276

Figure S2. Get High-res Image As an example, this figure shows the association of RNASE3|6037 to 'AGE'. P value = 1.5e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'GENDER'

31 genes related to 'GENDER'.

Table S5. Basic characteristics of clinical feature: 'GENDER'

GENDER | Labels | N
| FEMALE | 78
| MALE | 208
| Significant markers | N = 31
| Higher in MALE | 13
| Higher in FEMALE | 18

List of top 10 genes differentially expressed by 'GENDER'

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

| T(pos if higher in 'MALE') | ttestP | Q | AUC
--- | --- | --- | --- | ---
XIST|7503 | -36.19 | 4.122e-85 | 7.58e-81 | 0.9897
ZFY|7544 | 31.27 | 1.245e-56 | 2.29e-52 | 0.9852
PRKY|5616 | 23.72 | 3.719e-49 | 6.84e-45 | 0.9823
RPS4Y1|6192 | 29.28 | 4.89e-46 | 8.99e-42 | 0.9872
TSIX|9383 | -15.96 | 2.675e-33 | 4.92e-29 | 0.9594
DDX3Y|8653 | 25.54 | 3.428e-33 | 6.3e-29 | 0.9784
USP9Y|8287 | 20.55 | 1.996e-24 | 3.67e-20 | 0.9783
KDM5D|8284 | 20.14 | 6.591e-23 | 1.21e-18 | 0.976
NLGN4Y|22829 | 17.37 | 1.06e-21 | 1.95e-17 | 0.9687
UTY|7404 | 18.04 | 4.107e-20 | 7.55e-16 | 0.971

Figure S3. Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 4.12e-85 with T-test analysis.

Clinical variable #4: 'PATHOLOGY.T'

2 genes related to 'PATHOLOGY.T'.

Table S7. Basic characteristics of clinical feature: 'PATHOLOGY.T'

PATHOLOGY.T | Mean (SD) | 2.93 (1)
|  | N
| T1 | 20
| T2 | 76
| T3 | 58
| T4 | 98
| Significant markers | N = 2
| pos. correlated | 2
| neg. correlated | 0

List of 2 genes significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

Table S8. Get Full Table List of 2 genes significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
LRRC8A|56262 | 0.3379 | 3.808e-08 | 7e-04
GTF3C4|9329 | 0.2948 | 1.903e-06 | 0.035

Figure S4. Get High-res Image As an example, this figure shows the association of LRRC8A|56262 to 'PATHOLOGY.T'. P value = 3.81e-08 with Spearman correlation analysis.

Clinical variable #5: 'PATHOLOGY.N'

9 genes related to 'PATHOLOGY.N'.

Table S9. Basic characteristics of clinical feature: 'PATHOLOGY.N'

PATHOLOGY.N | Mean (SD) | 1.03 (0.96)
|  | N
| N0 | 95
| N1 | 31
| N2 | 94
| N3 | 4
| Significant markers | N = 9
| pos. correlated | 4
| neg. correlated | 5

List of 9 genes significantly correlated to 'PATHOLOGY.N' by Spearman correlation test

Table S10. Get Full Table List of 9 genes significantly correlated to 'PATHOLOGY.N' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
SPRR2F|6705 | -0.3577 | 4.863e-08 | 0.000894
TGM1|7051 | -0.3441 | 1.27e-07 | 0.00233
CRCT1|54544 | -0.3413 | 2.093e-07 | 0.00385
SPOCK1|6695 | 0.3322 | 3.581e-07 | 0.00658
PTDSS1|9791 | 0.3297 | 4.459e-07 | 0.0082
GDPD3|79153 | -0.3179 | 1.19e-06 | 0.0219
TRMT12|55039 | 0.3157 | 1.416e-06 | 0.026
PPFIA1|8500 | 0.3118 | 1.933e-06 | 0.0355
MPZL2|10205 | -0.3109 | 2.078e-06 | 0.0382

Figure S5. Get High-res Image As an example, this figure shows the association of SPRR2F|6705 to 'PATHOLOGY.N'. P value = 4.86e-08 with Spearman correlation analysis.

Clinical variable #6: 'TUMOR.STAGE'

No gene related to 'TUMOR.STAGE'.

Table S11. Basic characteristics of clinical feature: 'TUMOR.STAGE'

TUMOR.STAGE | Mean (SD) | 3.3 (0.96)
|  | N
| Stage 1 | 14
| Stage 2 | 46
| Stage 3 | 39
| Stage 4 | 148
| Significant markers | N = 0

Clinical variable #7: 'RADIATIONS.RADIATION.REGIMENINDICATION'

No gene related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S12. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N
| NO | 75
| YES | 211
| Significant markers | N = 0

Clinical variable #8: 'NEOADJUVANT.THERAPY'

No gene related to 'NEOADJUVANT.THERAPY'.

Table S13. Basic characteristics of clinical feature: 'NEOADJUVANT.THERAPY'

NEOADJUVANT.THERAPY | Labels | N
| NO | 46
| YES | 240
| Significant markers | N = 0

Methods & Data
Input

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

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

- Number of patients = 286

- Number of genes = 18384

- Number of clinical features = 8

Survival analysis

For survival clinical features, Wald's test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values using the 'coxph' function in R. Kaplan-Meier survival curves were plot using the four quartile subgroups of patients based on expression levels

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] Andersen and Gill, Cox's regression model for counting processes, a large sample study, Annals of Statistics 10(4):1100-1120 (1982)
[2] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)
[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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