This pipeline uses various statistical tests to identify mRNAs whose expression levels correlated to selected clinical features.
Testing the association between 18310 genes and 14 clinical features across 354 samples, statistically thresholded by Q value < 0.05, 11 clinical features related to at least one genes.
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10 genes correlated to 'Time to Death'.
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ESYT3|83850 , UCN2|90226 , MYLIP|29116 , DKK1|22943 , LDLRAD3|143458 , ...
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3 genes correlated to 'AGE'.
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HSD17B2|3294 , GPR15|2838 , AHRR|57491
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85 genes correlated to 'GENDER'.
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PRKY|5616 , ZFY|7544 , RPS4Y1|6192 , XIST|7503 , DDX3Y|8653 , ...
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31 genes correlated to 'HISTOLOGICAL.TYPE'.
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CREB3L3|84699 , A4GNT|51146 , MIA|8190 , REG4|83998 , CRH|1392 , ...
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6 genes correlated to 'PATHOLOGY.T'.
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FAM125B|89853 , ZNF671|79891 , MS4A1|931 , MAL|4118 , NELL2|4753 , ...
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3 genes correlated to 'PATHOLOGY.N'.
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RARS|5917 , ZNF483|158399 , FAM117A|81558
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79 genes correlated to 'PATHOLOGICSPREAD(M)'.
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C19ORF10|56005 , MLL5|55904 , MPG|4350 , PPIG|9360 , MRPL41|64975 , ...
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6 genes correlated to 'TUMOR.STAGE'.
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ZNF540|163255 , RNASE1|6035 , FAM117A|81558 , RARS|5917 , ST6GAL1|6480 , ...
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2 genes correlated to 'NUMBERPACKYEARSSMOKED'.
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LOC723809|723809 , LHFPL3|375612
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134 genes correlated to 'TOBACCOSMOKINGHISTORYINDICATOR'.
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GPR15|2838 , DBF4B|80174 , C20ORF103|24141 , CASR|846 , KNTC1|9735 , ...
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2 genes correlated to 'YEAROFTOBACCOSMOKINGONSET'.
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ENTPD3|956 , GPR15|2838
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No genes correlated to 'KARNOFSKY.PERFORMANCE.SCORE', 'RADIATIONS.RADIATION.REGIMENINDICATION', and 'COMPLETENESS.OF.RESECTION'.
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=6 | longer survival | N=4 |
AGE | Spearman correlation test | N=3 | older | N=1 | younger | N=2 |
GENDER | t test | N=85 | male | N=29 | female | N=56 |
KARNOFSKY PERFORMANCE SCORE | Spearman correlation test | N=0 | ||||
HISTOLOGICAL TYPE | ANOVA test | N=31 | ||||
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=79 | ||||
TUMOR STAGE | Spearman correlation test | N=6 | higher stage | N=1 | lower stage | N=5 |
RADIATIONS RADIATION REGIMENINDICATION | t test | N=0 | ||||
NUMBERPACKYEARSSMOKED | Spearman correlation test | N=2 | higher numberpackyearssmoked | N=0 | lower numberpackyearssmoked | N=2 |
TOBACCOSMOKINGHISTORYINDICATOR | ANOVA test | N=134 | ||||
YEAROFTOBACCOSMOKINGONSET | Spearman correlation test | N=2 | higher yearoftobaccosmokingonset | N=1 | lower yearoftobaccosmokingonset | N=1 |
COMPLETENESS OF RESECTION | ANOVA test | N=0 |
Table S1. Basic characteristics of clinical feature: 'Time to Death'
Time to Death | Duration (Months) | 0-224 (median=8.5) |
censored | N = 234 | |
death | N = 81 | |
Significant markers | N = 10 | |
associated with shorter survival | 6 | |
associated with longer survival | 4 |
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 | |
---|---|---|---|---|
ESYT3|83850 | 0.73 | 2.225e-07 | 0.0041 | 0.368 |
UCN2|90226 | 1.36 | 4.319e-07 | 0.0079 | 0.635 |
MYLIP|29116 | 0.5 | 7.861e-07 | 0.014 | 0.35 |
DKK1|22943 | 1.2 | 9.717e-07 | 0.018 | 0.71 |
LDLRAD3|143458 | 1.55 | 1.686e-06 | 0.031 | 0.664 |
B3GNT8|374907 | 0.71 | 1.784e-06 | 0.033 | 0.339 |
LYAR|55646 | 2.3 | 1.823e-06 | 0.033 | 0.64 |
RGS20|8601 | 1.24 | 2.011e-06 | 0.037 | 0.663 |
PPP1R3G|648791 | 1.51 | 2.129e-06 | 0.039 | 0.655 |
FAM189A2|9413 | 0.77 | 2.177e-06 | 0.04 | 0.359 |
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 = 2.22e-07 with univariate Cox regression analysis using continuous log-2 expression values.
