Lung 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 18330 genes and 11 clinical features across 286 samples, statistically thresholded by Q value < 0.05, 9 clinical features related to at least one genes.

- 7 genes correlated to 'Time to Death'.

- ESYT3|83850 , UCN2|90226 , MYLIP|29116 , DKK1|22943 , LYAR|55646 , ...

- 1 gene correlated to 'AGE'.

- C11ORF84|144097

- 33 genes correlated to 'GENDER'.

- PRKY|5616 , ZFY|7544 , XIST|7503 , RPS4Y1|6192 , DDX3Y|8653 , ...

- 12 genes correlated to 'HISTOLOGICAL.TYPE'.

- A4GNT|51146 , DPCR1|135656 , TIGD2|166815 , SOX10|6663 , REG4|83998 , ...

- 6 genes correlated to 'PATHOLOGY.T'.

- FAM125B|89853 , ZNF671|79891 , MS4A1|931 , MAL|4118 , NELL2|4753 , ...

- 3 genes correlated to 'PATHOLOGY.N'.

- RARS|5917 , ZNF483|158399 , FAM117A|81558

- 72 genes correlated to 'PATHOLOGICSPREAD(M)'.

- C19ORF10|56005 , MLL5|55904 , MPG|4350 , PPIG|9360 , MRPL41|64975 , ...

- 6 genes correlated to 'TUMOR.STAGE'.

- ZNF540|163255 , RNASE1|6035 , FAM117A|81558 , RARS|5917 , ST6GAL1|6480 , ...

- 1 gene correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

- LRTM2|654429

- No genes correlated to 'KARNOFSKY.PERFORMANCE.SCORE', 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=7 | shorter survival | N=5 | longer survival | N=2
AGE | Spearman correlation test | N=1 | older | N=0 | younger | N=1
GENDER | t test | N=33 | male | N=16 | female | N=17
KARNOFSKY PERFORMANCE SCORE | Spearman correlation test | N=0 |  |  |  |
HISTOLOGICAL TYPE | ANOVA test | N=12 |  |  |  |
PATHOLOGY T | Spearman correlation test | N=6 | higher pT | N=0 | lower pT | N=6
PATHOLOGY N | Spearman correlation test | N=3 | higher pN | N=1 | lower pN | N=2
PATHOLOGICSPREAD(M) | ANOVA test | N=72 |  |  |  |
TUMOR STAGE | Spearman correlation test | N=6 | higher stage | N=1 | lower stage | N=5
RADIATIONS RADIATION REGIMENINDICATION | t test | N=1 | yes | N=1 | no | N=0
NEOADJUVANT THERAPY | t test | N=0 |  |  |  |

Clinical variable #1: 'Time to Death'

7 genes related to 'Time to Death'.

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

Time to Death | Duration (Months) | 0-224 (median=13.4)
| censored | N = 173
| death | N = 79
| Significant markers | N = 7
| associated with shorter survival | 5
| associated with longer survival | 2

List of 7 genes significantly associated with 'Time to Death' by Cox regression test

Table S2. Get Full Table List of 7 genes significantly associated with 'Time to Death' by Cox regression test

| HazardRatio | Wald_P | Q | C_index
--- | --- | --- | --- | ---
ESYT3|83850 | 0.73 | 1.406e-07 | 0.0026 | 0.352
UCN2|90226 | 1.36 | 2.561e-07 | 0.0047 | 0.65
MYLIP|29116 | 0.51 | 1.057e-06 | 0.019 | 0.345
DKK1|22943 | 1.2 | 1.339e-06 | 0.025 | 0.714
LYAR|55646 | 2.3 | 1.431e-06 | 0.026 | 0.652
MFSD2B|388931 | 1.69 | 1.657e-06 | 0.03 | 0.672
PPP1R3G|648791 | 1.53 | 1.88e-06 | 0.034 | 0.668

Figure S1. Get High-res Image As an example, this figure shows the association of ESYT3|83850 to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 1.41e-07 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) | 65.58 (9.6)
| Significant markers | N = 1
| pos. correlated | 0
| neg. correlated | 1

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
--- | --- | --- | ---
C11ORF84|144097 | -0.29 | 2.483e-06 | 0.0455

Figure S2. Get High-res Image As an example, this figure shows the association of C11ORF84|144097 to 'AGE'. P value = 2.48e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'GENDER'

33 genes related to 'GENDER'.

