Correlation between RPPA expression and clinical features
Stomach Adenocarcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1MS3RWG
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/C1MS3RWG
Overview
Introduction

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

Summary

Testing the association between 189 genes and 12 clinical features across 264 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one genes.

  • 13 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • ESR1|ER-ALPHA_PS118-R-V ,  CDC2|CDK1-R-V ,  DVL3|DVL3-R-V ,  C12ORF5|TIGAR-R-V ,  EGFR|EGFR-R-V ,  ...

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • CLDN7|CLAUDIN-7-R-V ,  SMAD1|SMAD1-R-V ,  PEA15|PEA15-R-V ,  KIT|C-KIT-R-V ,  BIRC2 |CIAP-R-V ,  ...

  • 30 genes correlated to 'NEOPLASM_DISEASESTAGE'.

    • PEA15|PEA15-R-V ,  CTNNA1|ALPHA-CATENIN-M-V ,  LCK|LCK-R-V ,  BIRC2 |CIAP-R-V ,  NDRG1|NDRG1_PT346-R-V ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • RB1|RB_PS807_S811-R-V ,  BIRC2 |CIAP-R-V ,  PEA15|PEA15-R-V ,  CTNNA1|ALPHA-CATENIN-M-V ,  RICTOR|RICTOR-R-C ,  ...

  • 2 genes correlated to 'PATHOLOGY_N_STAGE'.

    • MS4A1|CD20-R-C ,  EIF4EBP1|4E-BP1-R-V

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • MAPK8|JNK_PT183_PY185-R-V ,  CTNNA1|ALPHA-CATENIN-M-V ,  RPS6|S6-R-E ,  FASN|FASN-R-V ,  ACACA|ACC1-R-E ,  ...

  • 30 genes correlated to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

    • BRCA2|BRCA2-R-C ,  BID|BID-R-C ,  ACACA ACACB|ACC_PS79-R-V ,  ACVRL1|ACVRL1-R-C ,  AR|AR-R-V ,  ...

  • 30 genes correlated to 'COMPLETENESS_OF_RESECTION'.

    • ESR1|ER-ALPHA_PS118-R-V ,  MET|C-MET_PY1235-R-V ,  BID|BID-R-C ,  PKC|PKC-PAN_BETAII_PS660-R-V ,  SHC1|SHC_PY317-R-E ,  ...

  • 2 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

    • EIF4EBP1|4E-BP1-R-V ,  EIF4E|EIF4E-R-V

  • 30 genes correlated to 'RACE'.

    • SMAD3|SMAD3-R-V ,  PRDX1|PRDX1-R-V ,  COL6A1|COLLAGEN_VI-R-V ,  MS4A1|CD20-R-C ,  RPTOR|RAPTOR-R-V ,  ...

  • 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=13 shorter survival N=7 longer survival N=6
YEARS_TO_BIRTH Spearman correlation test N=30 older N=16 younger N=14
NEOPLASM_DISEASESTAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=19 lower stage N=11
PATHOLOGY_N_STAGE Spearman correlation test N=2 higher stage N=1 lower stage N=1
PATHOLOGY_M_STAGE Wilcoxon test   N=0        
GENDER Wilcoxon test   N=0        
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
RADIATIONS_RADIATION_REGIMENINDICATION Wilcoxon test N=30 yes N=30 no N=0
COMPLETENESS_OF_RESECTION Kruskal-Wallis test N=30        
NUMBER_OF_LYMPH_NODES Spearman correlation test N=2 higher number_of_lymph_nodes N=0 lower number_of_lymph_nodes N=2
RACE Kruskal-Wallis test N=30        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

13 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) 0.1-105.1 (median=12.8)
  censored N = 185
  death N = 78
     
  Significant markers N = 13
  associated with shorter survival 7
  associated with longer survival 6
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

