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 18249 genes and 15 clinical features across 223 samples, statistically thresholded by Q value < 0.05, 12 clinical features related to at least one genes.

  • 6 genes correlated to 'Time to Death'.

    • UCN2|90226 ,  DKK1|22943 ,  IRX5|10265 ,  FAM189A2|9413 ,  CDH26|60437 ,  ...

  • 54 genes correlated to 'GENDER'.

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

  • 2 genes correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

    • PSMA5|5686 ,  PRPF8|10594

  • 16 genes correlated to 'HISTOLOGICAL.TYPE'.

    • DPCR1|135656 ,  CDHR2|54825 ,  REG4|83998 ,  B3GALT5|10317 ,  ODF2L|57489 ,  ...

  • 7 genes correlated to 'PATHOLOGY.T'.

    • FAM125B|89853 ,  APBB1|322 ,  MAL|4118 ,  PPIF|10105 ,  CADM3|57863 ,  ...

  • 2 genes correlated to 'PATHOLOGY.N'.

    • FAM117A|81558 ,  RARS|5917

  • 25 genes correlated to 'PATHOLOGICSPREAD(M)'.

    • AKAP5|9495 ,  MLL5|55904 ,  RNF187|149603 ,  MLST8|64223 ,  ZNF37B|100129482 ,  ...

  • 1 gene correlated to 'TUMOR.STAGE'.

    • ST6GAL1|6480

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

    • KCNU1|157855

  • 1 gene correlated to 'NUMBERPACKYEARSSMOKED'.

    • LOC723809|723809

  • 1 gene correlated to 'STOPPEDSMOKINGYEAR'.

    • GPR15|2838

  • 3 genes correlated to 'TOBACCOSMOKINGHISTORYINDICATOR'.

    • GPR15|2838 ,  CASR|846 ,  RBM17|84991

  • No genes correlated to 'AGE', 'NEOADJUVANT.THERAPY', and 'YEAROFTOBACCOSMOKINGONSET'.

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=6 shorter survival N=3 longer survival N=3
AGE Spearman correlation test   N=0        
GENDER t test N=54 male N=22 female N=32
KARNOFSKY PERFORMANCE SCORE Spearman correlation test N=2 higher score N=1 lower score N=1
HISTOLOGICAL TYPE ANOVA test N=16        
PATHOLOGY T Spearman correlation test N=7 higher pT N=3 lower pT N=4
PATHOLOGY N Spearman correlation test N=2 higher pN N=1 lower pN N=1
PATHOLOGICSPREAD(M) ANOVA test N=25        
TUMOR STAGE Spearman correlation test N=1 higher stage N=0 lower stage N=1
RADIATIONS RADIATION REGIMENINDICATION t test N=1 yes N=0 no N=1
NEOADJUVANT THERAPY t test   N=0        
NUMBERPACKYEARSSMOKED Spearman correlation test N=1 higher numberpackyearssmoked N=0 lower numberpackyearssmoked N=1
STOPPEDSMOKINGYEAR Spearman correlation test N=1 higher stoppedsmokingyear N=1 lower stoppedsmokingyear N=0
TOBACCOSMOKINGHISTORYINDICATOR ANOVA test N=3        
YEAROFTOBACCOSMOKINGONSET Spearman correlation test   N=0        
Clinical variable #1: 'Time to Death'

6 genes related to 'Time to Death'.

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

Time to Death Duration (Months) 0-224 (median=13.9)
  censored N = 133
  death N = 62
     
  Significant markers N = 6
  associated with shorter survival 3
  associated with longer survival 3
List of 6 genes significantly associated with 'Time to Death' by Cox regression test

Table S2.  Get Full Table List of 6 genes significantly associated with 'Time to Death' by Cox regression test

HazardRatio Wald_P Q C_index
UCN2|90226 1.49 4.016e-08 0.00073 0.7
DKK1|22943 1.28 7.028e-08 0.0013 0.755
IRX5|10265 0.74 1.229e-07 0.0022 0.326
FAM189A2|9413 0.74 1.543e-06 0.028 0.346
CDH26|60437 0.77 1.965e-06 0.036 0.299
MFSD2B|388931 1.87 2.148e-06 0.039 0.695

Figure S1.  Get High-res Image As an example, this figure shows the association of UCN2|90226 to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 4.02e-08 with univariate Cox regression analysis using continuous log-2 expression values.

Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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

AGE Mean (SD) 65.93 (9.7)
  Significant markers N = 0
Clinical variable #3: 'GENDER'

54 genes related to 'GENDER'.