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

GENDER | Labels | N
| FEMALE | 155
| MALE | 131
| Significant markers | N = 33
| Higher in MALE | 16
| Higher in FEMALE | 17

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
--- | --- | --- | --- | ---
PRKY|5616 | 40.47 | 2.068e-113 | 3.79e-109 | 0.9992
ZFY|7544 | 45.78 | 4.218e-83 | 7.73e-79 | 0.9975
XIST|7503 | -33.67 | 4.407e-72 | 8.08e-68 | 0.986
RPS4Y1|6192 | 42.2 | 1.924e-70 | 3.53e-66 | 0.9958
DDX3Y|8653 | 38.51 | 8.154e-48 | 1.49e-43 | 0.9967
NLGN4Y|22829 | 22.93 | 7.495e-37 | 1.37e-32 | 0.9903
TSIX|9383 | -17.4 | 9.56e-31 | 1.75e-26 | 0.9861
KDM5D|8284 | 29.51 | 4.108e-29 | 7.53e-25 | 0.9971
USP9Y|8287 | 29.81 | 4.32e-29 | 7.91e-25 | 0.9995
ZRSR2|8233 | -9.62 | 4.897e-19 | 8.97e-15 | 0.8063

Figure S3. Get High-res Image As an example, this figure shows the association of PRKY|5616 to 'GENDER'. P value = 2.07e-113 with T-test analysis.

Clinical variable #4: 'KARNOFSKY.PERFORMANCE.SCORE'

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

Table S7. Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE | Mean (SD) | 74.23 (34)
| Significant markers | N = 0

Clinical variable #5: 'HISTOLOGICAL.TYPE'

12 genes related to 'HISTOLOGICAL.TYPE'.

Table S8. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE | Labels | N
| LUNG ACINAR ADENOCARCINOMA | 6
| LUNG ADENOCARCINOMA MIXED SUBTYPE | 64
| LUNG ADENOCARCINOMA- NOT OTHERWISE SPECIFIED (NOS) | 181
| LUNG BRONCHIOLOALVEOLAR CARCINOMA MUCINOUS | 3
| LUNG BRONCHIOLOALVEOLAR CARCINOMA NONMUCINOUS | 10
| LUNG CLEAR CELL ADENOCARCINOMA | 2
| LUNG MICROPAPILLARY ADENOCARCINOMA | 3
| LUNG MUCINOUS ADENOCARCINOMA | 2
| LUNG PAPILLARY ADENOCARCINOMA | 10
| LUNG SOLID PATTERN PREDOMINANT ADENOCARCINOMA | 1
| MUCINOUS (COLLOID) ADENOCARCINOMA | 4
| Significant markers | N = 12

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

Table S9. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

| ANOVA_P | Q
--- | --- | ---
A4GNT|51146 | 5.108e-09 | 9.36e-05
DPCR1|135656 | 9.904e-09 | 0.000182
TIGD2|166815 | 4.139e-08 | 0.000759
SOX10|6663 | 1.783e-07 | 0.00327
REG4|83998 | 1.799e-07 | 0.0033
MYO1A|4640 | 2.354e-07 | 0.00431
ELOVL5|60481 | 3.394e-07 | 0.00622
MIA|8190 | 4.038e-07 | 0.0074
FER1L6|654463 | 7.951e-07 | 0.0146
CA2|760 | 8.252e-07 | 0.0151

Figure S4. Get High-res Image As an example, this figure shows the association of A4GNT|51146 to 'HISTOLOGICAL.TYPE'. P value = 5.11e-09 with ANOVA analysis.

Clinical variable #6: 'PATHOLOGY.T'

6 genes related to 'PATHOLOGY.T'.

Table S10. Basic characteristics of clinical feature: 'PATHOLOGY.T'

PATHOLOGY.T | Mean (SD) | 1.92 (0.76)
|  | N
| T1 | 79
| T2 | 167
| T3 | 23
| T4 | 16
| Significant markers | N = 6
| pos. correlated | 0
| neg. correlated | 6

List of 6 genes significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

Table S11. Get Full Table List of 6 genes significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
FAM125B|89853 | -0.3179 | 4.112e-08 | 0.000754
ZNF671|79891 | -0.2922 | 5.155e-07 | 0.00945
MS4A1|931 | -0.2845 | 1.095e-06 | 0.0201
MAL|4118 | -0.2837 | 1.124e-06 | 0.0206
NELL2|4753 | -0.2807 | 1.47e-06 | 0.0269
ZNF879|345462 | -0.2758 | 2.265e-06 | 0.0415

Figure S5. Get High-res Image As an example, this figure shows the association of FAM125B|89853 to 'PATHOLOGY.T'. P value = 4.11e-08 with Spearman correlation analysis.

Clinical variable #7: 'PATHOLOGY.N'

3 genes related to 'PATHOLOGY.N'.