HazardRatio Wald_P Q C_index
ESR1|ER-ALPHA_PS118-R-V 13 0.0009818 0.074 0.641
CDC2|CDK1-R-V 0.48 0.0009828 0.074 0.388
DVL3|DVL3-R-V 4.3 0.001176 0.074 0.605
C12ORF5|TIGAR-R-V 0.49 0.001932 0.082 0.4
EGFR|EGFR-R-V 1.86 0.002176 0.082 0.596
MS4A1|CD20-R-C 4.2 0.002933 0.092 0.582
CLDN7|CLAUDIN-7-R-V 0.74 0.004267 0.12 0.439
RPS6KA1|P90RSK-R-C 0.45 0.00679 0.16 0.421
NDRG1|NDRG1_PT346-R-V 0.6 0.01106 0.23 0.398
PXN|PAXILLIN-R-C 1.63 0.0144 0.26 0.572
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) 65.85 (11)
  Significant markers N = 30
  pos. correlated 16
  neg. correlated 14
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
CLDN7|CLAUDIN-7-R-V 0.2285 0.0002205 0.0309
SMAD1|SMAD1-R-V 0.2211 0.0003542 0.0309
PEA15|PEA15-R-V -0.2159 0.000491 0.0309
KIT|C-KIT-R-V -0.1969 0.001514 0.0586
BIRC2 |CIAP-R-V 0.1965 0.001551 0.0586
PRKCD|PKC-DELTA_PS664-R-V -0.1927 0.001911 0.0602
TFRC|TFRC-R-V 0.1884 0.002422 0.0654
RPS6|S6_PS235_S236-R-V 0.1787 0.004063 0.0881
ASNS|ASNS-R-V 0.178 0.004194 0.0881
ACVRL1|ACVRL1-R-C -0.1742 0.005104 0.0965
Clinical variable #3: 'NEOPLASM_DISEASESTAGE'

30 genes related to 'NEOPLASM_DISEASESTAGE'.

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

NEOPLASM_DISEASESTAGE Labels N
  STAGE I 2
  STAGE IA 6
  STAGE IB 25
  STAGE II 28
  STAGE IIA 25
  STAGE IIB 36
  STAGE III 3
  STAGE IIIA 42
  STAGE IIIB 34
  STAGE IIIC 24
  STAGE IV 23
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'NEOPLASM_DISEASESTAGE'

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

kruskal_wallis_P Q
PEA15|PEA15-R-V 3.839e-05 0.00502
CTNNA1|ALPHA-CATENIN-M-V 5.316e-05 0.00502
LCK|LCK-R-V 0.0003875 0.0244
BIRC2 |CIAP-R-V 0.0007653 0.0349
NDRG1|NDRG1_PT346-R-V 0.0009222 0.0349
CCND1|CYCLIN_D1-R-V 0.001558 0.0432
TGM2|TRANSGLUTAMINASE-M-V 0.001677 0.0432
MS4A1|CD20-R-C 0.001829 0.0432
STK11|LKB1-M-E 0.0022 0.0462
RB1|RB_PS807_S811-R-V 0.002636 0.0498
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) 2.96 (0.83)
  N
  T1 8
  T2 67
  T3 105
  T4 74
     
  Significant markers N = 30
  pos. correlated 19
  neg. correlated 11
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-R-V -0.2882 3.01e-06 0.000302
BIRC2 |CIAP-R-V -0.2875 3.194e-06 0.000302
PEA15|PEA15-R-V 0.2524 4.718e-05 0.00194
CTNNA1|ALPHA-CATENIN-M-V -0.2499 5.655e-05 0.00194
RICTOR|RICTOR-R-C 0.2484 6.256e-05 0.00194
ACVRL1|ACVRL1-R-C 0.2477 6.572e-05 0.00194
MYH11|MYH11-R-V 0.245 7.944e-05 0.00194
BRCA2|BRCA2-R-C 0.2446 8.207e-05 0.00194
EIF4E|EIF4E-R-V -0.2327 0.0001826 0.00383
BCL2|BCL-2-M-V 0.2304 0.0002121 0.00401
Clinical variable #5: 'PATHOLOGY_N_STAGE'

2 genes related to 'PATHOLOGY_N_STAGE'.

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

PATHOLOGY_N_STAGE Mean (SD) 1.22 (1.1)
  N
  N0 87
  N1 73
  N2 42
  N3 50
     
  Significant markers N = 2
  pos. correlated 1
  neg. correlated 1
List of 2 genes differentially expressed by 'PATHOLOGY_N_STAGE'

Table S10.  Get Full Table List of 2 genes significantly correlated to 'PATHOLOGY_N_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
MS4A1|CD20-R-C 0.1927 0.002124 0.227
EIF4EBP1|4E-BP1-R-V -0.1904 0.002404 0.227
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 237
  class1 16
     
  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 99
  MALE 165
     
  Significant markers N = 0
Clinical variable #8: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  STOMACH ADENOCARCINOMA DIFFUSE TYPE 42
  STOMACH ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 135
  STOMACH INTESTINAL ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 37
  STOMACH INTESTINAL ADENOCARCINOMA TUBULAR TYPE 26
  STOMACH INTESTINAL ADENOCARCINOMA  MUCINOUS TYPE 16
  STOMACH INTESTINAL ADENOCARCINOMA  PAPILLARY TYPE 4
  STOMACH ADENOCARCINOMA SIGNET RING TYPE 2
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