Table S4.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 125
  MALE 98
     
  Significant markers N = 54
  Higher in MALE 22
  Higher in FEMALE 32
List of top 10 genes differentially expressed by 'GENDER'

Table S5.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
PRKY|5616 35.89 1.073e-88 1.96e-84 0.999
XIST|7503 -36.24 1.152e-71 2.1e-67 0.9925
ZFY|7544 37.11 2.612e-58 4.77e-54 0.9967
RPS4Y1|6192 35.56 6.881e-54 1.26e-49 0.9952
DDX3Y|8653 32.81 2.382e-38 4.34e-34 0.9967
NLGN4Y|22829 21.31 3.755e-31 6.85e-27 0.9896
TSIX|9383 -16.05 5.858e-25 1.07e-20 0.9919
USP9Y|8287 26.21 1.425e-24 2.6e-20 0.9996
KDM5D|8284 24.58 1.357e-22 2.48e-18 0.9961
ZRSR2|8233 -9.35 1.528e-17 2.79e-13 0.8316

Figure S2.  Get High-res Image As an example, this figure shows the association of PRKY|5616 to 'GENDER'. P value = 1.07e-88 with T-test analysis.

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

2 genes related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S6.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 67.06 (40)
  Significant markers N = 2
  pos. correlated 1
  neg. correlated 1
List of 2 genes significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

Table S7.  Get Full Table List of 2 genes significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

SpearmanCorr corrP Q
PSMA5|5686 -0.8903 1.683e-06 0.0307
PRPF8|10594 0.8878 1.98e-06 0.0361

Figure S3.  Get High-res Image As an example, this figure shows the association of PSMA5|5686 to 'KARNOFSKY.PERFORMANCE.SCORE'. P value = 1.68e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #5: 'HISTOLOGICAL.TYPE'

16 genes related to 'HISTOLOGICAL.TYPE'.

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

HISTOLOGICAL.TYPE Labels N
  LUNG ACINAR ADENOCARCINOMA 5
  LUNG ADENOCARCINOMA MIXED SUBTYPE 54
  LUNG ADENOCARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 136
  LUNG BRONCHIOLOALVEOLAR CARCINOMA MUCINOUS 3
  LUNG BRONCHIOLOALVEOLAR CARCINOMA NONMUCINOUS 10
  LUNG MICROPAPILLARY ADENOCARCINOMA 2
  LUNG MUCINOUS ADENOCARCINOMA 1
  LUNG PAPILLARY ADENOCARCINOMA 8
  MUCINOUS (COLLOID) ADENOCARCINOMA 4
     
  Significant markers N = 16
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
DPCR1|135656 9.875e-10 1.8e-05
CDHR2|54825 8.713e-08 0.00159
REG4|83998 1.277e-07 0.00233
B3GALT5|10317 1.409e-07 0.00257
ODF2L|57489 2.613e-07 0.00477
LPCAT4|254531 2.799e-07 0.00511
ELOVL5|60481 2.807e-07 0.00512
TPRG1|285386 2.81e-07 0.00513
INSC|387755 3.164e-07 0.00577
MYO1A|4640 5.807e-07 0.0106

Figure S4.  Get High-res Image As an example, this figure shows the association of DPCR1|135656 to 'HISTOLOGICAL.TYPE'. P value = 9.88e-10 with ANOVA analysis.

Clinical variable #6: 'PATHOLOGY.T'

7 genes related to 'PATHOLOGY.T'.

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

PATHOLOGY.T Mean (SD) 1.94 (0.79)
  N
  T1 60
  T2 130
  T3 17
  T4 15
     
  Significant markers N = 7
  pos. correlated 3
  neg. correlated 4
List of 7 genes significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

Table S11.  Get Full Table List of 7 genes significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

SpearmanCorr corrP Q
FAM125B|89853 -0.336 2.932e-07 0.00535
APBB1|322 -0.3218 9.636e-07 0.0176
MAL|4118 -0.3177 1.342e-06 0.0245
PPIF|10105 0.3177 1.352e-06 0.0247
CADM3|57863 -0.316 1.548e-06 0.0282
ATP5B|506 0.3108 2.328e-06 0.0425
MRPS35|60488 0.3099 2.511e-06 0.0458

Figure S5.  Get High-res Image As an example, this figure shows the association of FAM125B|89853 to 'PATHOLOGY.T'. P value = 2.93e-07 with Spearman correlation analysis.

Clinical variable #7: 'PATHOLOGY.N'

2 genes related to 'PATHOLOGY.N'.

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

PATHOLOGY.N Mean (SD) 0.59 (0.81)
  N
  N0 132
  N1 43
  N2 41
  N3 1
     
  Significant markers N = 2
  pos. correlated 1
  neg. correlated 1
List of 2 genes significantly correlated to 'PATHOLOGY.N' by Spearman correlation test

Table S13.  Get Full Table List of 2 genes significantly correlated to 'PATHOLOGY.N' by Spearman correlation test

SpearmanCorr corrP Q
FAM117A|81558 -0.3267 8.605e-07 0.0157
RARS|5917 0.3208 1.387e-06 0.0253

Figure S6.  Get High-res Image As an example, this figure shows the association of FAM117A|81558 to 'PATHOLOGY.N'. P value = 8.61e-07 with Spearman correlation analysis.

Clinical variable #8: 'PATHOLOGICSPREAD(M)'

25 genes related to 'PATHOLOGICSPREAD(M)'.

