Correlation between RPPA expression and clinical features
Bladder Urothelial Carcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
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/C1BV7FB9
Overview
Introduction

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

Summary

Testing the association between 179 genes and 11 clinical features across 127 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 8 clinical features related to at least one genes.

  • 1 gene correlated to 'NEOPLASM.DISEASESTAGE'.

    • SRC|SRC_PY416

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

    • RPS6|S6_PS240_S244 ,  YBX1|YB-1_PS102

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

    • CDH3|P-CADHERIN ,  BECN1|BECLIN ,  YWHAB|14-3-3_BETA ,  SYK|SYK ,  YWHAE|14-3-3_EPSILON ,  ...

  • 2 genes correlated to 'GENDER'.

    • MYH11|MYH11 ,  BAX|BAX

  • 1 gene correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

    • NFKB1|NF-KB-P65_PS536

  • 1 gene correlated to 'NUMBERPACKYEARSSMOKED'.

    • PDK1|PDK1_PS241

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

    • RPS6|S6_PS240_S244 ,  RPS6|S6_PS235_S236 ,  YBX1|YB-1_PS102 ,  RAB25|RAB25

  • 3 genes correlated to 'RACE'.

    • YBX1|YB-1 ,  FN1|FIBRONECTIN ,  CDH1|E-CADHERIN

  • No genes correlated to 'Time to Death', 'AGE', and 'PATHOLOGY.T.STAGE'.

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=0        
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=1        
PATHOLOGY T STAGE Spearman correlation test   N=0        
PATHOLOGY N STAGE Spearman correlation test N=2 higher stage N=0 lower stage N=2
PATHOLOGY M STAGE Kruskal-Wallis test N=7        
GENDER Wilcoxon test N=2 male N=2 female N=0
KARNOFSKY PERFORMANCE SCORE Spearman correlation test N=1 higher score N=0 lower score N=1
NUMBERPACKYEARSSMOKED Spearman correlation test N=1 higher numberpackyearssmoked N=1 lower numberpackyearssmoked N=0
NUMBER OF LYMPH NODES Spearman correlation test N=4 higher number.of.lymph.nodes N=1 lower number.of.lymph.nodes N=3
RACE Kruskal-Wallis test N=3        
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) 0.1-140.8 (median=9.3)
  censored N = 75
  death N = 47
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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

AGE Mean (SD) 67.15 (10)
  Significant markers N = 0
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

One gene related to 'NEOPLASM.DISEASESTAGE'.

Table S3.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 1
  STAGE II 36
  STAGE III 42
  STAGE IV 44
     
  Significant markers N = 1
List of one gene differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S4.  Get Full Table List of one gene differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
SRC|SRC_PY416 8.592e-05 0.0154
Clinical variable #4: 'PATHOLOGY.T.STAGE'

No gene related to 'PATHOLOGY.T.STAGE'.

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.92 (0.67)
  N
  1 1
  2 26
  3 63
  4 19
     
  Significant markers N = 0
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.69 (0.98)
  N
  0 71
  1 13
  2 24
  3 6
     
  Significant markers N = 2
  pos. correlated 0
  neg. correlated 2
List of 2 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S7.  Get Full Table List of 2 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
RPS6|S6_PS240_S244 -0.2983 0.001264 0.226
YBX1|YB-1_PS102 -0.295 0.001442 0.257
Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

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

PATHOLOGY.M.STAGE Labels N
  M0 73
  M1 5
  MX 48
     
  Significant markers N = 7
List of 7 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S9.  Get Full Table List of 7 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
CDH3|P-CADHERIN 2.949e-06 0.000528
BECN1|BECLIN 0.0001337 0.0238
YWHAB|14-3-3_BETA 0.0002896 0.0513
SYK|SYK 0.0004244 0.0747
YWHAE|14-3-3_EPSILON 0.0008737 0.153
KCNJ13|KIR7-1 0.0009022 0.157
NRAS|N-RAS 0.001115 0.193
Clinical variable #7: 'GENDER'

2 genes related to 'GENDER'.

Table S10.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 33
  MALE 94
     
  Significant markers N = 2
  Higher in MALE 2
  Higher in FEMALE 0
List of 2 genes differentially expressed by 'GENDER'

Table S11.  Get Full Table List of 2 genes differentially expressed by 'GENDER'. 0 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
MYH11|MYH11 901 0.0003561 0.0637 0.7095
BAX|BAX 953 0.001021 0.182 0.6928
Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

One gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S12.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 79.14 (16)
  Significant markers N = 1
  pos. correlated 0
  neg. correlated 1
List of one gene differentially expressed by 'KARNOFSKY.PERFORMANCE.SCORE'

Table S13.  Get Full Table List of one gene significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

SpearmanCorr corrP Q
NFKB1|NF-KB-P65_PS536 -0.5612 0.0004533 0.0811
Clinical variable #9: 'NUMBERPACKYEARSSMOKED'

One gene related to 'NUMBERPACKYEARSSMOKED'.

Table S14.  Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED Mean (SD) 36.76 (24)
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene differentially expressed by 'NUMBERPACKYEARSSMOKED'

Table S15.  Get Full Table List of one gene significantly correlated to 'NUMBERPACKYEARSSMOKED' by Spearman correlation test

SpearmanCorr corrP Q
PDK1|PDK1_PS241 0.3634 0.0009949 0.178
Clinical variable #10: 'NUMBER.OF.LYMPH.NODES'

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

Table S16.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 1.82 (3.8)
  Significant markers N = 4
  pos. correlated 1
  neg. correlated 3
List of 4 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S17.  Get Full Table List of 4 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
RPS6|S6_PS240_S244 -0.3948 0.0001175 0.021
RPS6|S6_PS235_S236 -0.3736 0.0002867 0.051
YBX1|YB-1_PS102 -0.3465 0.0008206 0.145
RAB25|RAB25 0.3281 0.001595 0.281
Clinical variable #11: 'RACE'

3 genes related to 'RACE'.

Table S18.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  ASIAN 8
  BLACK OR AFRICAN AMERICAN 9
  WHITE 100
     
  Significant markers N = 3
List of 3 genes differentially expressed by 'RACE'

Table S19.  Get Full Table List of 3 genes differentially expressed by 'RACE'

ANOVA_P Q
YBX1|YB-1 5.994e-05 0.0107
FN1|FIBRONECTIN 0.0005529 0.0984
CDH1|E-CADHERIN 0.001435 0.254
Methods & Data
Input
  • Expresson data file = BLCA-TP.rppa.txt

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

  • Number of patients = 127

  • Number of genes = 179

  • 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

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)