Correlation between RPPA expression and clinical features
Lung Squamous Cell Carcinoma (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
doi:10.7908/C1B857CN
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Correlation between RPPA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1B857CN
Overview
Introduction

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

Summary

Testing the association between 223 genes and 15 clinical features across 327 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 9 clinical features related to at least one genes.

  • 4 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • CHEK2|CHK2 ,  PXN|PAXILLIN ,  BRCA2|BRCA2 ,  COL6A1|COLLAGEN_VI

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • PCNA|PCNA ,  ERBB2|HER2_PY1248 ,  TSC2|TUBERIN_PT1462 ,  SRC|SRC_PY416 ,  AKT1S1|PRAS40_PT246 ,  ...

  • 26 genes correlated to 'PATHOLOGIC_STAGE'.

    • MTOR|MTOR_PS2448 ,  MAPK1 MAPK3|MAPK_PT202_Y204 ,  RPS6|S6_PS235_S236 ,  CCND1|CYCLIN_D1 ,  JUN|C-JUN_PS73 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • MTOR|MTOR_PS2448 ,  ITGA2|CD49B ,  MAPK1 MAPK3|MAPK_PT202_Y204 ,  BID|BID ,  TSC2|TUBERIN_PT1462 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • MAPK1 MAPK3|MAPK_PT202_Y204 ,  RPS6|S6_PS235_S236 ,  STAT3|STAT3_PY705 ,  MTOR|MTOR_PS2448 ,  PDCD4|PDCD4 ,  ...

  • 30 genes correlated to 'GENDER'.

    • PDCD1|PDCD1 ,  GAB2|GAB2 ,  PRKCB|PKC-PAN_BETAII_PS660 ,  GAPDH|GAPDH ,  ACACA|ACC1 ,  ...

  • 26 genes correlated to 'HISTOLOGICAL_TYPE'.

    • MSH2|MSH2 ,  SRSF1|SF2 ,  RAD51|RAD51 ,  ARID1A|ARID1A ,  PARP1|PARP1 ,  ...

  • 2 genes correlated to 'YEAR_OF_TOBACCO_SMOKING_ONSET'.

    • SRC|SRC_PY416 ,  ERRFI1|MIG-6

  • 1 gene correlated to 'RESIDUAL_TUMOR'.

    • GSK3A GSK3B|GSK3-ALPHA-BETA

  • No genes correlated to 'PATHOLOGY_M_STAGE', 'RADIATION_THERAPY', 'KARNOFSKY_PERFORMANCE_SCORE', 'NUMBER_PACK_YEARS_SMOKED', 'RACE', and 'ETHNICITY'.

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 P value < 0.05 and Q value < 0.3.

Clinical feature Statistical test Significant genes Associated with                 Associated with
DAYS_TO_DEATH_OR_LAST_FUP Cox regression test N=4 shorter survival N=3 longer survival N=1
YEARS_TO_BIRTH Spearman correlation test N=30 older N=21 younger N=9
PATHOLOGIC_STAGE Kruskal-Wallis test N=26        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=15 lower stage N=15
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=9 lower stage N=21
PATHOLOGY_M_STAGE Wilcoxon test   N=0        
GENDER Wilcoxon test N=30 male N=30 female N=0
RADIATION_THERAPY Wilcoxon test   N=0        
KARNOFSKY_PERFORMANCE_SCORE Spearman correlation test   N=0        
HISTOLOGICAL_TYPE Kruskal-Wallis test N=26        
NUMBER_PACK_YEARS_SMOKED Spearman correlation test   N=0        
YEAR_OF_TOBACCO_SMOKING_ONSET Spearman correlation test N=2 higher year_of_tobacco_smoking_onset N=1 lower year_of_tobacco_smoking_onset N=1
RESIDUAL_TUMOR Kruskal-Wallis test N=1        
RACE Kruskal-Wallis test   N=0        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

4 genes related to 'DAYS_TO_DEATH_OR_LAST_FUP'.

Table S1.  Basic characteristics of clinical feature: 'DAYS_TO_DEATH_OR_LAST_FUP'

DAYS_TO_DEATH_OR_LAST_FUP Duration (Months) 0-173.8 (median=22.4)
  censored N = 190
  death N = 136
     
  Significant markers N = 4
  associated with shorter survival 3
  associated with longer survival 1
List of 4 genes differentially expressed by 'DAYS_TO_DEATH_OR_LAST_FUP'

Table S2.  Get Full Table List of 4 genes significantly associated with 'Time to Death' by Cox regression test

HazardRatio Wald_P Q C_index
CHEK2|CHK2 0.43 0.0001224 0.027 0.396
PXN|PAXILLIN 1.61 0.001125 0.11 0.606
BRCA2|BRCA2 3.1 0.001482 0.11 0.607
COL6A1|COLLAGEN_VI 1.7 0.004619 0.26 0.541
Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 67.09 (8.9)
  Significant markers N = 30
  pos. correlated 21
  neg. correlated 9
List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

Table S4.  Get Full Table List of top 10 genes significantly correlated to 'YEARS_TO_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
PCNA|PCNA -0.2376 1.797e-05 0.00401
ERBB2|HER2_PY1248 0.214 0.0001171 0.0112
TSC2|TUBERIN_PT1462 0.2106 0.0001513 0.0112
SRC|SRC_PY416 0.2038 0.000249 0.0139
AKT1S1|PRAS40_PT246 0.1925 0.0005455 0.0197
CCNB1|CYCLIN_B1 -0.1916 0.0005815 0.0197
RET|RET_PY905 0.2473 0.0006429 0.0197
AKT1 AKT2 AKT3|AKT_PS473 0.1886 0.0007077 0.0197
FOXO3|FOXO3A_PS318_S321 0.1865 0.0008185 0.0203
JUN|C-JUN_PS73 0.1826 0.001054 0.0235
Clinical variable #3: 'PATHOLOGIC_STAGE'

26 genes related to 'PATHOLOGIC_STAGE'.

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGIC_STAGE'

PATHOLOGIC_STAGE Labels N
  STAGE I 2
  STAGE IA 52
  STAGE IB 100
  STAGE II 3
  STAGE IIA 46
  STAGE IIB 61
  STAGE III 2
  STAGE IIIA 42
  STAGE IIIB 14
  STAGE IV 3
     
  Significant markers N = 26
List of top 10 genes differentially expressed by 'PATHOLOGIC_STAGE'

Table S6.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGIC_STAGE'

kruskal_wallis_P Q
MTOR|MTOR_PS2448 8.828e-06 0.00103
MAPK1 MAPK3|MAPK_PT202_Y204 9.249e-06 0.00103
RPS6|S6_PS235_S236 0.0002743 0.018
CCND1|CYCLIN_D1 0.0003232 0.018
JUN|C-JUN_PS73 0.001404 0.0588
SRC|SRC_PY527 0.001582 0.0588
BAD|BAD_PS112 0.00281 0.0895
PDCD4|PDCD4 0.004682 0.131
SHC1|SHC_PY317 0.006 0.142
KIT|C-KIT 0.006485 0.142
Clinical variable #4: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'

PATHOLOGY_T_STAGE Mean (SD) 2.03 (0.75)
  N
  T1 70
  T2 193
  T3 48
  T4 16
     
  Significant markers N = 30
  pos. correlated 15
  neg. correlated 15
List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S8.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
MTOR|MTOR_PS2448 -0.2636 1.338e-06 0.000288
ITGA2|CD49B 0.2566 2.586e-06 0.000288
MAPK1 MAPK3|MAPK_PT202_Y204 -0.2233 4.612e-05 0.00343
BID|BID 0.2069 0.0001649 0.00919
TSC2|TUBERIN_PT1462 -0.1962 0.0003585 0.0134
PARP1|PARP-AB-3 0.2529 0.0003614 0.0134
SERPINE1|PAI-1 0.1906 0.000529 0.0169
SYP|SYNAPTOPHYSIN -0.2395 0.0007475 0.0208
KIT|C-KIT -0.1822 0.000936 0.0232
FN1|FIBRONECTIN 0.1738 0.001607 0.0358
Clinical variable #5: 'PATHOLOGY_N_STAGE'

30 genes related to 'PATHOLOGY_N_STAGE'.

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY_N_STAGE'

PATHOLOGY_N_STAGE Mean (SD) 0.47 (0.7)
  N
  N0 204
  N1 89
  N2 26
  N3 4
     
  Significant markers N = 30
  pos. correlated 9
  neg. correlated 21
List of top 10 genes differentially expressed by 'PATHOLOGY_N_STAGE'

Table S10.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_N_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
MAPK1 MAPK3|MAPK_PT202_Y204 -0.2851 1.865e-07 4.16e-05
RPS6|S6_PS235_S236 -0.2356 1.88e-05 0.0021
STAT3|STAT3_PY705 -0.2227 5.378e-05 0.00377
MTOR|MTOR_PS2448 -0.2198 6.764e-05 0.00377
PDCD4|PDCD4 -0.208 0.000166 0.0074
MAP2K1|MEK1_PS217_S221 -0.2046 0.0002132 0.00792
MAPK14|P38_PT180_Y182 -0.1755 0.001545 0.0479
PCNA|PCNA 0.1732 0.001787 0.0479
PARP1|PARP1 0.2695 0.001932 0.0479
JUN|C-JUN_PS73 -0.1662 0.002729 0.0609
Clinical variable #6: 'PATHOLOGY_M_STAGE'

No gene related to 'PATHOLOGY_M_STAGE'.

Table S11.  Basic characteristics of clinical feature: 'PATHOLOGY_M_STAGE'

PATHOLOGY_M_STAGE Labels N
  class0 278
  class1 3
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

30 genes related to 'GENDER'.

Table S12.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 80
  MALE 247
     
  Significant markers N = 30
  Higher in MALE 30
  Higher in FEMALE 0
List of top 10 genes differentially expressed by 'GENDER'

Table S13.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'. 0 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
PDCD1|PDCD1 4827 0.0002569 0.0573 0.6747
GAB2|GAB2 7394 0.0007196 0.0732 0.6258
PRKCB|PKC-PAN_BETAII_PS660 7458 0.0009845 0.0732 0.6226
GAPDH|GAPDH 12221 0.001449 0.0758 0.6185
ACACA|ACC1 12187 0.001699 0.0758 0.6168
LCK|LCK 7658 0.002505 0.0865 0.6124
MTOR|MTOR_PS2448 7676 0.002715 0.0865 0.6115
KIT|C-KIT 7809 0.004843 0.135 0.6048
SYK|SYK 7876 0.006408 0.156 0.6014
SQSTM1|P62-LCK-LIGAND 11846 0.007485 0.156 0.5995
Clinical variable #8: 'RADIATION_THERAPY'

No gene related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 253
  YES 34
     
  Significant markers N = 0
Clinical variable #9: 'KARNOFSKY_PERFORMANCE_SCORE'

No gene related to 'KARNOFSKY_PERFORMANCE_SCORE'.

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

KARNOFSKY_PERFORMANCE_SCORE Mean (SD) 64.44 (40)
  Significant markers N = 0
Clinical variable #10: 'HISTOLOGICAL_TYPE'

26 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  LUNG BASALOID SQUAMOUS CELL CARCINOMA 8
  LUNG PAPILLARY SQUAMOUS CELL CARICNOMA 4
  LUNG SQUAMOUS CELL CARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 315
     
  Significant markers N = 26
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

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

kruskal_wallis_P Q
MSH2|MSH2 0.002789 0.248
SRSF1|SF2 0.004164 0.248
RAD51|RAD51 0.004968 0.248
ARID1A|ARID1A 0.005078 0.248
PARP1|PARP1 0.008354 0.248
CHEK2|CHK2 0.009231 0.248
FN1|FIBRONECTIN 0.009337 0.248
KDR|VEGFR2 0.01152 0.248
BCL2L11|BIM 0.0122 0.248
TIGAR|TIGAR 0.01372 0.248
Clinical variable #11: 'NUMBER_PACK_YEARS_SMOKED'

No gene related to 'NUMBER_PACK_YEARS_SMOKED'.

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

NUMBER_PACK_YEARS_SMOKED Mean (SD) 50.5 (30)
  Significant markers N = 0
Clinical variable #12: 'YEAR_OF_TOBACCO_SMOKING_ONSET'

2 genes related to 'YEAR_OF_TOBACCO_SMOKING_ONSET'.

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

YEAR_OF_TOBACCO_SMOKING_ONSET Mean (SD) 1960.88 (12)
  Significant markers N = 2
  pos. correlated 1
  neg. correlated 1
List of 2 genes differentially expressed by 'YEAR_OF_TOBACCO_SMOKING_ONSET'

Table S20.  Get Full Table List of 2 genes significantly correlated to 'YEAR_OF_TOBACCO_SMOKING_ONSET' by Spearman correlation test

SpearmanCorr corrP Q
SRC|SRC_PY416 -0.2299 0.0007867 0.175
ERRFI1|MIG-6 0.2084 0.002407 0.268
Clinical variable #13: 'RESIDUAL_TUMOR'

One gene related to 'RESIDUAL_TUMOR'.

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

RESIDUAL_TUMOR Labels N
  R0 256
  R1 7
  R2 4
  RX 12
     
  Significant markers N = 1
List of one gene differentially expressed by 'RESIDUAL_TUMOR'

Table S22.  Get Full Table List of one gene differentially expressed by 'RESIDUAL_TUMOR'

kruskal_wallis_P Q
GSK3A GSK3B|GSK3-ALPHA-BETA 0.001241 0.277
Clinical variable #14: 'RACE'

No gene related to 'RACE'.

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

RACE Labels N
  ASIAN 6
  BLACK OR AFRICAN AMERICAN 19
  WHITE 241
     
  Significant markers N = 0
Clinical variable #15: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S24.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 4
  NOT HISPANIC OR LATINO 212
     
  Significant markers N = 0
Methods & Data
Input

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

  • Clinical data file = LUSC-TP.merged_data.txt

  • Number of patients = 327

  • Number of genes = 223

  • Number of clinical features = 15

Selected clinical features

  • Further details on clinical features selected for this analysis, please find a documentation on selected CDEs (Clinical Data Elements). The first column of the file is a formula to convert values and the second column is a clinical parameter name.

  • Survival time data

    • Survival time data is a combined value of days_to_death and days_to_last_followup. For each patient, it creates a combined value 'days_to_death_or_last_fup' using conversion process below.

      • if 'vital_status'==1(dead), 'days_to_last_followup' is always NA. Thus, uses 'days_to_death' value for 'days_to_death_or_fup'

      • if 'vital_status'==0(alive),

        • if 'days_to_death'==NA & 'days_to_last_followup'!=NA, uses 'days_to_last_followup' value for 'days_to_death_or_fup'

        • if 'days_to_death'!=NA, excludes this case in survival analysis and report the case.

      • if 'vital_status'==NA,excludes this case in survival analysis and report the case.

    • cf. In certain diesase types such as SKCM, days_to_death parameter is replaced with time_from_specimen_dx or time_from_specimen_procurement_to_death .

  • This analysis excluded clinical variables that has only NA values.

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

Wilcoxon rank sum test (Mann-Whitney U test)

For two groups (mutant or wild-type) of continuous type of clinical data, wilcoxon rank sum test (Mann and Whitney, 1947) was applied to compare their mean difference using 'wilcox.test(continuous.clinical ~ as.factor(group), exact=FALSE)' function in R. This test is equivalent to the Mann-Whitney test.

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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

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] Mann and Whitney, On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other, Annals of Mathematical Statistics 18 (1), 50-60 (1947)
[4] 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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