![](V1ex.png)
Table S3. Basic characteristics of clinical feature: 'AGE'
AGE | Mean (SD) | 65.2 (9.8) |
Significant markers | N = 3 | |
pos. correlated | 1 | |
neg. correlated | 2 |
Table S4. Get Full Table List of 3 genes significantly correlated to 'AGE' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
HSD17B2|3294 | 0.2704 | 1.068e-06 | 0.0196 |
GPR15|2838 | -0.2676 | 2.494e-06 | 0.0457 |
AHRR|57491 | -0.2582 | 2.67e-06 | 0.0489 |
Figure S2. Get High-res Image As an example, this figure shows the association of HSD17B2|3294 to 'AGE'. P value = 1.07e-06 with Spearman correlation analysis. The straight line presents the best linear regression.
![](V2ex.png)
Table S5. Basic characteristics of clinical feature: 'GENDER'
GENDER | Labels | N |
FEMALE | 191 | |
MALE | 163 | |
Significant markers | N = 85 | |
Higher in MALE | 29 | |
Higher in FEMALE | 56 |
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 | 45.81 | 3.572e-142 | 6.54e-138 | 0.9994 |
ZFY|7544 | 53.94 | 1.054e-117 | 1.93e-113 | 0.998 |
RPS4Y1|6192 | 49.02 | 1.536e-97 | 2.81e-93 | 0.9967 |
XIST|7503 | -36.21 | 1.936e-86 | 3.54e-82 | 0.9809 |
DDX3Y|8653 | 46.36 | 2.005e-66 | 3.67e-62 | 0.9976 |
KDM5D|8284 | 39.96 | 2.039e-51 | 3.73e-47 | 0.9984 |
NLGN4Y|22829 | 27.19 | 2.454e-50 | 4.49e-46 | 0.9914 |
USP9Y|8287 | 39.66 | 1.149e-48 | 2.1e-44 | 0.9996 |
TSIX|9383 | -18.52 | 4.287e-36 | 7.84e-32 | 0.9721 |
UTY|7404 | 27.19 | 4.833e-26 | 8.84e-22 | 0.9959 |
Figure S3. Get High-res Image As an example, this figure shows the association of PRKY|5616 to 'GENDER'. P value = 3.57e-142 with T-test analysis.
![](V3ex.png)
No gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.
Table S7. Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'
KARNOFSKY.PERFORMANCE.SCORE | Mean (SD) | 75.86 (32) |
Significant markers | N = 0 |
Table S8. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'
HISTOLOGICAL.TYPE | Labels | N |
LUNG ACINAR ADENOCARCINOMA | 10 | |
LUNG ADENOCARCINOMA MIXED SUBTYPE | 75 | |
LUNG ADENOCARCINOMA- NOT OTHERWISE SPECIFIED (NOS) | 214 | |
LUNG BRONCHIOLOALVEOLAR CARCINOMA MUCINOUS | 4 | |
LUNG BRONCHIOLOALVEOLAR CARCINOMA NONMUCINOUS | 17 | |
LUNG CLEAR CELL ADENOCARCINOMA | 2 | |
LUNG MICROPAPILLARY ADENOCARCINOMA | 3 | |
LUNG MUCINOUS ADENOCARCINOMA | 2 | |
LUNG PAPILLARY ADENOCARCINOMA | 17 | |
LUNG SOLID PATTERN PREDOMINANT ADENOCARCINOMA | 3 | |
MUCINOUS (COLLOID) ADENOCARCINOMA | 4 | |
MUCINOUS (COLLOID) CARCINOMA | 3 | |
Significant markers | N = 31 |
Table S9. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'
ANOVA_P | Q | |
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CREB3L3|84699 | 1.962e-11 | 3.59e-07 |
A4GNT|51146 | 4.565e-11 | 8.36e-07 |
MIA|8190 | 2.292e-10 | 4.2e-06 |
REG4|83998 | 3.74e-10 | 6.85e-06 |
CRH|1392 | 4.05e-09 | 7.41e-05 |
DPCR1|135656 | 4.085e-09 | 7.48e-05 |
ELOVL5|60481 | 1.325e-08 | 0.000243 |
FER1L6|654463 | 1.351e-08 | 0.000247 |
DNAH14|127602 | 2.418e-08 | 0.000443 |
SLC22A10|387775 | 5.538e-08 | 0.00101 |
Figure S4. Get High-res Image As an example, this figure shows the association of CREB3L3|84699 to 'HISTOLOGICAL.TYPE'. P value = 1.96e-11 with ANOVA analysis.
