Correlation between RPPA expression and clinical features
Colorectal Adenocarcinoma (Primary solid tumor)
15 January 2014  |  analyses__2014_01_15
Maintainer Information
Citation Information
doi:10.7908/C15B00V8
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/C15B00V8
Overview
Introduction

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

Summary

Testing the association between 171 genes and 12 clinical features across 461 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.

  • 71 genes correlated to 'PRIMARY.SITE.OF.DISEASE'.

    • CHEK1|CHK1_PS345-R-C ,  BECN1|BECLIN-G-V ,  MRE11A|MRE11-R-C ,  STK11|LKB1-M-NA ,  BIRC2|CIAP-R-V ,  ...

  • 4 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • PIK3CA|PI3K-P110-ALPHA-R-C ,  CASP7|CASPASE-7_CLEAVEDD198-R-C ,  PTK2|FAK-R-C ,  PXN|PAXILLIN-R-V

  • 1 gene correlated to 'PATHOLOGY.T.STAGE'.

    • PTGS2|COX-2-R-C

  • 6 genes correlated to 'PATHOLOGY.N.STAGE'.

    • EIF4E|EIF4E-R-V ,  IRS1|IRS1-R-V ,  CASP7|CASPASE-7_CLEAVEDD198-R-C ,  PXN|PAXILLIN-R-V ,  BAX|BAX-R-V ,  ...

  • 69 genes correlated to 'HISTOLOGICAL.TYPE'.

    • ERBB3|HER3_PY1298-R-C ,  CHEK1|CHK1_PS345-R-C ,  MRE11A|MRE11-R-C ,  STK11|LKB1-M-NA ,  MET|C-MET_PY1235-R-C ,  ...

  • 1 gene correlated to 'COMPLETENESS.OF.RESECTION'.

    • PIK3CA|PI3K-P110-ALPHA-R-C

  • 7 genes correlated to 'NUMBER.OF.LYMPH.NODES'.

    • IRS1|IRS1-R-V ,  EIF4E|EIF4E-R-V ,  GAB2|GAB2-R-V ,  PXN|PAXILLIN-R-V ,  CASP7|CASPASE-7_CLEAVEDD198-R-C ,  ...

  • No genes correlated to 'Time to Death', 'AGE', 'PATHOLOGY.M.STAGE', 'GENDER', and 'RADIATIONS.RADIATION.REGIMENINDICATION'.

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=0        
PRIMARY SITE OF DISEASE t test N=71 rectum N=0 colon N=71
NEOPLASM DISEASESTAGE ANOVA test N=4        
PATHOLOGY T STAGE Spearman correlation test N=1 higher stage N=1 lower stage N=0
PATHOLOGY N STAGE Spearman correlation test N=6 higher stage N=3 lower stage N=3
PATHOLOGY M STAGE ANOVA test   N=0        
GENDER t test   N=0        
HISTOLOGICAL TYPE ANOVA test N=69        
RADIATIONS RADIATION REGIMENINDICATION t test   N=0        
COMPLETENESS OF RESECTION ANOVA test N=1        
NUMBER OF LYMPH NODES Spearman correlation test N=7 higher number.of.lymph.nodes N=3 lower number.of.lymph.nodes N=4
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) 0.1-140.4 (median=12.9)
  censored N = 317
  death N = 63
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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

AGE Mean (SD) 66.77 (13)
  Significant markers N = 0
Clinical variable #3: 'PRIMARY.SITE.OF.DISEASE'

71 genes related to 'PRIMARY.SITE.OF.DISEASE'.

Table S3.  Basic characteristics of clinical feature: 'PRIMARY.SITE.OF.DISEASE'

PRIMARY.SITE.OF.DISEASE Labels N
  COLON 331
  RECTUM 130
     
  Significant markers N = 71
  Higher in RECTUM 0
  Higher in COLON 71
List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

Table S4.  Get Full Table List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

T(pos if higher in 'RECTUM') ttestP Q AUC
CHEK1|CHK1_PS345-R-C -10.37 1.446e-21 2.47e-19 0.7802
BECN1|BECLIN-G-V -8.94 5.005e-17 8.51e-15 0.7512
MRE11A|MRE11-R-C -8.73 3.324e-16 5.62e-14 0.7655
STK11|LKB1-M-NA -8.76 4.033e-16 6.78e-14 0.755
BIRC2|CIAP-R-V -8.5 8.439e-16 1.41e-13 0.7421
XIAP|XIAP-R-C -8.31 4.718e-15 7.83e-13 0.7343
ERBB3|HER3_PY1298-R-C -8.36 9.841e-15 1.62e-12 0.7787
BID|BID-R-C -8.16 1.271e-14 2.09e-12 0.7227
AR|AR-R-V -7.9 4.786e-14 7.8e-12 0.7217
CDKN1B|P27_PT157-R-C -7.84 5.387e-14 8.73e-12 0.7387

Figure S1.  Get High-res Image As an example, this figure shows the association of CHEK1|CHK1_PS345-R-C to 'PRIMARY.SITE.OF.DISEASE'. P value = 1.45e-21 with T-test analysis.

Clinical variable #4: 'NEOPLASM.DISEASESTAGE'

4 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S5.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 70
  STAGE IA 1
  STAGE II 32
  STAGE IIA 134
  STAGE IIB 9
  STAGE IIC 2
  STAGE III 25
  STAGE IIIA 16
  STAGE IIIB 61
  STAGE IIIC 39
  STAGE IV 43
  STAGE IVA 19
  STAGE IVB 1
     
  Significant markers N = 4
List of 4 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S6.  Get Full Table List of 4 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
PIK3CA|PI3K-P110-ALPHA-R-C 1.829e-06 0.000313
CASP7|CASPASE-7_CLEAVEDD198-R-C 7.253e-06 0.00123
PTK2|FAK-R-C 0.0001135 0.0192
PXN|PAXILLIN-R-V 0.0002289 0.0384

Figure S2.  Get High-res Image As an example, this figure shows the association of PIK3CA|PI3K-P110-ALPHA-R-C to 'NEOPLASM.DISEASESTAGE'. P value = 1.83e-06 with ANOVA analysis.

