Correlation between mRNAseq expression and clinical features
Lung Adenocarcinoma (BRONCHIOID)
07 February 2013  |  awg_luad__2013_02_07
Maintainer Information
Citation Information
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1PV6HGN
Overview
Introduction

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

Summary

Testing the association between 18243 genes and 14 clinical features across 89 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.

  • 14 genes correlated to 'GENDER'.

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

  • 12 genes correlated to 'HISTOLOGICAL.TYPE'.

    • CYFIP2|26999 ,  INSC|387755 ,  SPATA5|166378 ,  KIAA1279|26128 ,  NMNAT3|349565 ,  ...

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

    • SSX4|6759 ,  PRO0628|29053

  • 5 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • HOXC9|3225 ,  ADRA1B|147 ,  VCX|26609 ,  QRFP|347148 ,  CALML4|91860

  • 1 gene correlated to 'STOPPEDSMOKINGYEAR'.

    • GPR15|2838

  • 1 gene correlated to 'TOBACCOSMOKINGHISTORYINDICATOR'.

    • CBS|875

  • 12 genes correlated to 'YEAROFTOBACCOSMOKINGONSET'.

    • MYSM1|114803 ,  ZFC3H1|196441 ,  KIAA0831|22863 ,  PAN3|255967 ,  COL27A1|85301 ,  ...

  • No genes correlated to 'Time to Death', 'AGE', 'KARNOFSKY.PERFORMANCE.SCORE', 'PATHOLOGY.T', 'PATHOLOGY.N', 'TUMOR.STAGE', and 'NUMBERPACKYEARSSMOKED'.

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=0        
AGE Spearman correlation test   N=0        
GENDER t test N=14 male N=9 female N=5
KARNOFSKY PERFORMANCE SCORE Spearman correlation test   N=0        
HISTOLOGICAL TYPE ANOVA test N=12        
PATHOLOGY T Spearman correlation test   N=0        
PATHOLOGY N Spearman correlation test   N=0        
PATHOLOGICSPREAD(M) ANOVA test N=2        
TUMOR STAGE Spearman correlation test   N=0        
RADIATIONS RADIATION REGIMENINDICATION t test N=5 yes N=2 no N=3
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
STOPPEDSMOKINGYEAR Spearman correlation test N=1 higher stoppedsmokingyear N=1 lower stoppedsmokingyear N=0
TOBACCOSMOKINGHISTORYINDICATOR ANOVA test N=1        
YEAROFTOBACCOSMOKINGONSET Spearman correlation test N=12 higher yearoftobaccosmokingonset N=12 lower yearoftobaccosmokingonset N=0
Clinical variable #1: 'Time to Death'

No gene related to 'Time to Death'.

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

Time to Death Duration (Months) 0.1-224 (median=12.8)
  censored N = 62
  death N = 18
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

No gene related to 'AGE'.

Table S2.  Basic characteristics of clinical feature: 'AGE'

AGE Mean (SD) 67.61 (8.6)
  Significant markers N = 0
Clinical variable #3: 'GENDER'

14 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 64
  MALE 25
     
  Significant markers N = 14
  Higher in MALE 9
  Higher in FEMALE 5
List of top 10 genes differentially expressed by 'GENDER'

Table S4.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
XIST|7503 -29.32 3.178e-33 5.8e-29 0.9868
ZFY|7544 25.64 9.773e-31 1.78e-26 0.9972
PRKY|5616 21.48 1.623e-25 2.96e-21 0.9993
RPS4Y1|6192 21.07 5.121e-22 9.34e-18 0.9941
DDX3Y|8653 21.46 2.899e-21 5.29e-17 0.9969
TSIX|9383 -16.54 4.888e-17 8.91e-13 0.9974
KDM5D|8284 17.21 3.136e-15 5.72e-11 0.9953
NLGN4Y|22829 14.38 7.598e-15 1.39e-10 0.9873
USP9Y|8287 13.74 3.429e-09 6.25e-05 1
UTY|7404 12.04 3.681e-08 0.000671 0.9927

Figure S1.  Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 3.18e-33 with T-test analysis.