![](V5ex.png)
Table S10. Basic characteristics of clinical feature: 'PATHOLOGY.T'
PATHOLOGY.T | Mean (SD) | 1.92 (0.76) |
N | ||
T1 | 79 | |
T2 | 168 | |
T3 | 23 | |
T4 | 16 | |
Significant markers | N = 6 | |
pos. correlated | 0 | |
neg. correlated | 6 |
Table S11. Get Full Table List of 6 genes significantly correlated to 'PATHOLOGY.T' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
FAM125B|89853 | -0.318 | 3.865e-08 | 0.000708 |
ZNF671|79891 | -0.2903 | 5.846e-07 | 0.0107 |
MS4A1|931 | -0.2818 | 1.337e-06 | 0.0245 |
MAL|4118 | -0.2808 | 1.4e-06 | 0.0256 |
NELL2|4753 | -0.2798 | 1.528e-06 | 0.028 |
ZNF879|345462 | -0.2758 | 2.189e-06 | 0.0401 |
Figure S5. Get High-res Image As an example, this figure shows the association of FAM125B|89853 to 'PATHOLOGY.T'. P value = 3.87e-08 with Spearman correlation analysis.
![](V6ex.png)
Table S12. Basic characteristics of clinical feature: 'PATHOLOGY.N'
PATHOLOGY.N | Mean (SD) | 0.58 (0.79) |
N | ||
N0 | 171 | |
N1 | 59 | |
N2 | 50 | |
N3 | 1 | |
Significant markers | N = 3 | |
pos. correlated | 1 | |
neg. correlated | 2 |
Table S13. Get Full Table List of 3 genes significantly correlated to 'PATHOLOGY.N' by Spearman correlation test
SpearmanCorr | corrP | Q | |
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RARS|5917 | 0.3131 | 8.293e-08 | 0.00152 |
ZNF483|158399 | -0.293 | 5.761e-07 | 0.0105 |
FAM117A|81558 | -0.2758 | 2.687e-06 | 0.0492 |
Figure S6. Get High-res Image As an example, this figure shows the association of RARS|5917 to 'PATHOLOGY.N'. P value = 8.29e-08 with Spearman correlation analysis.
![](V7ex.png)
Table S14. Basic characteristics of clinical feature: 'PATHOLOGICSPREAD(M)'
PATHOLOGICSPREAD(M) | Labels | N |
M0 | 200 | |
M1 | 16 | |
MX | 64 | |
Significant markers | N = 79 |
Table S15. Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGICSPREAD(M)'
ANOVA_P | Q | |
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C19ORF10|56005 | 6.11e-09 | 0.000112 |
MLL5|55904 | 7.08e-09 | 0.00013 |
MPG|4350 | 3.621e-08 | 0.000663 |
PPIG|9360 | 7.197e-08 | 0.00132 |
MRPL41|64975 | 9.141e-08 | 0.00167 |
UQCRQ|27089 | 9.789e-08 | 0.00179 |
ZNF37B|100129482 | 1.051e-07 | 0.00192 |
PCF11|51585 | 1.169e-07 | 0.00214 |
NCRNA00116|205251 | 1.188e-07 | 0.00217 |
CHCHD5|84269 | 1.198e-07 | 0.00219 |
Figure S7. Get High-res Image As an example, this figure shows the association of C19ORF10|56005 to 'PATHOLOGICSPREAD(M)'. P value = 6.11e-09 with ANOVA analysis.
