Correlation between RPPA expression and clinical features
Lung Adenocarcinoma (Primary solid tumor)
21 April 2013  |  analyses__2013_04_21
Maintainer Information
Citation Information
doi:10.7908/C1X63JWX
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 RPPA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1X63JWX
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 237 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

  • 2 genes correlated to 'AGE'.

    • PTGS2|COX-2-R-C ,  ARID1A|ARID1A-M-V

  • 1 gene correlated to 'GENDER'.

    • CLDN7|CLAUDIN-7-R-V

  • 9 genes correlated to 'HISTOLOGICAL.TYPE'.

    • PARP1|PARP_CLEAVED-M-C ,  ERCC1|ERCC1-M-C ,  CASP8|CASPASE-8-M-C ,  MET|C-MET-M-C ,  RB1|RB-M-V ,  ...

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

    • EGFR|EGFR_PY1173-R-C ,  TP53|P53-R-V

  • 10 genes correlated to 'TOBACCOSMOKINGHISTORYINDICATOR'.

    • EIF4EBP1|4E-BP1-R-V ,  EIF4EBP1|4E-BP1_PT70-R-C ,  EGFR|EGFR_PY1068-R-V ,  CHEK1|CHK1-R-C ,  AKT1 AKT2 AKT3|AKT_PS473-R-V ,  ...

  • No genes correlated to 'Time to Death', 'KARNOFSKY.PERFORMANCE.SCORE', 'PATHOLOGY.T', 'PATHOLOGY.N', 'TUMOR.STAGE', 'RADIATIONS.RADIATION.REGIMENINDICATION', 'NUMBERPACKYEARSSMOKED', 'YEAROFTOBACCOSMOKINGONSET', 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=0        
AGE Spearman correlation test N=2 older N=0 younger N=2
GENDER t test N=1 male N=1 female N=0
KARNOFSKY PERFORMANCE SCORE Spearman correlation test   N=0        
HISTOLOGICAL TYPE ANOVA test N=9        
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=0        
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
TOBACCOSMOKINGHISTORYINDICATOR ANOVA test N=10        
YEAROFTOBACCOSMOKINGONSET Spearman correlation test   N=0        
COMPLETENESS OF RESECTION ANOVA test   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) 0-224 (median=12.2)
  censored N = 148
  death N = 66
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

2 genes related to 'AGE'.

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

AGE Mean (SD) 64.81 (9.8)
  Significant markers N = 2
  pos. correlated 0
  neg. correlated 2
List of 2 genes significantly correlated to 'AGE' by Spearman correlation test

Table S3.  Get Full Table List of 2 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
PTGS2|COX-2-R-C -0.2924 1.251e-05 0.00218
ARID1A|ARID1A-M-V -0.2464 0.0002553 0.0442

Figure S1.  Get High-res Image As an example, this figure shows the association of PTGS2|COX-2-R-C to 'AGE'. P value = 1.25e-05 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'GENDER'

One gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 131
  MALE 106
     
  Significant markers N = 1
  Higher in MALE 1
  Higher in FEMALE 0
List of one gene differentially expressed by 'GENDER'

Table S5.  Get Full Table List of one gene differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
CLDN7|CLAUDIN-7-R-V 3.86 0.0001598 0.0278 0.6072

Figure S2.  Get High-res Image As an example, this figure shows the association of CLDN7|CLAUDIN-7-R-V to 'GENDER'. P value = 0.00016 with T-test analysis.

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

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

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

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 69.05 (35)
  Significant markers N = 0
Clinical variable #5: 'HISTOLOGICAL.TYPE'

9 genes related to 'HISTOLOGICAL.TYPE'.

Table S7.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  LUNG ACINAR ADENOCARCINOMA 6
  LUNG ADENOCARCINOMA MIXED SUBTYPE 52
  LUNG ADENOCARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 151
  LUNG BRONCHIOLOALVEOLAR CARCINOMA MUCINOUS 3
  LUNG BRONCHIOLOALVEOLAR CARCINOMA NONMUCINOUS 10
  LUNG CLEAR CELL ADENOCARCINOMA 1
  LUNG MICROPAPILLARY ADENOCARCINOMA 2
  LUNG MUCINOUS ADENOCARCINOMA 2
  LUNG PAPILLARY ADENOCARCINOMA 6
  LUNG SOLID PATTERN PREDOMINANT ADENOCARCINOMA 1
  MUCINOUS (COLLOID) ADENOCARCINOMA 3
     
  Significant markers N = 9
List of 9 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S8.  Get Full Table List of 9 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
PARP1|PARP_CLEAVED-M-C 1.357e-07 2.36e-05
ERCC1|ERCC1-M-C 1.598e-07 2.77e-05
CASP8|CASPASE-8-M-C 2.088e-07 3.59e-05
MET|C-MET-M-C 6.775e-07 0.000116
RB1|RB-M-V 1.155e-06 0.000196
SNAI2|SNAIL-M-C 3.752e-06 0.000634
C12ORF5|TIGAR-R-V 4.014e-05 0.00674
DIABLO|SMAC-M-V 8.65e-05 0.0144
FOXO3|FOXO3A-R-C 0.0001199 0.0199

Figure S3.  Get High-res Image As an example, this figure shows the association of PARP1|PARP_CLEAVED-M-C to 'HISTOLOGICAL.TYPE'. P value = 1.36e-07 with ANOVA analysis.

Clinical variable #6: 'PATHOLOGY.T'

No gene related to 'PATHOLOGY.T'.

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY.T'

PATHOLOGY.T Mean (SD) 1.93 (0.75)
  N
  T1 60
  T2 138
  T3 17
  T4 13
     
  Significant markers N = 0
Clinical variable #7: 'PATHOLOGY.N'

No gene related to 'PATHOLOGY.N'.

Table S10.  Basic characteristics of clinical feature: 'PATHOLOGY.N'

PATHOLOGY.N Mean (SD) 0.61 (0.81)
  N
  N0 133
  N1 46
  N2 43
  N3 1
     
  Significant markers N = 0
Clinical variable #8: 'PATHOLOGICSPREAD(M)'

2 genes related to 'PATHOLOGICSPREAD(M)'.

Table S11.  Basic characteristics of clinical feature: 'PATHOLOGICSPREAD(M)'

PATHOLOGICSPREAD(M) Labels N
  M0 160
  M1 12
  MX 53
     
  Significant markers N = 2
List of 2 genes differentially expressed by 'PATHOLOGICSPREAD(M)'

Table S12.  Get Full Table List of 2 genes differentially expressed by 'PATHOLOGICSPREAD(M)'

ANOVA_P Q
EGFR|EGFR_PY1173-R-C 0.0001238 0.0215
TP53|P53-R-V 0.0001352 0.0234

Figure S4.  Get High-res Image As an example, this figure shows the association of EGFR|EGFR_PY1173-R-C to 'PATHOLOGICSPREAD(M)'. P value = 0.000124 with ANOVA analysis.

Clinical variable #9: 'TUMOR.STAGE'

No gene related to 'TUMOR.STAGE'.

Table S13.  Basic characteristics of clinical feature: 'TUMOR.STAGE'

TUMOR.STAGE Mean (SD) 1.82 (0.97)
  N
  Stage 1 116
  Stage 2 48
  Stage 3 49
  Stage 4 13
     
  Significant markers N = 0
Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

No gene related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S14.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 15
  YES 222
     
  Significant markers N = 0
Clinical variable #11: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 40.54 (27)
  Significant markers N = 0
Clinical variable #12: 'TOBACCOSMOKINGHISTORYINDICATOR'

10 genes related to 'TOBACCOSMOKINGHISTORYINDICATOR'.

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

TOBACCOSMOKINGHISTORYINDICATOR Labels N
  CURRENT REFORMED SMOKER FOR < OR = 15 YEARS 82
  CURRENT REFORMED SMOKER FOR > 15 YEARS 57
  CURRENT SMOKER 51
  LIFELONG NON-SMOKER 29
     
  Significant markers N = 10
List of 10 genes differentially expressed by 'TOBACCOSMOKINGHISTORYINDICATOR'

Table S17.  Get Full Table List of 10 genes differentially expressed by 'TOBACCOSMOKINGHISTORYINDICATOR'

ANOVA_P Q
EIF4EBP1|4E-BP1-R-V 4.332e-07 7.54e-05
EIF4EBP1|4E-BP1_PT70-R-C 4.397e-06 0.000761
EGFR|EGFR_PY1068-R-V 3.631e-05 0.00625
CHEK1|CHK1-R-C 7.379e-05 0.0126
AKT1 AKT2 AKT3|AKT_PS473-R-V 0.0001062 0.018
CASP7|CASPASE-7_CLEAVEDD198-R-C 0.0001138 0.0192
PDK1|PDK1_PS241-R-V 0.000124 0.0208
JUN|C-JUN_PS73-R-C 0.0001547 0.0258
MAPK9|JNK2-R-C 0.0001559 0.0259
BCL2L11|BIM-R-V 0.0001764 0.0291

Figure S5.  Get High-res Image As an example, this figure shows the association of EIF4EBP1|4E-BP1-R-V to 'TOBACCOSMOKINGHISTORYINDICATOR'. P value = 4.33e-07 with ANOVA analysis.

Clinical variable #13: 'YEAROFTOBACCOSMOKINGONSET'

No gene related to 'YEAROFTOBACCOSMOKINGONSET'.

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

YEAROFTOBACCOSMOKINGONSET Mean (SD) 1964.73 (14)
  Significant markers N = 0
Clinical variable #14: 'COMPLETENESS.OF.RESECTION'

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

Table S19.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 127
  R1 6
  R2 3
  RX 12
     
  Significant markers N = 0
Methods & Data
Input

  • Expresson data file = LUAD-TP.rppa.txt

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

  • Number of patients = 237

  • 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)
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