Colon/Rectal Adenocarcinoma: Correlation between RPPA expression and clinical features
Maintained by Juok Cho (Broad Institute)
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 11 clinical features across 399 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

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

    • CHEK1|CHK1_PS345-R-C ,  BCL2|BCL-2-R-NA ,  BECN1|BECLIN-G-V ,  STK11|LKB1-M-NA ,  MRE11A|MRE11-R-C ,  ...

  • 59 genes correlated to 'HISTOLOGICAL.TYPE'.

    • CHEK1|CHK1_PS345-R-C ,  MRE11A|MRE11-R-C ,  STK11|LKB1-M-NA ,  ERBB3|HER3_PY1298-R-C ,  RAD51|RAD51-M-C ,  ...

  • 1 gene correlated to 'PATHOLOGY.T'.

    • ERRFI1|MIG-6-M-V

  • 8 genes correlated to 'PATHOLOGY.N'.

    • EIF4E|EIF4E-R-V ,  MYC|C-MYC-R-C ,  GAB2|GAB2-R-V ,  CASP7|CASPASE-7_CLEAVEDD198-R-C ,  MAPK14|P38_MAPK-R-C ,  ...

  • 7 genes correlated to 'TUMOR.STAGE'.

    • GAB2|GAB2-R-V ,  IRS1|IRS1-R-V ,  CCNE1|CYCLIN_E1-M-V ,  MAPK14|P38_MAPK-R-C ,  EIF4E|EIF4E-R-V ,  ...

  • No genes correlated to 'Time to Death', 'AGE', 'GENDER', 'PATHOLOGICSPREAD(M)', 'RADIATIONS.RADIATION.REGIMENINDICATION', and 'NEOADJUVANT.THERAPY'.

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=72 rectum N=0 colon N=72
GENDER t test   N=0        
HISTOLOGICAL TYPE ANOVA test N=59        
PATHOLOGY T Spearman correlation test N=1 higher pT N=1 lower pT N=0
PATHOLOGY N Spearman correlation test N=8 higher pN N=4 lower pN N=4
PATHOLOGICSPREAD(M) ANOVA test   N=0        
TUMOR STAGE Spearman correlation test N=7 higher stage N=3 lower stage N=4
RADIATIONS RADIATION REGIMENINDICATION t test   N=0        
NEOADJUVANT THERAPY t test   N=0        
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) 0.1-121.1 (median=6)
  censored N = 278
  death N = 30
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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

AGE Mean (SD) 66.25 (13)
  Significant markers N = 0
Clinical variable #3: 'PRIMARY.SITE.OF.DISEASE'

72 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 269
  RECTUM 130
     
  Significant markers N = 72
  Higher in RECTUM 0
  Higher in COLON 72
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 -10.22 2.183e-21 3.73e-19 0.7856
BCL2|BCL-2-R-NA -8.2 3.485e-15 5.92e-13 0.7344
BECN1|BECLIN-G-V -8.27 3.832e-15 6.48e-13 0.7405
STK11|LKB1-M-NA -8.23 8.774e-15 1.47e-12 0.7444
MRE11A|MRE11-R-C -8 3.144e-14 5.25e-12 0.7494
BID|BID-R-C -7.95 3.71e-14 6.16e-12 0.7238
RAD51|RAD51-M-C -7.94 6.061e-14 1e-11 0.7293
CDKN1B|P27_PT157-R-C -7.62 2.183e-13 3.58e-11 0.7401
BIRC2|CIAP-R-V -7.38 1.242e-12 2.03e-10 0.7211
XIAP|XIAP-R-C -7.14 7.44e-12 1.21e-09 0.7111

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 = 2.18e-21 with T-test analysis.

Clinical variable #4: 'GENDER'

No gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 187
  MALE 212
     
  Significant markers N = 0
Clinical variable #5: 'HISTOLOGICAL.TYPE'

59 genes related to 'HISTOLOGICAL.TYPE'.

Table S6.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  COLON ADENOCARCINOMA 238
  COLON MUCINOUS ADENOCARCINOMA 30
  RECTAL ADENOCARCINOMA 117
  RECTAL MUCINOUS ADENOCARCINOMA 10
     
  Significant markers N = 59
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S7.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
CHEK1|CHK1_PS345-R-C 1.94e-17 3.32e-15
MRE11A|MRE11-R-C 2.87e-14 4.88e-12
STK11|LKB1-M-NA 4.613e-14 7.8e-12
ERBB3|HER3_PY1298-R-C 6.278e-13 1.05e-10
RAD51|RAD51-M-C 1.324e-12 2.21e-10
BID|BID-R-C 1.825e-12 3.03e-10
BECN1|BECLIN-G-V 5.563e-12 9.18e-10
MET|C-MET_PY1235-R-C 4.25e-11 6.97e-09
XIAP|XIAP-R-C 7.054e-11 1.15e-08
PIK3R1|PI3K-P85-R-V 1.485e-10 2.41e-08

Figure S2.  Get High-res Image As an example, this figure shows the association of CHEK1|CHK1_PS345-R-C to 'HISTOLOGICAL.TYPE'. P value = 1.94e-17 with ANOVA analysis.