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

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

Table S5.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 81.82 (30)
  Score N
  0 1
  60 1
  80 1
  90 4
  100 4
     
  Significant markers N = 0
Clinical variable #5: 'HISTOLOGICAL.TYPE'

12 genes related to 'HISTOLOGICAL.TYPE'.

Table S6.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  LUNG ACINAR ADENOCARCINOMA 3
  LUNG ADENOCARCINOMA MIXED SUBTYPE 22
  LUNG ADENOCARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 49
  LUNG BRONCHIOLOALVEOLAR CARCINOMA MUCINOUS 3
  LUNG BRONCHIOLOALVEOLAR CARCINOMA NONMUCINOUS 8
  LUNG MICROPAPILLARY ADENOCARCINOMA 1
  LUNG MUCINOUS ADENOCARCINOMA 1
  LUNG PAPILLARY ADENOCARCINOMA 1
  MUCINOUS (COLLOID) ADENOCARCINOMA 1
     
  Significant markers N = 12
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S7.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
CYFIP2|26999 8.702e-11 1.59e-06
INSC|387755 1.791e-08 0.000327
SPATA5|166378 9.706e-08 0.00177
KIAA1279|26128 1.956e-07 0.00357
NMNAT3|349565 2.855e-07 0.00521
CD3D|915 5.945e-07 0.0108
B3GALT2|8707 8.022e-07 0.0146
DDX50|79009 1.05e-06 0.0191
GOLT1A|127845 1.064e-06 0.0194
PLAC8L1|153770 1.502e-06 0.0274

Figure S2.  Get High-res Image As an example, this figure shows the association of CYFIP2|26999 to 'HISTOLOGICAL.TYPE'. P value = 8.7e-11 with ANOVA analysis.

Clinical variable #6: 'PATHOLOGY.T'

No gene related to 'PATHOLOGY.T'.

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY.T'

PATHOLOGY.T Mean (SD) 1.72 (0.69)
  N
  T1 35
  T2 45
  T3 6
  T4 2
     
  Significant markers N = 0
Clinical variable #7: 'PATHOLOGY.N'

No gene related to 'PATHOLOGY.N'.

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

PATHOLOGY.N Mean (SD) 0.38 (0.69)
  N
  N0 63
  N1 12
  N2 10
     
  Significant markers N = 0
Clinical variable #8: 'PATHOLOGICSPREAD(M)'

2 genes related to 'PATHOLOGICSPREAD(M)'.

Table S10.  Basic characteristics of clinical feature: 'PATHOLOGICSPREAD(M)'

PATHOLOGICSPREAD(M) Labels N
  M0 63
  M1 2
  MX 19
     
  Significant markers N = 2
List of 2 genes differentially expressed by 'PATHOLOGICSPREAD(M)'

Table S11.  Get Full Table List of 2 genes differentially expressed by 'PATHOLOGICSPREAD(M)'

ANOVA_P Q
SSX4|6759 1.707e-07 0.00311
PRO0628|29053 2.602e-06 0.0475

Figure S3.  Get High-res Image As an example, this figure shows the association of SSX4|6759 to 'PATHOLOGICSPREAD(M)'. P value = 1.71e-07 with ANOVA analysis.

Clinical variable #9: 'TUMOR.STAGE'

No gene related to 'TUMOR.STAGE'.

Table S12.  Basic characteristics of clinical feature: 'TUMOR.STAGE'

TUMOR.STAGE Mean (SD) 1.51 (0.78)
  N
  Stage 1 55
  Stage 2 19
  Stage 3 9
  Stage 4 2
     
  Significant markers N = 0
Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

5 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S13.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 6
  YES 83
     
  Significant markers N = 5
  Higher in YES 2
  Higher in NO 3
List of 5 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S14.  Get Full Table List of 5 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
HOXC9|3225 -10.78 2.725e-12 4.86e-08 0.9067
ADRA1B|147 -8.74 5.46e-09 9.73e-05 0.9217
VCX|26609 -8.91 1.084e-08 0.000193 0.9375
QRFP|347148 5.57 1.094e-06 0.0195 0.7908
CALML4|91860 5.89 1.434e-06 0.0256 0.7631

Figure S4.  Get High-res Image As an example, this figure shows the association of HOXC9|3225 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 2.72e-12 with T-test analysis.

