Correlation between RPPA expression and clinical features
Stomach Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C1VH5MNV
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between RPPA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1VH5MNV
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.

  • 4 genes correlated to 'Time to Death'.

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

  • 5 genes correlated to 'AGE'.

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

  • 6 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • CTNNA1|ALPHA-CATENIN-M-V ,  PEA15|PEA15-R-V ,  LCK|LCK-R-V ,  NDRG1|NDRG1_PT346-R-V ,  MS4A1|CD20-R-C ,  ...

  • 14 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.M.STAGE'.

    • DIRAS3|DI-RAS3-M-E ,  PGR|PR-R-V

  • 4 genes correlated to 'HISTOLOGICAL.TYPE'.

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

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

    • BID|BID-R-C ,  AR|AR-R-V ,  FN1|FIBRONECTIN-R-V ,  ESR1|ER-ALPHA-R-V ,  ACACA ACACB|ACC_PS79-R-V ,  ...

  • 4 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

  • 1 gene correlated to 'NUMBER.OF.LYMPH.NODES'.

    • EIF4EBP1|4E-BP1-R-V

  • 4 genes correlated to 'RACE'.

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

  • No genes correlated to 'PATHOLOGY.N.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
Time to Death Cox regression test N=4 shorter survival N=3 longer survival N=1
AGE Spearman correlation test N=5 older N=3 younger N=2
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=6        
PATHOLOGY T STAGE Spearman correlation test N=14 higher stage N=7 lower stage N=7
PATHOLOGY N STAGE Spearman correlation test   N=0        
PATHOLOGY M STAGE Kruskal-Wallis test N=2        
GENDER Wilcoxon test   N=0        
HISTOLOGICAL TYPE Kruskal-Wallis test N=4        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test N=6 yes N=6 no N=0
COMPLETENESS OF RESECTION Kruskal-Wallis test N=4        
NUMBER OF LYMPH NODES Spearman correlation test N=1 higher number.of.lymph.nodes N=0 lower number.of.lymph.nodes N=1
RACE Kruskal-Wallis test N=4        
Clinical variable #1: 'Time to Death'

4 genes related to 'Time to Death'.

Table S1.  Basic characteristics of clinical feature: 'Time to Death'

Time to Death Duration (Months) 0.1-105.1 (median=11)
  censored N = 162
  death N = 72
     
  Significant markers N = 4
  associated with shorter survival 3
  associated with longer survival 1
List of 4 genes differentially expressed by 'Time to Death'

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
EGFR|EGFR-R-V 2.5 4.403e-05 0.0083 0.638
DVL3|DVL3-R-V 5.4 0.0006245 0.12 0.642
ESR1|ER-ALPHA_PS118-R-V 12 0.00135 0.25 0.62
CDC2|CDK1-R-V 0.5 0.001371 0.25 0.381
Clinical variable #2: 'AGE'

5 genes related to 'AGE'.

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

AGE Mean (SD) 65.85 (11)
  Significant markers N = 5
  pos. correlated 3
  neg. correlated 2
List of 5 genes differentially expressed by 'AGE'

Table S4.  Get Full Table List of 5 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
CLDN7|CLAUDIN-7-R-V 0.2285 0.0002205 0.0417
SMAD1|SMAD1-R-V 0.2211 0.0003542 0.0666
PEA15|PEA15-R-V -0.2159 0.000491 0.0918
KIT|C-KIT-R-V -0.1969 0.001514 0.282
BIRC2 |CIAP-R-V 0.1965 0.001551 0.287
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

6 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 40
  STAGE IIIB 34
  STAGE IIIC 24
  STAGE IV 25
     
  Significant markers N = 6
List of 6 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S6.  Get Full Table List of 6 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
CTNNA1|ALPHA-CATENIN-M-V 2.556e-05 0.00483
PEA15|PEA15-R-V 6.102e-05 0.0115
LCK|LCK-R-V 0.0001862 0.0348
NDRG1|NDRG1_PT346-R-V 0.001127 0.21
MS4A1|CD20-R-C 0.001198 0.222
BIRC2 |CIAP-R-V 0.001323 0.243
Clinical variable #4: 'PATHOLOGY.T.STAGE'

14 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
  1 8
  2 67
  3 105
  4 74
     
  Significant markers N = 14
  pos. correlated 7
  neg. correlated 7
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 0.000569
BIRC2 |CIAP-R-V -0.2875 3.194e-06 6e-04
PEA15|PEA15-R-V 0.2524 4.718e-05 0.00882
CTNNA1|ALPHA-CATENIN-M-V -0.2499 5.655e-05 0.0105
RICTOR|RICTOR-R-C 0.2484 6.256e-05 0.0116
ACVRL1|ACVRL1-R-C 0.2477 6.572e-05 0.0121
MYH11|MYH11-R-V 0.245 7.944e-05 0.0145
BRCA2|BRCA2-R-C 0.2446 8.207e-05 0.0149
EIF4E|EIF4E-R-V -0.2327 0.0001826 0.033
BCL2|BCL-2-M-V 0.2304 0.0002121 0.0382
Clinical variable #5: 'PATHOLOGY.N.STAGE'

No gene 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
  0 87
  1 73
  2 42
  3 50
     
  Significant markers N = 0
Clinical variable #6: 'PATHOLOGY.M.STAGE'

2 genes related to 'PATHOLOGY.M.STAGE'.

Table S10.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 237
  M1 16
  MX 11
     
  Significant markers N = 2
List of 2 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S11.  Get Full Table List of 2 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
DIRAS3|DI-RAS3-M-E 0.0004018 0.0759
PGR|PR-R-V 0.0008921 0.168
Clinical variable #7: 'GENDER'

No gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 100
  MALE 164
     
  Significant markers N = 0
Clinical variable #8: 'HISTOLOGICAL.TYPE'

4 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 PAPILLARY TYPE 1
  STOMACH INTESTINAL ADENOCARCINOMA  MUCINOUS TYPE 16
  STOMACH INTESTINAL ADENOCARCINOMA  PAPILLARY TYPE 3
  STOMACH ADENOCARCINOMA SIGNET RING TYPE 2
     
  Significant markers N = 4
List of 4 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S14.  Get Full Table List of 4 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
MAPK8|JNK_PT183_PY185-R-V 0.0003982 0.0753
CTNNA1|ALPHA-CATENIN-M-V 0.000751 0.141
FASN|FASN-R-V 0.001136 0.212
RPS6|S6-R-E 0.001217 0.226
Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S15.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 7
  YES 257
     
  Significant markers N = 6
  Higher in YES 6
  Higher in NO 0
List of 6 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S16.  Get Full Table List of 6 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

W(pos if higher in 'YES') wilcoxontestP Q AUC
BID|BID-R-C 1596 0.0004796 0.0906 0.8872
AR|AR-R-V 1556 0.0009976 0.188 0.8649
FN1|FIBRONECTIN-R-V 1548 0.00115 0.215 0.8605
ESR1|ER-ALPHA-R-V 1540 0.001323 0.246 0.856
ACACA ACACB|ACC_PS79-R-V 262 0.001394 0.258 0.8544
BRCA2|BRCA2-R-C 1529 0.001601 0.295 0.8499
Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

4 genes related to 'COMPLETENESS.OF.RESECTION'.

Table S17.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 205
  R1 9
  R2 8
  RX 25
     
  Significant markers N = 4
List of 4 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S18.  Get Full Table List of 4 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
ESR1|ER-ALPHA_PS118-R-V 4.651e-06 0.000879
MET|C-MET_PY1235-R-V 9.983e-06 0.00188
BID|BID-R-C 0.0001387 0.0259
PKC|PKC-PAN_BETAII_PS660-R-V 0.001116 0.208
Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

One gene related to 'NUMBER.OF.LYMPH.NODES'.

Table S19.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 4.76 (6.3)
  Significant markers N = 1
  pos. correlated 0
  neg. correlated 1
List of one gene differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S20.  Get Full Table List of one gene significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
EIF4EBP1|4E-BP1-R-V -0.223 0.0007963 0.15
Clinical variable #12: 'RACE'

4 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 = 4
List of 4 genes differentially expressed by 'RACE'

Table S22.  Get Full Table List of 4 genes differentially expressed by 'RACE'

ANOVA_P Q
SMAD3|SMAD3-R-V 5.539e-05 0.0105
PRDX1|PRDX1-R-V 0.0004264 0.0802
COL6A1|COLLAGEN_VI-R-V 0.0005148 0.0963
MS4A1|CD20-R-C 0.0005972 0.111
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

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

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

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

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] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[4] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[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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