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

PATHOLOGICSPREAD(M) Labels N
  M0 159
  M1 8
  MX 51
     
  Significant markers N = 25
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
AKAP5|9495 2.481e-08 0.000453
MLL5|55904 8.265e-08 0.00151
RNF187|149603 1.604e-07 0.00293
MLST8|64223 1.952e-07 0.00356
ZNF37B|100129482 2.378e-07 0.00434
PPIG|9360 4.809e-07 0.00877
C12ORF57|113246 4.952e-07 0.00903
ANKRD12|23253 5.982e-07 0.0109
MRPS34|65993 6.175e-07 0.0113
FAM195A|84331 7.937e-07 0.0145

Figure S7.  Get High-res Image As an example, this figure shows the association of AKAP5|9495 to 'PATHOLOGICSPREAD(M)'. P value = 2.48e-08 with ANOVA analysis.

Clinical variable #9: 'TUMOR.STAGE'

One gene related to 'TUMOR.STAGE'.

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

TUMOR.STAGE Mean (SD) 1.77 (0.93)
  N
  Stage 1 115
  Stage 2 47
  Stage 3 47
  Stage 4 9
     
  Significant markers N = 1
  pos. correlated 0
  neg. correlated 1
List of one gene significantly correlated to 'TUMOR.STAGE' by Spearman correlation test

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

SpearmanCorr corrP Q
ST6GAL1|6480 -0.3154 2.008e-06 0.0367

Figure S8.  Get High-res Image As an example, this figure shows the association of ST6GAL1|6480 to 'TUMOR.STAGE'. P value = 2.01e-06 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 15
  YES 208
     
  Significant markers N = 1
  Higher in YES 0
  Higher in NO 1
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
KCNU1|157855 -8.12 1.24e-10 2.26e-06 0.8209

Figure S9.  Get High-res Image As an example, this figure shows the association of KCNU1|157855 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 1.24e-10 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 36
  YES 187
     
  Significant markers N = 0
Clinical variable #12: 'NUMBERPACKYEARSSMOKED'

One gene related to 'NUMBERPACKYEARSSMOKED'.

Table S21.  Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED Mean (SD) 40.04 (27)
  Significant markers N = 1
  pos. correlated 0
  neg. correlated 1
List of one gene significantly correlated to 'NUMBERPACKYEARSSMOKED' by Spearman correlation test

Table S22.  Get Full Table List of one gene significantly correlated to 'NUMBERPACKYEARSSMOKED' by Spearman correlation test

SpearmanCorr corrP Q
LOC723809|723809 -0.4 5.177e-07 0.00945

Figure S10.  Get High-res Image As an example, this figure shows the association of LOC723809|723809 to 'NUMBERPACKYEARSSMOKED'. P value = 5.18e-07 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #13: 'STOPPEDSMOKINGYEAR'

One gene related to 'STOPPEDSMOKINGYEAR'.

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

STOPPEDSMOKINGYEAR Mean (SD) 1991.76 (14)
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene significantly correlated to 'STOPPEDSMOKINGYEAR' by Spearman correlation test

Table S24.  Get Full Table List of one gene significantly correlated to 'STOPPEDSMOKINGYEAR' by Spearman correlation test

SpearmanCorr corrP Q
GPR15|2838 0.6551 1.414e-13 2.58e-09

Figure S11.  Get High-res Image As an example, this figure shows the association of GPR15|2838 to 'STOPPEDSMOKINGYEAR'. P value = 1.41e-13 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #14: 'TOBACCOSMOKINGHISTORYINDICATOR'

3 genes related to 'TOBACCOSMOKINGHISTORYINDICATOR'.

Table S25.  Basic characteristics of clinical feature: 'TOBACCOSMOKINGHISTORYINDICATOR'

TOBACCOSMOKINGHISTORYINDICATOR Labels N
  CURRENT REFORMED SMOKER FOR < OR = 15 YEARS 69
  CURRENT REFORMED SMOKER FOR > 15 YEARS 67
  CURRENT SMOKER 45
  LIFELONG NON-SMOKER 32
     
  Significant markers N = 3
List of 3 genes differentially expressed by 'TOBACCOSMOKINGHISTORYINDICATOR'

Table S26.  Get Full Table List of 3 genes differentially expressed by 'TOBACCOSMOKINGHISTORYINDICATOR'

ANOVA_P Q
GPR15|2838 6.274e-15 1.14e-10
CASR|846 2.358e-07 0.0043
RBM17|84991 1.543e-06 0.0282

Figure S12.  Get High-res Image As an example, this figure shows the association of GPR15|2838 to 'TOBACCOSMOKINGHISTORYINDICATOR'. P value = 6.27e-15 with ANOVA analysis.

Clinical variable #15: 'YEAROFTOBACCOSMOKINGONSET'

No gene related to 'YEAROFTOBACCOSMOKINGONSET'.

Table S27.  Basic characteristics of clinical feature: 'YEAROFTOBACCOSMOKINGONSET'

YEAROFTOBACCOSMOKINGONSET Mean (SD) 1961.99 (13)
  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 = 223

  • Number of genes = 18249

  • Number of clinical features = 15

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)
Copyright © 2012 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle