Correlation between RPPA expression and clinical features
Rectum Adenocarcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C10P0Z3W
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Correlation between RPPA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C10P0Z3W
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 130 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 7 clinical features related to at least one genes.

  • 10 genes correlated to 'YEARS_TO_BIRTH'.

    • CCNB1|CYCLIN_B1-R-V ,  CAV1|CAVEOLIN-1-R-V ,  EIF4EBP1|4E-BP1_PS65-R-V ,  PTCH1|PTCH-R-C ,  PRKAA1|AMPK_PT172-R-V ,  ...

  • 1 gene correlated to 'NEOPLASM_DISEASESTAGE'.

    • PIK3CA|PI3K-P110-ALPHA-R-C

  • 2 genes correlated to 'PATHOLOGY_T_STAGE'.

    • BAX|BAX-R-V ,  CLDN7|CLAUDIN-7-R-V

  • 12 genes correlated to 'PATHOLOGY_N_STAGE'.

    • MYC|C-MYC-R-C ,  GAB2|GAB2-R-V ,  DVL3|DVL3-R-V ,  CCNE1|CYCLIN_E1-M-V ,  EIF4E|EIF4E-R-V ,  ...

  • 7 genes correlated to 'HISTOLOGICAL_TYPE'.

    • RAF1|C-RAF-R-V ,  RAB25|RAB25-R-C ,  BCL2L1|BCL-X-R-C ,  CDKN1B|P27-R-V ,  YAP1|YAP_PS127-R-C ,  ...

  • 1 gene correlated to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

    • PECAM1|CD31-M-V

  • 18 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

    • GAB2|GAB2-R-V ,  MYC|C-MYC-R-C ,  EIF4E|EIF4E-R-V ,  IRS1|IRS1-R-V ,  MAPK14|P38_PT180_Y182-R-V ,  ...

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'PATHOLOGY_M_STAGE', 'GENDER', 'COMPLETENESS_OF_RESECTION', 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
DAYS_TO_DEATH_OR_LAST_FUP Cox regression test   N=0        
YEARS_TO_BIRTH Spearman correlation test N=10 older N=7 younger N=3
NEOPLASM_DISEASESTAGE Kruskal-Wallis test N=1        
PATHOLOGY_T_STAGE Spearman correlation test N=2 higher stage N=0 lower stage N=2
PATHOLOGY_N_STAGE Spearman correlation test N=12 higher stage N=7 lower stage N=5
PATHOLOGY_M_STAGE Wilcoxon test   N=0        
GENDER Wilcoxon test   N=0        
HISTOLOGICAL_TYPE Wilcoxon test N=7 rectal mucinous adenocarcinoma N=7 rectal adenocarcinoma N=0
RADIATIONS_RADIATION_REGIMENINDICATION Wilcoxon test N=1 yes N=1 no N=0
COMPLETENESS_OF_RESECTION Kruskal-Wallis test   N=0        
NUMBER_OF_LYMPH_NODES Spearman correlation test N=18 higher number_of_lymph_nodes N=11 lower number_of_lymph_nodes N=7
RACE Kruskal-Wallis test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

No gene related to 'DAYS_TO_DEATH_OR_LAST_FUP'.

Table S1.  Basic characteristics of clinical feature: 'DAYS_TO_DEATH_OR_LAST_FUP'

DAYS_TO_DEATH_OR_LAST_FUP Duration (Months) 0.4-129.3 (median=16.8)
  censored N = 108
  death N = 21
     
  Significant markers N = 0
Clinical variable #2: 'YEARS_TO_BIRTH'

10 genes related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 65.57 (12)
  Significant markers N = 10
  pos. correlated 7
  neg. correlated 3
List of 10 genes differentially expressed by 'YEARS_TO_BIRTH'

Table S3.  Get Full Table List of 10 genes significantly correlated to 'YEARS_TO_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
CCNB1|CYCLIN_B1-R-V -0.2917 0.0007583 0.13
CAV1|CAVEOLIN-1-R-V 0.2636 0.00244 0.209
EIF4EBP1|4E-BP1_PS65-R-V 0.2365 0.006748 0.211
PTCH1|PTCH-R-C 0.2363 0.006807 0.211
PRKAA1|AMPK_PT172-R-V 0.2336 0.007479 0.211
PRKCA|PKC-ALPHA-M-V 0.2296 0.008608 0.211
CCNE1|CYCLIN_E1-M-V -0.2294 0.008646 0.211
SETD2|SETD2-R-NA -0.2198 0.012 0.234
BCL2L1|BCL-XL-R-V 0.2172 0.01304 0.234
PRKAA1|AMPK_ALPHA-R-C 0.2157 0.0137 0.234
Clinical variable #3: 'NEOPLASM_DISEASESTAGE'

One gene related to 'NEOPLASM_DISEASESTAGE'.