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

kruskal_wallis_P Q
MAPK8|JNK_PT183_PY185-R-V 0.0003916 0.0324
CTNNA1|ALPHA-CATENIN-M-V 0.0006371 0.0324
RPS6|S6-R-E 0.0006546 0.0324
FASN|FASN-R-V 0.0006858 0.0324
ACACA|ACC1-R-E 0.001688 0.0434
EIF4EBP1|4E-BP1-R-V 0.001827 0.0434
BCL2|BCL-2-M-V 0.001844 0.0434
KIT|C-KIT-R-V 0.002026 0.0434
PCNA|PCNA-M-C 0.002205 0.0434
SHC1|SHC_PY317-R-E 0.002294 0.0434
Clinical variable #9: 'RADIATIONS_RADIATION_REGIMENINDICATION'

30 genes related to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

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

RADIATIONS_RADIATION_REGIMENINDICATION Labels N
  NO 6
  YES 258
     
  Significant markers N = 30
  Higher in YES 30
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATIONS_RADIATION_REGIMENINDICATION'

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

W(pos if higher in 'YES') wilcoxontestP Q AUC
BRCA2|BRCA2-R-C 1350 0.001854 0.0849 0.8721
BID|BID-R-C 1343 0.002107 0.0849 0.8676
ACACA ACACB|ACC_PS79-R-V 218 0.002661 0.0849 0.8592
ACVRL1|ACVRL1-R-C 1327 0.002806 0.0849 0.8572
AR|AR-R-V 1326 0.002856 0.0849 0.8566
PTEN|PTEN-R-V 226 0.003065 0.0849 0.854
ESR1|ER-ALPHA-R-V 1313 0.003585 0.0849 0.8482
FN1|FIBRONECTIN-R-V 1309 0.003842 0.0849 0.8456
PEA15|PEA15-R-V 1306 0.004045 0.0849 0.8437
C12ORF5|TIGAR-R-V 259 0.005391 0.0938 0.8327
Clinical variable #10: 'COMPLETENESS_OF_RESECTION'

30 genes related to 'COMPLETENESS_OF_RESECTION'.

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

COMPLETENESS_OF_RESECTION Labels N
  R0 206
  R1 9
  R2 8
  RX 25
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'COMPLETENESS_OF_RESECTION'

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

kruskal_wallis_P Q
ESR1|ER-ALPHA_PS118-R-V 5.033e-06 0.000951
MET|C-MET_PY1235-R-V 1.23e-05 0.00116
BID|BID-R-C 0.0001554 0.00979
PKC|PKC-PAN_BETAII_PS660-R-V 0.001126 0.0532
SHC1|SHC_PY317-R-E 0.00198 0.0562
SMAD3|SMAD3-R-V 0.002219 0.0562
YBX1|YB-1_PS102-R-V 0.002316 0.0562
SMAD1|SMAD1-R-V 0.002378 0.0562
YBX1|YB-1-R-V 0.005142 0.106
EGFR|EGFR_PY1068-R-C 0.006252 0.106
Clinical variable #11: 'NUMBER_OF_LYMPH_NODES'

2 genes related to 'NUMBER_OF_LYMPH_NODES'.

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

NUMBER_OF_LYMPH_NODES Mean (SD) 4.75 (6.3)
  Significant markers N = 2
  pos. correlated 0
  neg. correlated 2
List of 2 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

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

SpearmanCorr corrP Q
EIF4EBP1|4E-BP1-R-V -0.2253 0.000682 0.129
EIF4E|EIF4E-R-V -0.205 0.00204 0.193
Clinical variable #12: 'RACE'

30 genes related to 'RACE'.

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

RACE Labels N
  ASIAN 60
  BLACK OR AFRICAN AMERICAN 2
  WHITE 159
     
  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
SMAD3|SMAD3-R-V 5.539e-05 0.0105
PRDX1|PRDX1-R-V 0.0004264 0.0282
COL6A1|COLLAGEN_VI-R-V 0.0005148 0.0282
MS4A1|CD20-R-C 0.0005972 0.0282
RPTOR|RAPTOR-R-V 0.002473 0.0935
GATA3|GATA3-M-V 0.004195 0.127
ERBB2|HER2_PY1248-R-C 0.004901 0.127
CDH3|P-CADHERIN-R-C 0.005386 0.127
KIT|C-KIT-R-V 0.007885 0.154
MYH11|MYH11-R-V 0.008347 0.154
Methods & Data
Input

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

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

  • Number of patients = 264

  • Number of genes = 189

  • Number of clinical features = 12

Selected clinical features

  • For clinical features selected for this analysis and their value conozzle.versions, please find a documentation on selected CDEs .

  • 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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