Correlation between RPPA expression and clinical features
Colon Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C1SJ1J9R
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/C1SJ1J9R
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 331 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 8 clinical features related to at least one genes.

  • 3 genes correlated to 'AGE'.

    • BID|BID-R-C ,  SRC|SRC-M-V ,  RB1|RB_PS807_S811-R-V

  • 4 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • CASP7|CASPASE-7_CLEAVEDD198-R-C ,  NOTCH3|NOTCH3-R-C ,  PTK2|FAK-R-C ,  YAP1|YAP-R-V

  • 2 genes correlated to 'PATHOLOGY.T.STAGE'.

    • PTGS2|COX-2-R-C ,  NOTCH3|NOTCH3-R-C

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

    • IRS1|IRS1-R-V ,  STK11|LKB1-M-NA ,  BCL2|BCL-2-R-NA

  • 2 genes correlated to 'PATHOLOGY.M.STAGE'.

    • CASP7|CASPASE-7_CLEAVEDD198-R-C ,  IGFBP2|IGFBP2-R-V

  • 19 genes correlated to 'HISTOLOGICAL.TYPE'.

    • BAK1|BAK-R-C ,  RAD50|RAD50-M-C ,  MRE11A|MRE11-R-C ,  XRCC5|KU80-R-C ,  MET|C-MET_PY1235-R-C ,  ...

  • 11 genes correlated to 'COMPLETENESS.OF.RESECTION'.

    • RPS6KB1|P70S6K_PT389-R-V ,  STK11|LKB1-M-NA ,  NCOA3|AIB1-M-V ,  PEA15|PEA-15-R-V ,  BCL2|BCL-2-R-NA ,  ...

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

    • IRS1|IRS1-R-V ,  XRCC1|XRCC1-R-C

  • No genes correlated to 'Time to Death', 'GENDER', 'RADIATIONS.RADIATION.REGIMENINDICATION', and 'RACE'.

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=0        
AGE Spearman correlation test N=3 older N=1 younger N=2
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=4        
PATHOLOGY T STAGE Spearman correlation test N=2 higher stage N=2 lower stage N=0
PATHOLOGY N STAGE Spearman correlation test N=3 higher stage N=1 lower stage N=2
PATHOLOGY M STAGE Kruskal-Wallis test N=2        
GENDER Wilcoxon test   N=0        
HISTOLOGICAL TYPE Wilcoxon test N=19 colon mucinous adenocarcinoma N=19 colon adenocarcinoma N=0
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test   N=0        
COMPLETENESS OF RESECTION Kruskal-Wallis test N=11        
NUMBER OF LYMPH NODES Spearman correlation test N=2 higher number.of.lymph.nodes N=1 lower number.of.lymph.nodes N=1
RACE Kruskal-Wallis 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) 0.1-140.4 (median=20.3)
  censored N = 254
  death N = 65
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

3 genes related to 'AGE'.

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

AGE Mean (SD) 67.26 (13)
  Significant markers N = 3
  pos. correlated 1
  neg. correlated 2
List of 3 genes differentially expressed by 'AGE'

Table S3.  Get Full Table List of 3 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
BID|BID-R-C -0.1836 0.0008025 0.137
SRC|SRC-M-V -0.1831 0.0008319 0.141
RB1|RB_PS807_S811-R-V 0.1754 0.001383 0.234
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

4 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S4.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 49
  STAGE IA 1
  STAGE II 20
  STAGE IIA 108
  STAGE IIB 8
  STAGE IIC 1
  STAGE III 18
  STAGE IIIA 8
  STAGE IIIB 43
  STAGE IIIC 29
  STAGE IV 28
  STAGE IVA 14
  STAGE IVB 1
     
  Significant markers N = 4
List of 4 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S5.  Get Full Table List of 4 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
CASP7|CASPASE-7_CLEAVEDD198-R-C 9.463e-05 0.0162
NOTCH3|NOTCH3-R-C 0.0001714 0.0291
PTK2|FAK-R-C 0.0003457 0.0584
YAP1|YAP-R-V 0.000455 0.0764
Clinical variable #4: 'PATHOLOGY.T.STAGE'

2 genes related to 'PATHOLOGY.T.STAGE'.

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.92 (0.6)
  N
  0 1
  1 5
  2 53
  3 233
  4 38
     
  Significant markers N = 2
  pos. correlated 2
  neg. correlated 0
List of 2 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S7.  Get Full Table List of 2 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
PTGS2|COX-2-R-C 0.2074 0.0001481 0.0253
NOTCH3|NOTCH3-R-C 0.196 0.0003419 0.0581
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.57 (0.76)
  N
  0 196
  1 80
  2 55
     
  Significant markers N = 3
  pos. correlated 1
  neg. correlated 2
List of 3 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S9.  Get Full Table List of 3 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
IRS1|IRS1-R-V 0.2159 7.482e-05 0.0128
STK11|LKB1-M-NA -0.18 0.001005 0.171
BCL2|BCL-2-R-NA -0.1735 0.001532 0.259
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 259
  M1 36
  M1A 6
  M1B 1
  MX 26
     
  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
CASP7|CASPASE-7_CLEAVEDD198-R-C 0.0009987 0.171
IGFBP2|IGFBP2-R-V 0.0009972 0.171
Clinical variable #7: 'GENDER'

No gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 155
  MALE 176
     
  Significant markers N = 0
Clinical variable #8: 'HISTOLOGICAL.TYPE'

19 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
     
  Significant markers N = 19
  Higher in COLON MUCINOUS ADENOCARCINOMA 19
  Higher in COLON ADENOCARCINOMA 0
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'

W(pos if higher in 'COLON MUCINOUS ADENOCARCINOMA') wilcoxontestP Q AUC
BAK1|BAK-R-C 7972 1.475e-05 0.00252 0.716
RAD50|RAD50-M-C 3242 2.812e-05 0.00478 0.7088
MRE11A|MRE11-R-C 7858 3.676e-05 0.00621 0.7058
XRCC5|KU80-R-C 3347 6.361e-05 0.0107 0.6994
MET|C-MET_PY1235-R-C 7665 0.0001573 0.0263 0.6884
PDK1|PDK1_PS241-R-V 3495 0.0001897 0.0315 0.6861
HSPA1A|HSP70-R-C 7616 0.0002235 0.0369 0.684
AR|AR-R-V 7551.5 0.0003506 0.0575 0.6782
ANXA1|ANNEXIN_I-R-V 7549 0.0003567 0.0581 0.678
IGFBP2|IGFBP2-R-V 7512 0.0004592 0.0744 0.6747
Clinical variable #9: '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 3
  YES 328
     
  Significant markers N = 0
Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

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

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

COMPLETENESS.OF.RESECTION Labels N
  R0 241
  R2 16
  RX 16
     
  Significant markers N = 11
List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

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

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

NUMBER.OF.LYMPH.NODES Mean (SD) 1.96 (4.5)
  Significant markers N = 2
  pos. correlated 1
  neg. correlated 1
List of 2 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S19.  Get Full Table List of 2 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
IRS1|IRS1-R-V 0.2401 1.865e-05 0.00319
XRCC1|XRCC1-R-C -0.1912 0.0006993 0.119
Clinical variable #12: 'RACE'

No gene related to 'RACE'.

Table S20.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 11
  BLACK OR AFRICAN AMERICAN 21
  WHITE 181
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 331

  • 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

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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