Table S4.  Basic characteristics of clinical feature: 'NEOPLASM_DISEASESTAGE'

NEOPLASM_DISEASESTAGE Labels N
  STAGE I 21
  STAGE II 7
  STAGE IIA 31
  STAGE IIB 1
  STAGE IIC 1
  STAGE III 6
  STAGE IIIA 8
  STAGE IIIB 19
  STAGE IIIC 10
  STAGE IV 16
  STAGE IVA 5
     
  Significant markers N = 1
List of one gene differentially expressed by 'NEOPLASM_DISEASESTAGE'

Table S5.  Get Full Table List of one gene differentially expressed by 'NEOPLASM_DISEASESTAGE'

kruskal_wallis_P Q
PIK3CA|PI3K-P110-ALPHA-R-C 0.001349 0.231
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) 2.82 (0.62)
  N
  T1 5
  T2 23
  T3 91
  T4 10
     
  Significant markers N = 2
  pos. correlated 0
  neg. correlated 2
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
BAX|BAX-R-V -0.2671 0.002216 0.2
CLDN7|CLAUDIN-7-R-V -0.2658 0.002334 0.2
Clinical variable #5: 'PATHOLOGY_N_STAGE'

12 genes related to 'PATHOLOGY_N_STAGE'.

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY_N_STAGE'

PATHOLOGY_N_STAGE Mean (SD) 0.7 (0.79)
  N
  N0 64
  N1 37
  N2 26
     
  Significant markers N = 12
  pos. correlated 7
  neg. correlated 5
List of top 10 genes differentially expressed by 'PATHOLOGY_N_STAGE'

Table S9.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_N_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
MYC|C-MYC-R-C 0.3046 0.0004981 0.0852
GAB2|GAB2-R-V 0.2799 0.001438 0.123
DVL3|DVL3-R-V 0.2435 0.005807 0.192
CCNE1|CYCLIN_E1-M-V -0.2361 0.007528 0.192
EIF4E|EIF4E-R-V -0.2352 0.007785 0.192
CASP7|CASPASE-7_CLEAVEDD198-R-C -0.2322 0.008611 0.192
PXN|PAXILLIN-R-V 0.2312 0.00893 0.192
ERBB2|HER2-M-V 0.231 0.008974 0.192
SRC|SRC_PY416-R-C -0.2265 0.01045 0.198
IRS1|IRS1-R-V 0.2235 0.01156 0.198
Clinical variable #6: 'PATHOLOGY_M_STAGE'

No gene related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 98
  class1 20
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

No gene related to 'GENDER'.

Table S11.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 60
  MALE 70
     
  Significant markers N = 0
Clinical variable #8: 'HISTOLOGICAL_TYPE'

7 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  RECTAL ADENOCARCINOMA 117
  RECTAL MUCINOUS ADENOCARCINOMA 10
     
  Significant markers N = 7
  Higher in RECTAL MUCINOUS ADENOCARCINOMA 7
  Higher in RECTAL ADENOCARCINOMA 0
List of 7 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S13.  Get Full Table List of 7 genes differentially expressed by 'HISTOLOGICAL_TYPE'

W(pos if higher in 'RECTAL MUCINOUS ADENOCARCINOMA') wilcoxontestP Q AUC
RAF1|C-RAF-R-V 981 0.0003997 0.0683 0.8385
RAB25|RAB25-R-C 956 0.0009115 0.0759 0.8171
BCL2L1|BCL-X-R-C 226 0.001332 0.0759 0.8068
CDKN1B|P27-R-V 267 0.004482 0.192 0.7718
YAP1|YAP_PS127-R-C 283 0.006958 0.238 0.7581
SETD2|SETD2-R-NA 876 0.009312 0.259 0.7487
RAD50|RAD50-M-C 299 0.0106 0.259 0.7444
Clinical variable #9: 'RADIATIONS_RADIATION_REGIMENINDICATION'