Table S12. Basic characteristics of clinical feature: 'PATHOLOGY.N'

PATHOLOGY.N | Mean (SD) | 0.57 (0.79)
|  | N
| N0 | 171
| N1 | 58
| N2 | 50
| N3 | 1
| Significant markers | N = 3
| pos. correlated | 1
| neg. correlated | 2

List of 3 genes significantly correlated to 'PATHOLOGY.N' by Spearman correlation test

Table S13. Get Full Table List of 3 genes significantly correlated to 'PATHOLOGY.N' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
RARS|5917 | 0.3141 | 7.884e-08 | 0.00145
ZNF483|158399 | -0.2934 | 5.79e-07 | 0.0106
FAM117A|81558 | -0.278 | 2.303e-06 | 0.0422

Figure S6. Get High-res Image As an example, this figure shows the association of RARS|5917 to 'PATHOLOGY.N'. P value = 7.88e-08 with Spearman correlation analysis.

Clinical variable #8: 'PATHOLOGICSPREAD(M)'

72 genes related to 'PATHOLOGICSPREAD(M)'.

Table S14. Basic characteristics of clinical feature: 'PATHOLOGICSPREAD(M)'

PATHOLOGICSPREAD(M) | Labels | N
| M0 | 199
| M1 | 16
| MX | 64
| Significant markers | N = 72

List of top 10 genes differentially expressed by 'PATHOLOGICSPREAD(M)'

Table S15. Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGICSPREAD(M)'

| ANOVA_P | Q
--- | --- | ---
C19ORF10|56005 | 7.924e-09 | 0.000145
MLL5|55904 | 8.957e-09 | 0.000164
MPG|4350 | 4.589e-08 | 0.000841
PPIG|9360 | 8.781e-08 | 0.00161
MRPL41|64975 | 1.155e-07 | 0.00212
UQCRQ|27089 | 1.167e-07 | 0.00214
ZNF37B|100129482 | 1.284e-07 | 0.00235
PCF11|51585 | 1.431e-07 | 0.00262
NCRNA00116|205251 | 1.442e-07 | 0.00264
CHCHD5|84269 | 1.479e-07 | 0.00271

Figure S7. Get High-res Image As an example, this figure shows the association of C19ORF10|56005 to 'PATHOLOGICSPREAD(M)'. P value = 7.92e-09 with ANOVA analysis.

Clinical variable #9: 'TUMOR.STAGE'

6 genes related to 'TUMOR.STAGE'.

Table S16. Basic characteristics of clinical feature: 'TUMOR.STAGE'

TUMOR.STAGE | Mean (SD) | 1.79 (0.96)
|  | N
| Stage 1 | 147
| Stage 2 | 61
| Stage 3 | 57
| Stage 4 | 16
| Significant markers | N = 6
| pos. correlated | 1
| neg. correlated | 5

List of 6 genes significantly correlated to 'TUMOR.STAGE' by Spearman correlation test

Table S17. Get Full Table List of 6 genes significantly correlated to 'TUMOR.STAGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
ZNF540|163255 | -0.2917 | 6.449e-07 | 0.0118
RNASE1|6035 | -0.2897 | 7.747e-07 | 0.0142
FAM117A|81558 | -0.2865 | 1.039e-06 | 0.019
RARS|5917 | 0.284 | 1.305e-06 | 0.0239
ST6GAL1|6480 | -0.2809 | 1.708e-06 | 0.0313
ZFP3|124961 | -0.2777 | 2.262e-06 | 0.0414

Figure S8. Get High-res Image As an example, this figure shows the association of ZNF540|163255 to 'TUMOR.STAGE'. P value = 6.45e-07 with Spearman correlation analysis.

Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

One gene related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S18. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N
| NO | 17
| YES | 269
| Significant markers | N = 1
| Higher in YES | 1
| Higher in NO | 0

List of one gene differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S19. Get Full Table List of one gene differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

| T(pos if higher in 'YES') | ttestP | Q | AUC
--- | --- | --- | --- | ---
LRTM2|654429 | 4.99 | 2.567e-06 | 0.047 | 0.744

Figure S9. Get High-res Image As an example, this figure shows the association of LRTM2|654429 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 2.57e-06 with T-test analysis.

Clinical variable #11: 'NEOADJUVANT.THERAPY'

No gene related to 'NEOADJUVANT.THERAPY'.

Table S20. Basic characteristics of clinical feature: 'NEOADJUVANT.THERAPY'

NEOADJUVANT.THERAPY | Labels | N
| NO | 44
| YES | 242
| Significant markers | N = 0

Methods & Data
Input

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

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

- Number of patients = 286

- Number of genes = 18330

- Number of clinical features = 11

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

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] 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] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[5] 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)
Copyright © 2012 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle