Correlation between RPPA expression and clinical features
Stomach Adenocarcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between RPPA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1NS0TCR
Overview
Introduction

This pipeline uses various statistical tests to identify RPPAs whose expression levels correlated to selected clinical features. The input file "STAD-TP.rppa.txt" is generated in the pipeline RPPA_AnnotateWithGene in the stddata run.

Summary

Testing the association between 195 genes and 12 clinical features across 357 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one genes.

  • 16 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • MYH9|MYOSIN-IIA_PS1943 ,  CLDN7|CLAUDIN-7 ,  SYK|SYK ,  C12ORF5|TIGAR ,  RPS6KA1|P90RSK ,  ...

  • 20 genes correlated to 'YEARS_TO_BIRTH'.

    • IGFBP2|IGFBP2 ,  KIT|C-KIT ,  PRKCD|PKC-DELTA_PS664 ,  CLDN7|CLAUDIN-7 ,  MAP2K1|MEK1 ,  ...

  • 30 genes correlated to 'PATHOLOGIC_STAGE'.

    • CTNNB1|ALPHA-CATENIN ,  BIRC2 |CIAP ,  NFKB1|NF-KB-P65_PS536 ,  MAP2K1|MEK1_PS217_S221 ,  PEA15|PEA15 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • RB1|RB_PS807_S811 ,  BIRC2 |CIAP ,  SRC|SRC_PY416 ,  CTNNB1|ALPHA-CATENIN ,  PEA15|PEA15 ,  ...

  • 5 genes correlated to 'PATHOLOGY_N_STAGE'.

    • MAP2K1|MEK1_PS217_S221 ,  EIF4EBP1|4E-BP1 ,  MS4A1|CD20 ,  ETS1|ETS-1 ,  EIF4E|EIF4E

  • 30 genes correlated to 'RADIATION_THERAPY'.

    • ACVRL1|ACVRL1 ,  COL6A1|COLLAGEN_VI ,  BRCA2|BRCA2 ,  PGR|PR ,  CDKN1A|P21 ,  ...

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • ACACA|ACC1 ,  PCNA|PCNA ,  FASN|FASN ,  RPS6|S6 ,  CTNNB1|ALPHA-CATENIN ,  ...

  • 30 genes correlated to 'RESIDUAL_TUMOR'.

    • ESR1|ER-ALPHA_PS118 ,  MET|C-MET_PY1235 ,  BID|BID ,  SMAD1|SMAD1 ,  FRAP1|MTOR_PS2448 ,  ...

  • 4 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

    • EIF4EBP1|4E-BP1 ,  EIF4E|EIF4E ,  CHEK1|CHK1_PS345 ,  ETS1|ETS-1

  • 30 genes correlated to 'RACE'.

    • PRDX1|PRDX1 ,  SMAD3|SMAD3 ,  CDH3|P-CADHERIN ,  FASN|FASN ,  COL6A1|COLLAGEN_VI ,  ...

  • No genes correlated to 'PATHOLOGY_M_STAGE', and 'GENDER'.

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=16   N=NA   N=NA
YEARS_TO_BIRTH Spearman correlation test N=20 older N=11 younger N=9
PATHOLOGIC_STAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=18 lower stage N=12
PATHOLOGY_N_STAGE Spearman correlation test N=5 higher stage N=2 lower stage N=3
PATHOLOGY_M_STAGE Wilcoxon test   N=0        
GENDER Wilcoxon test   N=0        
RADIATION_THERAPY Wilcoxon test N=30 yes N=30 no N=0
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
RESIDUAL_TUMOR Kruskal-Wallis test N=30        
NUMBER_OF_LYMPH_NODES Spearman correlation test N=4 higher number_of_lymph_nodes N=2 lower number_of_lymph_nodes N=2
RACE Kruskal-Wallis test N=30        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

16 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) 0.1-122.3 (median=14.4)
  censored N = 212
  death N = 144
     
  Significant markers N = 16
  associated with shorter survival NA
  associated with longer survival NA
List of top 10 genes differentially expressed by 'DAYS_TO_DEATH_OR_LAST_FUP'

Table S2.  Get Full Table List of top 10 genes significantly associated with 'Time to Death' by Cox regression test. For the survival curves, it compared quantile intervals at c(0, 0.25, 0.50, 0.75, 1) and did not try survival analysis if there is only one interval.

logrank_P Q C_index
MYH9|MYOSIN-IIA_PS1943 0.00026 0.051 0.442
CLDN7|CLAUDIN-7 0.000861 0.084 0.419
SYK|SYK 0.00178 0.1 0.437
C12ORF5|TIGAR 0.00204 0.1 0.406
RPS6KA1|P90RSK 0.00267 0.1 0.43
RICTOR|RICTOR 0.00518 0.16 0.573
MYH11|MYH11 0.00619 0.16 0.565
CDKN1A|P21 0.00657 0.16 0.541
ACVRL1|ACVRL1 0.0097 0.21 0.552
CAV1|CAVEOLIN-1 0.0117 0.23 0.563
Clinical variable #2: 'YEARS_TO_BIRTH'

20 genes related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 65.66 (11)
  Significant markers N = 20
  pos. correlated 11
  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
IGFBP2|IGFBP2 -0.1666 0.001785 0.123
KIT|C-KIT -0.1659 0.001872 0.123
PRKCD|PKC-DELTA_PS664 -0.1586 0.002976 0.123
CLDN7|CLAUDIN-7 0.1579 0.003106 0.123
MAP2K1|MEK1 0.1576 0.003146 0.123
TFRC|TFRC 0.1531 0.004157 0.135
PRKCA |PKC-ALPHA -0.1459 0.006317 0.146
SMAD1|SMAD1 0.1437 0.007176 0.146
SRC|SRC_PY416 0.1426 0.007639 0.146
PEA15|PEA15 -0.1423 0.007748 0.146
Clinical variable #3: 'PATHOLOGIC_STAGE'

30 genes related to 'PATHOLOGIC_STAGE'.

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

PATHOLOGIC_STAGE Labels N
  STAGE I 2
  STAGE IA 11
  STAGE IB 32
  STAGE II 29
  STAGE IIA 32
  STAGE IIB 44
  STAGE III 2
  STAGE IIIA 67
  STAGE IIIB 51
  STAGE IIIC 32
  STAGE IV 33
     
  Significant markers N = 30
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
CTNNB1|ALPHA-CATENIN 9.356e-05 0.0116
BIRC2 |CIAP 0.0001186 0.0116
NFKB1|NF-KB-P65_PS536 0.0006969 0.0453
MAP2K1|MEK1_PS217_S221 0.001214 0.0479
PEA15|PEA15 0.001227 0.0479
TGM2|TRANSGLUTAMINASE 0.002763 0.0783
EEF2K|EEF2K 0.002812 0.0783
LCK|LCK 0.004091 0.0827
TSC2|TUBERIN_PT1462 0.004203 0.0827
SRC|SRC_PY527 0.004242 0.0827
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) 2.99 (0.82)
  N
  T1 14
  T2 76
  T3 156
  T4 101
     
  Significant markers N = 30
  pos. correlated 18
  neg. correlated 12
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
RB1|RB_PS807_S811 -0.251 2.186e-06 0.000304
BIRC2 |CIAP -0.2473 3.122e-06 0.000304
SRC|SRC_PY416 -0.2318 1.291e-05 0.000719
CTNNB1|ALPHA-CATENIN -0.2303 1.475e-05 0.000719
PEA15|PEA15 0.222 3.017e-05 0.00118
SRC|SRC_PY527 -0.198 0.000206 0.0067
EIF4E|EIF4E -0.1952 0.0002543 0.00708
RICTOR|RICTOR 0.1875 0.0004445 0.0108
ACVRL1|ACVRL1 0.1743 0.001116 0.0242
BRCA2|BRCA2 0.1623 0.002425 0.0432
Clinical variable #5: 'PATHOLOGY_N_STAGE'

5 genes related to 'PATHOLOGY_N_STAGE'.

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

PATHOLOGY_N_STAGE Mean (SD) 1.29 (1.1)
  N
  N0 109
  N1 96
  N2 65
  N3 71
     
  Significant markers N = 5
  pos. correlated 2
  neg. correlated 3
List of 5 genes differentially expressed by 'PATHOLOGY_N_STAGE'

Table S10.  Get Full Table List of 5 genes significantly correlated to 'PATHOLOGY_N_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
MAP2K1|MEK1_PS217_S221 -0.164 0.002381 0.171
EIF4EBP1|4E-BP1 -0.1629 0.002547 0.171
MS4A1|CD20 0.1624 0.002634 0.171
ETS1|ETS-1 0.1527 0.004704 0.204
EIF4E|EIF4E -0.1509 0.005243 0.204
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 322
  class1 21
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

No gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 121
  MALE 236
     
  Significant markers N = 0
Clinical variable #8: 'RADIATION_THERAPY'

30 genes related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 265
  YES 57
     
  Significant markers N = 30
  Higher in YES 30
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATION_THERAPY'

Table S14.  Get Full Table List of top 10 genes differentially expressed by 'RADIATION_THERAPY'

W(pos if higher in 'YES') wilcoxontestP Q AUC
ACVRL1|ACVRL1 4800 1.589e-05 0.0031 0.6822
COL6A1|COLLAGEN_VI 5174 0.0001919 0.0185 0.6575
BRCA2|BRCA2 5280 0.0003664 0.0185 0.6504
PGR|PR 5318 0.000459 0.0185 0.6479
CDKN1A|P21 5354 0.0005666 0.0185 0.6455
C12ORF5|TIGAR 9750 0.0005699 0.0185 0.6455
BCL2|BCL-2 5591 0.002102 0.0563 0.6299
ACACA|ACC1 9489 0.002396 0.0563 0.6282
PEA15|PEA15 5633.5 0.002623 0.0563 0.627
YWHAE|14-3-3_EPSILON 5666 0.003098 0.0563 0.6249
Clinical variable #9: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  STOMACH ADENOCARCINOMA, SIGNET RING TYPE 10
  STOMACH, ADENOCARCINOMA, DIFFUSE TYPE 52
  STOMACH, ADENOCARCINOMA, NOT OTHERWISE SPECIFIED (NOS) 149
  STOMACH, INTESTINAL ADENOCARCINOMA, MUCINOUS TYPE 19
  STOMACH, INTESTINAL ADENOCARCINOMA, NOT OTHERWISE SPECIFIED (NOS) 69
  STOMACH, INTESTINAL ADENOCARCINOMA, PAPILLARY TYPE 5
  STOMACH, INTESTINAL ADENOCARCINOMA, TUBULAR TYPE 50
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S16.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

kruskal_wallis_P Q
ACACA|ACC1 8.344e-05 0.00643
PCNA|PCNA 8.927e-05 0.00643
FASN|FASN 9.892e-05 0.00643
RPS6|S6 0.0003129 0.0123
CTNNB1|ALPHA-CATENIN 0.0003152 0.0123
MAPK8|JNK_PT183_PY185 0.00145 0.042
TGM2|TRANSGLUTAMINASE 0.001518 0.042
BECN1|BECLIN 0.001782 0.042
BCL2L1|BCL-XL 0.002159 0.042
BCL2|BCL-2 0.002239 0.042
Clinical variable #10: 'RESIDUAL_TUMOR'

30 genes related to 'RESIDUAL_TUMOR'.

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

RESIDUAL_TUMOR Labels N
  R0 282
  R1 15
  R2 14
  RX 25
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RESIDUAL_TUMOR'

Table S18.  Get Full Table List of top 10 genes differentially expressed by 'RESIDUAL_TUMOR'

kruskal_wallis_P Q
ESR1|ER-ALPHA_PS118 2.531e-06 0.000493
MET|C-MET_PY1235 1.154e-05 0.00112
BID|BID 0.0004903 0.0319
SMAD1|SMAD1 0.001213 0.0592
FRAP1|MTOR_PS2448 0.006381 0.208
YBX1|YB-1 0.007352 0.208
PKC|PKC-PAN_BETAII_PS660 0.007466 0.208
ERBB3|HER3_PY1289 0.009917 0.213
GSK3A GSK3B|GSK3-ALPHA-BETA 0.01155 0.213
YBX1|YB-1_PS102 0.01218 0.213
Clinical variable #11: 'NUMBER_OF_LYMPH_NODES'

4 genes related to 'NUMBER_OF_LYMPH_NODES'.

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

NUMBER_OF_LYMPH_NODES Mean (SD) 5.5 (7.9)
  Significant markers N = 4
  pos. correlated 2
  neg. correlated 2
List of 4 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

Table S20.  Get Full Table List of 4 genes significantly correlated to 'NUMBER_OF_LYMPH_NODES' by Spearman correlation test

SpearmanCorr corrP Q
EIF4EBP1|4E-BP1 -0.1951 0.0005164 0.101
EIF4E|EIF4E -0.1825 0.001181 0.115
CHEK1|CHK1_PS345 0.1626 0.003912 0.254
ETS1|ETS-1 0.157 0.005369 0.262
Clinical variable #12: 'RACE'

30 genes related to 'RACE'.

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

RACE Labels N
  ASIAN 66
  BLACK OR AFRICAN AMERICAN 5
  NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 1
  WHITE 232
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S22.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
PRDX1|PRDX1 0.0001365 0.0266
SMAD3|SMAD3 0.0009572 0.0933
CDH3|P-CADHERIN 0.002824 0.184
FASN|FASN 0.004414 0.215
COL6A1|COLLAGEN_VI 0.005741 0.224
CHEK2|CHK2 0.007797 0.253
ERBB2|HER2_PY1248 0.00985 0.274
RPS6KB1|P70S6K_PT389 0.01217 0.274
BECN1|BECLIN 0.01487 0.274
CCND1|CYCLIN_D1 0.0176 0.274
Methods & Data
Input
  • Expresson data file = STAD-TP.rppa.txt

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

  • Number of patients = 357

  • Number of genes = 195

  • Number of clinical features = 12

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, logrank test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values comparing quantile intervals using the 'coxph' function in R. Kaplan-Meier survival curves were plotted using quantile intervals at c(0, 0.25, 0.50, 0.75, 1). If there is only one interval group, it will not try survival analysis.

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)