Correlation between RPPA expression and clinical features
Lung Adenocarcinoma (MOLECULAR_NONSMOKER)
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 RPPA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1Z31WRS
Overview
Introduction

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

Summary

Testing the association between 174 genes and 14 clinical features across 66 samples, statistically thresholded by Q value < 0.05, 4 clinical features related to at least one genes.

  • 1 gene correlated to 'HISTOLOGICAL.TYPE'.

    • BCL2|BCL-2-R-C

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

    • BAX|BAX-R-V ,  GAB2|GAB2-R-V ,  RAF1|C-RAF-R-V ,  SHC1|SHC_PY317-R-C

  • 1 gene correlated to 'TOBACCOSMOKINGHISTORYINDICATOR'.

    • CHEK2|CHK2_PT68-R-C

  • 1 gene correlated to 'YEAROFTOBACCOSMOKINGONSET'.

    • YWHAE|14-3-3_EPSILON-M-C

  • No genes correlated to 'Time to Death', 'AGE', 'GENDER', 'KARNOFSKY.PERFORMANCE.SCORE', 'PATHOLOGY.T', 'PATHOLOGY.N', 'PATHOLOGICSPREAD(M)', 'TUMOR.STAGE', 'NUMBERPACKYEARSSMOKED', and 'STOPPEDSMOKINGYEAR'.

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=0        
KARNOFSKY PERFORMANCE SCORE Spearman correlation test   N=0        
HISTOLOGICAL TYPE ANOVA test N=1        
PATHOLOGY T Spearman correlation test   N=0        
PATHOLOGY N Spearman correlation test   N=0        
PATHOLOGICSPREAD(M) ANOVA test   N=0        
TUMOR STAGE Spearman correlation test   N=0        
RADIATIONS RADIATION REGIMENINDICATION t test N=4 yes N=3 no N=1
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
STOPPEDSMOKINGYEAR Spearman correlation test   N=0        
TOBACCOSMOKINGHISTORYINDICATOR ANOVA test N=1        
YEAROFTOBACCOSMOKINGONSET Spearman correlation test N=1 higher yearoftobaccosmokingonset N=0 lower yearoftobaccosmokingonset N=1
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=13.2)
  censored N = 39
  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) 65.98 (9.8)
  Significant markers N = 0
Clinical variable #3: 'GENDER'

No gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 38
  MALE 28
     
  Significant markers N = 0
Clinical variable #4: 'KARNOFSKY.PERFORMANCE.SCORE'

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

Table S4.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 32.5 (38)
  Score N
  0 2
  60 1
  70 1
     
  Significant markers N = 0
Clinical variable #5: 'HISTOLOGICAL.TYPE'

One gene related to 'HISTOLOGICAL.TYPE'.

Table S5.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  LUNG ACINAR ADENOCARCINOMA 3
  LUNG ADENOCARCINOMA MIXED SUBTYPE 14
  LUNG ADENOCARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 38
  LUNG BRONCHIOLOALVEOLAR CARCINOMA MUCINOUS 3
  LUNG BRONCHIOLOALVEOLAR CARCINOMA NONMUCINOUS 2
  LUNG MICROPAPILLARY ADENOCARCINOMA 1
  LUNG MUCINOUS ADENOCARCINOMA 1
  LUNG PAPILLARY ADENOCARCINOMA 2
  MUCINOUS (COLLOID) ADENOCARCINOMA 2
     
  Significant markers N = 1
List of one gene differentially expressed by 'HISTOLOGICAL.TYPE'

Table S6.  Get Full Table List of one gene differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
BCL2|BCL-2-R-C 8.196e-06 0.00143

Figure S1.  Get High-res Image As an example, this figure shows the association of BCL2|BCL-2-R-C to 'HISTOLOGICAL.TYPE'. P value = 8.2e-06 with ANOVA analysis.

Clinical variable #6: 'PATHOLOGY.T'

No gene related to 'PATHOLOGY.T'.

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY.T'

PATHOLOGY.T Mean (SD) 1.94 (0.73)
  N
  T1 16
  T2 40
  T3 6
  T4 3
     
  Significant markers N = 0
Clinical variable #7: 'PATHOLOGY.N'

No gene related to 'PATHOLOGY.N'.