![](V8ex.png)
Table S16. Basic characteristics of clinical feature: 'TUMOR.STAGE'
TUMOR.STAGE | Mean (SD) | 1.79 (0.96) |
N | ||
Stage 1 | 148 | |
Stage 2 | 61 | |
Stage 3 | 57 | |
Stage 4 | 16 | |
Significant markers | N = 6 | |
pos. correlated | 1 | |
neg. correlated | 5 |
Table S17. Get Full Table List of 6 genes significantly correlated to 'TUMOR.STAGE' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
ZNF540|163255 | -0.2929 | 5.554e-07 | 0.0102 |
RNASE1|6035 | -0.2915 | 6.315e-07 | 0.0116 |
FAM117A|81558 | -0.2878 | 8.866e-07 | 0.0162 |
RARS|5917 | 0.284 | 1.244e-06 | 0.0228 |
ST6GAL1|6480 | -0.2798 | 1.819e-06 | 0.0333 |
ZFP3|124961 | -0.2751 | 2.728e-06 | 0.0499 |
Figure S8. Get High-res Image As an example, this figure shows the association of ZNF540|163255 to 'TUMOR.STAGE'. P value = 5.55e-07 with Spearman correlation analysis.
![](V9ex.png)
No gene related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
Table S18. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'
RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N |
NO | 19 | |
YES | 335 | |
Significant markers | N = 0 |
Table S19. Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'
NUMBERPACKYEARSSMOKED | Mean (SD) | 40.66 (27) |
Significant markers | N = 2 | |
pos. correlated | 0 | |
neg. correlated | 2 |
Table S20. Get Full Table List of 2 genes significantly correlated to 'NUMBERPACKYEARSSMOKED' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
LOC723809|723809 | -0.3142 | 1.601e-06 | 0.0293 |
LHFPL3|375612 | -0.3141 | 2.362e-06 | 0.0432 |
Figure S9. Get High-res Image As an example, this figure shows the association of LOC723809|723809 to 'NUMBERPACKYEARSSMOKED'. P value = 1.6e-06 with Spearman correlation analysis. The straight line presents the best linear regression.
![](V11ex.png)
134 genes related to 'TOBACCOSMOKINGHISTORYINDICATOR'.
Table S21. Basic characteristics of clinical feature: 'TOBACCOSMOKINGHISTORYINDICATOR'
TOBACCOSMOKINGHISTORYINDICATOR | Labels | N |
CURRENT REFORMED SMOKER FOR < OR = 15 YEARS | 100 | |
CURRENT REFORMED SMOKER FOR > 15 YEARS | 78 | |
CURRENT SMOKER | 61 | |
LIFELONG NON-SMOKER | 36 | |
Significant markers | N = 134 |
Table S22. Get Full Table List of top 10 genes differentially expressed by 'TOBACCOSMOKINGHISTORYINDICATOR'
ANOVA_P | Q | |
---|---|---|
GPR15|2838 | 6.602e-15 | 1.21e-10 |
DBF4B|80174 | 1.385e-09 | 2.54e-05 |
C20ORF103|24141 | 5.441e-09 | 9.96e-05 |
CASR|846 | 7.515e-09 | 0.000138 |
KNTC1|9735 | 8.424e-09 | 0.000154 |
TSPAN3|10099 | 1.225e-08 | 0.000224 |
RBM17|84991 | 1.303e-08 | 0.000238 |
MASTL|84930 | 1.391e-08 | 0.000255 |
CHEK1|1111 | 1.847e-08 | 0.000338 |
HPGD|3248 | 2.12e-08 | 0.000388 |
Figure S10. Get High-res Image As an example, this figure shows the association of GPR15|2838 to 'TOBACCOSMOKINGHISTORYINDICATOR'. P value = 6.6e-15 with ANOVA analysis.
![](V12ex.png)
Table S23. Basic characteristics of clinical feature: 'YEAROFTOBACCOSMOKINGONSET'
YEAROFTOBACCOSMOKINGONSET | Mean (SD) | 1965.19 (13) |
Significant markers | N = 2 | |
pos. correlated | 1 | |
neg. correlated | 1 |
Table S24. Get Full Table List of 2 genes significantly correlated to 'YEAROFTOBACCOSMOKINGONSET' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
ENTPD3|956 | -0.3578 | 8.798e-07 | 0.0161 |
GPR15|2838 | 0.3649 | 1.074e-06 | 0.0197 |
Figure S11. Get High-res Image As an example, this figure shows the association of ENTPD3|956 to 'YEAROFTOBACCOSMOKINGONSET'. P value = 8.8e-07 with Spearman correlation analysis. The straight line presents the best linear regression.
![](V13ex.png)
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Expresson data file = LUAD-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
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Clinical data file = LUAD-TP.clin.merged.picked.txt
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Number of patients = 354
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Number of genes = 18310
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Number of clinical features = 14
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
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
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
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
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.
This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.