Clinical variable #5: 'PATHOLOGY.T.STAGE'

One gene related to 'PATHOLOGY.T.STAGE'.

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.89 (0.6)
  N
  0 1
  1 10
  2 76
  3 324
  4 48
     
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

Table S8.  Get Full Table List of one gene significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
PTGS2|COX-2-R-C 0.1758 0.0001539 0.0263

Figure S3.  Get High-res Image As an example, this figure shows the association of PTGS2|COX-2-R-C to 'PATHOLOGY.T.STAGE'. P value = 0.000154 with Spearman correlation analysis.

Clinical variable #6: 'PATHOLOGY.N.STAGE'

6 genes related to 'PATHOLOGY.N.STAGE'.

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.61 (0.77)
  N
  0 260
  1 117
  2 81
     
  Significant markers N = 6
  pos. correlated 3
  neg. correlated 3
List of 6 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

Table S10.  Get Full Table List of 6 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
EIF4E|EIF4E-R-V -0.1987 1.844e-05 0.00315
IRS1|IRS1-R-V 0.1959 2.428e-05 0.00413
CASP7|CASPASE-7_CLEAVEDD198-R-C -0.1921 3.5e-05 0.00591
PXN|PAXILLIN-R-V 0.1773 0.0001371 0.023
BAX|BAX-R-V -0.1742 0.0001786 0.0298
MYC|C-MYC-R-C 0.1739 0.0001833 0.0304

Figure S4.  Get High-res Image As an example, this figure shows the association of EIF4E|EIF4E-R-V to 'PATHOLOGY.N.STAGE'. P value = 1.84e-05 with Spearman correlation analysis.

Clinical variable #7: '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
  M0 357
  M1 54
  M1A 8
  M1B 1
  MX 36
     
  Significant markers N = 0
Clinical variable #8: 'GENDER'

No gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 215
  MALE 246
     
  Significant markers N = 0
Clinical variable #9: 'HISTOLOGICAL.TYPE'

69 genes related to 'HISTOLOGICAL.TYPE'.

Table S13.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  COLON ADENOCARCINOMA 293
  COLON MUCINOUS ADENOCARCINOMA 38
  RECTAL ADENOCARCINOMA 117
  RECTAL MUCINOUS ADENOCARCINOMA 10
     
  Significant markers N = 69
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'

ANOVA_P Q
ERBB3|HER3_PY1298-R-C 7.189e-18 1.23e-15
CHEK1|CHK1_PS345-R-C 8.356e-18 1.42e-15
MRE11A|MRE11-R-C 1.774e-17 3e-15
STK11|LKB1-M-NA 5.059e-16 8.5e-14
MET|C-MET_PY1235-R-C 1.242e-14 2.07e-12
EGFR|EGFR_PY1173-R-C 2.095e-14 3.48e-12
AR|AR-R-V 7.511e-14 1.24e-11
XIAP|XIAP-R-C 9.227e-14 1.51e-11
BID|BID-R-C 1.885e-13 3.07e-11
BECN1|BECLIN-G-V 3.546e-13 5.74e-11

Figure S5.  Get High-res Image As an example, this figure shows the association of ERBB3|HER3_PY1298-R-C to 'HISTOLOGICAL.TYPE'. P value = 7.19e-18 with ANOVA analysis.

Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

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

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 8
  YES 453
     
  Significant markers N = 0
Clinical variable #11: 'COMPLETENESS.OF.RESECTION'

One gene related to 'COMPLETENESS.OF.RESECTION'.

Table S16.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 336
  R1 2
  R2 28
  RX 19
     
  Significant markers N = 1
List of one gene differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S17.  Get Full Table List of one gene differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
PIK3CA|PI3K-P110-ALPHA-R-C 0.0002037 0.0348

Figure S6.  Get High-res Image As an example, this figure shows the association of PIK3CA|PI3K-P110-ALPHA-R-C to 'COMPLETENESS.OF.RESECTION'. P value = 0.000204 with ANOVA analysis.

Clinical variable #12: 'NUMBER.OF.LYMPH.NODES'

7 genes related to 'NUMBER.OF.LYMPH.NODES'.

Table S18.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.1 (4.6)
  Significant markers N = 7
  pos. correlated 3
  neg. correlated 4
List of 7 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

Table S19.  Get Full Table List of 7 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
IRS1|IRS1-R-V 0.2271 1.705e-06 0.000292
EIF4E|EIF4E-R-V -0.2081 1.212e-05 0.00206
GAB2|GAB2-R-V 0.2012 2.373e-05 0.00401
PXN|PAXILLIN-R-V 0.1963 3.737e-05 0.00628
CASP7|CASPASE-7_CLEAVEDD198-R-C -0.1931 5.035e-05 0.00841
BAX|BAX-R-V -0.183 0.0001243 0.0206
XRCC1|XRCC1-R-C -0.1801 0.0001587 0.0262

Figure S7.  Get High-res Image As an example, this figure shows the association of IRS1|IRS1-R-V to 'NUMBER.OF.LYMPH.NODES'. P value = 1.71e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Methods & Data
Input

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

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

  • Number of patients = 461

  • Number of genes = 171

  • 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

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

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] 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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