Clinical variable #6: 'PATHOLOGY.T'

One gene related to 'PATHOLOGY.T'.

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY.T'

PATHOLOGY.T Mean (SD) 2.88 (0.61)
  N
  T0 1
  T1 9
  T2 68
  T3 276
  T4 41
     
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

Table S9.  Get Full Table List of one gene significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

SpearmanCorr corrP Q
ERRFI1|MIG-6-M-V 0.1865 0.0001938 0.0331

Figure S3.  Get High-res Image As an example, this figure shows the association of ERRFI1|MIG-6-M-V to 'PATHOLOGY.T'. P value = 0.000194 with Spearman correlation analysis.

Clinical variable #7: 'PATHOLOGY.N'

8 genes related to 'PATHOLOGY.N'.

Table S10.  Basic characteristics of clinical feature: 'PATHOLOGY.N'

PATHOLOGY.N Mean (SD) 0.61 (0.76)
  N
  N0 224
  N1 103
  N2 68
     
  Significant markers N = 8
  pos. correlated 4
  neg. correlated 4
List of 8 genes significantly correlated to 'PATHOLOGY.N' by Spearman correlation test

Table S11.  Get Full Table List of 8 genes significantly correlated to 'PATHOLOGY.N' by Spearman correlation test

SpearmanCorr corrP Q
EIF4E|EIF4E-R-V -0.2215 8.875e-06 0.00152
MYC|C-MYC-R-C 0.21 2.583e-05 0.00439
GAB2|GAB2-R-V 0.2026 4.981e-05 0.00842
CASP7|CASPASE-7_CLEAVEDD198-R-C -0.2025 5.051e-05 0.00849
MAPK14|P38_MAPK-R-C -0.1971 8.038e-05 0.0134
PXN|PAXILLIN-R-V 0.1942 0.0001023 0.017
IRS1|IRS1-R-V 0.1866 0.0001914 0.0316
CCNE1|CYCLIN_E1-M-V -0.1866 0.0001919 0.0316

Figure S4.  Get High-res Image As an example, this figure shows the association of EIF4E|EIF4E-R-V to 'PATHOLOGY.N'. P value = 8.88e-06 with Spearman correlation analysis.

Clinical variable #8: 'PATHOLOGICSPREAD(M)'

No gene related to 'PATHOLOGICSPREAD(M)'.

Table S12.  Basic characteristics of clinical feature: 'PATHOLOGICSPREAD(M)'

PATHOLOGICSPREAD(M) Labels N
  M0 300
  M1 49
  M1A 8
  M1B 1
  MX 36
     
  Significant markers N = 0
Clinical variable #9: 'TUMOR.STAGE'

7 genes related to 'TUMOR.STAGE'.

Table S13.  Basic characteristics of clinical feature: 'TUMOR.STAGE'

TUMOR.STAGE Mean (SD) 2.45 (0.93)
  N
  Stage 1 61
  Stage 2 147
  Stage 3 119
  Stage 4 57
     
  Significant markers N = 7
  pos. correlated 3
  neg. correlated 4
List of 7 genes significantly correlated to 'TUMOR.STAGE' by Spearman correlation test

Table S14.  Get Full Table List of 7 genes significantly correlated to 'TUMOR.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
GAB2|GAB2-R-V 0.2101 3.317e-05 0.00567
IRS1|IRS1-R-V 0.1984 9.066e-05 0.0154
CCNE1|CYCLIN_E1-M-V -0.1949 0.0001216 0.0205
MAPK14|P38_MAPK-R-C -0.1885 0.0002023 0.034
EIF4E|EIF4E-R-V -0.1883 0.0002069 0.0346
PXN|PAXILLIN-R-V 0.1867 0.0002335 0.0388
CASP7|CASPASE-7_CLEAVEDD198-R-C -0.1835 0.0003014 0.0497

Figure S5.  Get High-res Image As an example, this figure shows the association of GAB2|GAB2-R-V to 'TUMOR.STAGE'. P value = 3.32e-05 with Spearman correlation 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 391
     
  Significant markers N = 0
Clinical variable #11: 'NEOADJUVANT.THERAPY'

No gene related to 'NEOADJUVANT.THERAPY'.

Table S16.  Basic characteristics of clinical feature: 'NEOADJUVANT.THERAPY'

NEOADJUVANT.THERAPY Labels N
  NO 68
  YES 331
     
  Significant markers N = 0
Methods & Data
Input

  • Expresson data file = COADREAD.rppa.txt

  • Clinical data file = COADREAD.clin.merged.picked.txt

  • Number of patients = 399

  • Number of genes = 171

  • Number of clinical features = 11

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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

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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