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY.N'

PATHOLOGY.N Mean (SD) 0.64 (0.82)
  N
  N0 37
  N1 13
  N2 14
     
  Significant markers N = 0
Clinical variable #8: 'PATHOLOGICSPREAD(M)'

No gene related to 'PATHOLOGICSPREAD(M)'.

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGICSPREAD(M)'

PATHOLOGICSPREAD(M) Labels N
  M0 48
  M1 3
  MX 13
     
  Significant markers N = 0
Clinical variable #9: 'TUMOR.STAGE'

No gene related to 'TUMOR.STAGE'.

Table S10.  Basic characteristics of clinical feature: 'TUMOR.STAGE'

TUMOR.STAGE Mean (SD) 1.84 (0.95)
  N
  Stage 1 31
  Stage 2 14
  Stage 3 15
  Stage 4 3
     
  Significant markers N = 0
Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S11.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 3
  YES 63
     
  Significant markers N = 4
  Higher in YES 3
  Higher in NO 1
List of 4 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S12.  Get Full Table List of 4 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
BAX|BAX-R-V 5.42 7.753e-06 0.00135 0.7354
GAB2|GAB2-R-V 4.87 8.225e-05 0.0142 0.8148
RAF1|C-RAF-R-V 7.14 0.0001775 0.0305 0.9365
SHC1|SHC_PY317-R-C -4.53 0.000291 0.0498 0.8042

Figure S2.  Get High-res Image As an example, this figure shows the association of BAX|BAX-R-V to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 7.75e-06 with T-test analysis.

Clinical variable #11: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

Table S13.  Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED Mean (SD) 34.17 (34)
  Significant markers N = 0
Clinical variable #12: 'STOPPEDSMOKINGYEAR'

No gene related to 'STOPPEDSMOKINGYEAR'.

Table S14.  Basic characteristics of clinical feature: 'STOPPEDSMOKINGYEAR'

STOPPEDSMOKINGYEAR Mean (SD) 1988.89 (14)
  Significant markers N = 0
Clinical variable #13: 'TOBACCOSMOKINGHISTORYINDICATOR'

One gene related to 'TOBACCOSMOKINGHISTORYINDICATOR'.

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

TOBACCOSMOKINGHISTORYINDICATOR Labels N
  CURRENT REFORMED SMOKER FOR < OR = 15 YEARS 16
  CURRENT REFORMED SMOKER FOR > 15 YEARS 18
  CURRENT SMOKER 6
  LIFELONG NON-SMOKER 23
     
  Significant markers N = 1
List of one gene differentially expressed by 'TOBACCOSMOKINGHISTORYINDICATOR'

Table S16.  Get Full Table List of one gene differentially expressed by 'TOBACCOSMOKINGHISTORYINDICATOR'

ANOVA_P Q
CHEK2|CHK2_PT68-R-C 2.885e-05 0.00502

Figure S3.  Get High-res Image As an example, this figure shows the association of CHEK2|CHK2_PT68-R-C to 'TOBACCOSMOKINGHISTORYINDICATOR'. P value = 2.88e-05 with ANOVA analysis.

Clinical variable #14: 'YEAROFTOBACCOSMOKINGONSET'

One gene related to 'YEAROFTOBACCOSMOKINGONSET'.

Table S17.  Basic characteristics of clinical feature: 'YEAROFTOBACCOSMOKINGONSET'

YEAROFTOBACCOSMOKINGONSET Mean (SD) 1960.77 (12)
  Significant markers N = 1
  pos. correlated 0
  neg. correlated 1
List of one gene significantly correlated to 'YEAROFTOBACCOSMOKINGONSET' by Spearman correlation test

Table S18.  Get Full Table List of one gene significantly correlated to 'YEAROFTOBACCOSMOKINGONSET' by Spearman correlation test

SpearmanCorr corrP Q
YWHAE|14-3-3_EPSILON-M-C -0.7882 1.321e-05 0.0023

Figure S4.  Get High-res Image As an example, this figure shows the association of YWHAE|14-3-3_EPSILON-M-C to 'YEAROFTOBACCOSMOKINGONSET'. P value = 1.32e-05 with Spearman correlation analysis. The straight line presents the best linear regression.

Methods & Data
Input
  • Expresson data file = MOLECULAR_NONSMOKER.rppa.txt

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

  • Number of patients = 66

  • Number of genes = 174

  • 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)