Clinical variable #11: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

Table S15.  Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED Mean (SD) 32.76 (24)
  Significant markers N = 0
Clinical variable #12: 'STOPPEDSMOKINGYEAR'

One gene related to 'STOPPEDSMOKINGYEAR'.

Table S16.  Basic characteristics of clinical feature: 'STOPPEDSMOKINGYEAR'

STOPPEDSMOKINGYEAR Mean (SD) 1989.74 (14)
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene significantly correlated to 'STOPPEDSMOKINGYEAR' by Spearman correlation test

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

SpearmanCorr corrP Q
GPR15|2838 0.6185 2.181e-06 0.0398

Figure S5.  Get High-res Image As an example, this figure shows the association of GPR15|2838 to 'STOPPEDSMOKINGYEAR'. P value = 2.18e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #13: 'TOBACCOSMOKINGHISTORYINDICATOR'

One gene related to 'TOBACCOSMOKINGHISTORYINDICATOR'.

Table S18.  Basic characteristics of clinical feature: 'TOBACCOSMOKINGHISTORYINDICATOR'

TOBACCOSMOKINGHISTORYINDICATOR Labels N
  CURRENT REFORMED SMOKER FOR < OR = 15 YEARS 25
  CURRENT REFORMED SMOKER FOR > 15 YEARS 32
  CURRENT SMOKER 10
  LIFELONG NON-SMOKER 19
     
  Significant markers N = 1
List of one gene differentially expressed by 'TOBACCOSMOKINGHISTORYINDICATOR'

Table S19.  Get Full Table List of one gene differentially expressed by 'TOBACCOSMOKINGHISTORYINDICATOR'

ANOVA_P Q
CBS|875 4.621e-07 0.00843

Figure S6.  Get High-res Image As an example, this figure shows the association of CBS|875 to 'TOBACCOSMOKINGHISTORYINDICATOR'. P value = 4.62e-07 with ANOVA analysis.

Clinical variable #14: 'YEAROFTOBACCOSMOKINGONSET'

12 genes related to 'YEAROFTOBACCOSMOKINGONSET'.

Table S20.  Basic characteristics of clinical feature: 'YEAROFTOBACCOSMOKINGONSET'

YEAROFTOBACCOSMOKINGONSET Mean (SD) 1960.95 (12)
  Significant markers N = 12
  pos. correlated 12
  neg. correlated 0
List of top 10 genes significantly correlated to 'YEAROFTOBACCOSMOKINGONSET' by Spearman correlation test

Table S21.  Get Full Table List of top 10 genes significantly correlated to 'YEAROFTOBACCOSMOKINGONSET' by Spearman correlation test

SpearmanCorr corrP Q
MYSM1|114803 0.7484 7.965e-09 0.000145
ZFC3H1|196441 0.719 5.625e-08 0.00103
KIAA0831|22863 0.7054 1.276e-07 0.00233
PAN3|255967 0.7001 1.745e-07 0.00318
COL27A1|85301 0.6887 3.303e-07 0.00602
BTAF1|9044 0.6858 3.882e-07 0.00708
AGAP5|729092 0.6839 4.3e-07 0.00784
CLDN20|49861 0.7091 1.293e-06 0.0236
LRIG2|9860 0.6561 1.782e-06 0.0325
SENP7|57337 0.6555 1.835e-06 0.0335

Figure S7.  Get High-res Image As an example, this figure shows the association of MYSM1|114803 to 'YEAROFTOBACCOSMOKINGONSET'. P value = 7.97e-09 with Spearman correlation analysis. The straight line presents the best linear regression.

Methods & Data
Input
  • Expresson data file = BRONCHIOID.uncv2.mRNAseq_RSEM_normalized_log2.txt

  • Clinical data file = BRONCHIOID.clin.merged.picked.txt

  • Number of patients = 89

  • Number of genes = 18243

  • 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)