Correlation between mRNAseq expression and clinical features
Lung Adenocarcinoma (Primary solid tumor)
21 April 2013  |  analyses__2013_04_21
Maintainer Information
Citation Information
doi:10.7908/C1NS0RTR
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Lung Adenocarcinoma (Primary solid tumor cohort) - 21 April 2013: Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1NS0RTR
Overview
Introduction

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

Summary

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.

  • 10 genes correlated to 'Time to Death'.

    • ESYT3|83850 ,  UCN2|90226 ,  MYLIP|29116 ,  DKK1|22943 ,  LDLRAD3|143458 ,  ...

  • 3 genes correlated to 'AGE'.

    • HSD17B2|3294 ,  GPR15|2838 ,  AHRR|57491

  • 85 genes correlated to 'GENDER'.

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

  • 31 genes correlated to 'HISTOLOGICAL.TYPE'.

    • CREB3L3|84699 ,  A4GNT|51146 ,  MIA|8190 ,  REG4|83998 ,  CRH|1392 ,  ...

  • 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

  • 79 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 ,  ...

  • 2 genes correlated to 'NUMBERPACKYEARSSMOKED'.

    • LOC723809|723809 ,  LHFPL3|375612

  • 134 genes correlated to 'TOBACCOSMOKINGHISTORYINDICATOR'.

    • GPR15|2838 ,  DBF4B|80174 ,  C20ORF103|24141 ,  CASR|846 ,  KNTC1|9735 ,  ...

  • 2 genes correlated to 'YEAROFTOBACCOSMOKINGONSET'.

    • ENTPD3|956 ,  GPR15|2838

  • No genes correlated to 'KARNOFSKY.PERFORMANCE.SCORE', 'RADIATIONS.RADIATION.REGIMENINDICATION', and 'COMPLETENESS.OF.RESECTION'.

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=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        
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) 0-224 (median=8.5)
  censored N = 234
  death N = 81
     
  Significant markers N = 10
  associated with shorter survival 6
  associated with longer survival 4
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
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.

Clinical variable #2: 'AGE'

3 genes related to 'AGE'.

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
List of 3 genes significantly correlated to 'AGE' by Spearman correlation test

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.

Clinical variable #3: 'GENDER'

85 genes related to 'GENDER'.

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
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 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.

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) 75.86 (32)
  Significant markers N = 0
Clinical variable #5: 'HISTOLOGICAL.TYPE'

31 genes related to 'HISTOLOGICAL.TYPE'.

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
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
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.

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 168
  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 -0.318 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.

Clinical variable #7: 'PATHOLOGY.N'

3 genes related to 'PATHOLOGY.N'.

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

PATHOLOGY.N Mean (SD) 0.58 (0.79)
  N
  N0 171
  N1 59
  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 0.3131 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.

Clinical variable #8: 'PATHOLOGICSPREAD(M)'

79 genes related to 'PATHOLOGICSPREAD(M)'.

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

PATHOLOGICSPREAD(M) Labels N
  M0 200
  M1 16
  MX 64
     
  Significant markers N = 79
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 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.

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 1 148
  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 -0.2929 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.

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

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
Clinical variable #11: 'NUMBERPACKYEARSSMOKED'

2 genes related to 'NUMBERPACKYEARSSMOKED'.

Table S19.  Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED Mean (SD) 40.66 (27)
  Significant markers N = 2
  pos. correlated 0
  neg. correlated 2
List of 2 genes significantly correlated to 'NUMBERPACKYEARSSMOKED' by Spearman correlation test

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.

Clinical variable #12: 'TOBACCOSMOKINGHISTORYINDICATOR'

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
List of top 10 genes differentially expressed by 'TOBACCOSMOKINGHISTORYINDICATOR'

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.

Clinical variable #13: 'YEAROFTOBACCOSMOKINGONSET'

2 genes related to 'YEAROFTOBACCOSMOKINGONSET'.

Table S23.  Basic characteristics of clinical feature: 'YEAROFTOBACCOSMOKINGONSET'

YEAROFTOBACCOSMOKINGONSET Mean (SD) 1965.19 (13)
  Significant markers N = 2
  pos. correlated 1
  neg. correlated 1
List of 2 genes significantly correlated to 'YEAROFTOBACCOSMOKINGONSET' by Spearman correlation test

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.

Clinical variable #14: 'COMPLETENESS.OF.RESECTION'

No gene related to 'COMPLETENESS.OF.RESECTION'.

Table S25.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 203
  R1 9
  R2 4
  RX 12
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 354

  • Number of genes = 18310

  • Number of clinical features = 14

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.

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)
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