One gene related to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

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

RADIATIONS_RADIATION_REGIMENINDICATION Labels N
  NO 5
  YES 125
     
  Significant markers N = 1
  Higher in YES 1
  Higher in NO 0
List of one gene differentially expressed by 'RADIATIONS_RADIATION_REGIMENINDICATION'

Table S15.  Get Full Table List of one gene differentially expressed by 'RADIATIONS_RADIATION_REGIMENINDICATION'

W(pos if higher in 'YES') wilcoxontestP Q AUC
PECAM1|CD31-M-V 49 0.001453 0.248 0.9216
Clinical variable #10: 'COMPLETENESS_OF_RESECTION'

No gene related to 'COMPLETENESS_OF_RESECTION'.

Table S16.  Basic characteristics of clinical feature: 'COMPLETENESS_OF_RESECTION'

COMPLETENESS_OF_RESECTION Labels N
  R0 97
  R1 2
  R2 12
  RX 3
     
  Significant markers N = 0
Clinical variable #11: 'NUMBER_OF_LYMPH_NODES'

18 genes related to 'NUMBER_OF_LYMPH_NODES'.

Table S17.  Basic characteristics of clinical feature: 'NUMBER_OF_LYMPH_NODES'

NUMBER_OF_LYMPH_NODES Mean (SD) 2.44 (4.9)
  Significant markers N = 18
  pos. correlated 11
  neg. correlated 7
List of top 10 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

Table S18.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER_OF_LYMPH_NODES' by Spearman correlation test

SpearmanCorr corrP Q
GAB2|GAB2-R-V 0.3094 0.0004715 0.0806
MYC|C-MYC-R-C 0.2878 0.001192 0.0899
EIF4E|EIF4E-R-V -0.2771 0.001832 0.0899
IRS1|IRS1-R-V 0.2711 0.002323 0.0899
MAPK14|P38_PT180_Y182-R-V -0.2675 0.002668 0.0899
PXN|PAXILLIN-R-V 0.2618 0.003316 0.0899
SRC|SRC_PY416-R-C -0.2589 0.003694 0.0899
DVL3|DVL3-R-V 0.2553 0.004208 0.0899
MAP2K1|MEK1_PS217_S221-R-V -0.2383 0.007692 0.141
ERBB2|HER2-M-V 0.2362 0.008262 0.141
Clinical variable #12: 'RACE'

No gene related to 'RACE'.

Table S19.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  ASIAN 1
  BLACK OR AFRICAN AMERICAN 3
  WHITE 65
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 130

  • Number of genes = 171

  • Number of clinical features = 12

Selected clinical features

  • For clinical features selected for this analysis and their value conozzle.versions, please find a documentation on selected CDEs .

  • Survival time data

    • Survival time data is a combined value of days_to_death and days_to_last_followup. For each patient, it creates a combined value 'days_to_death_or_last_fup' using conversion process below.

      • if 'vital_status'==1(dead), 'days_to_last_followup' is always NA. Thus, uses 'days_to_death' value for 'days_to_death_or_fup'

      • if 'vital_status'==0(alive),

        • if 'days_to_death'==NA & 'days_to_last_followup'!=NA, uses 'days_to_last_followup' value for 'days_to_death_or_fup'

        • if 'days_to_death'!=NA, excludes this case in survival analysis and report the case.

      • if 'vital_status'==NA,excludes this case in survival analysis and report the case.

    • cf. In certain diesase types such as SKCM, days_to_death parameter is replaced with time_from_specimen_dx or time_from_specimen_procurement_to_death .

  • This analysis excluded clinical variables that has only NA values.

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

Wilcoxon rank sum test (Mann-Whitney U test)

For two groups (mutant or wild-type) of continuous type of clinical data, wilcoxon rank sum test (Mann and Whitney, 1947) was applied to compare their mean difference using 'wilcox.test(continuous.clinical ~ as.factor(group), exact=FALSE)' function in R. This test is equivalent to the Mann-Whitney test.

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] Mann and Whitney, On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other, Annals of Mathematical Statistics 18 (1), 50-60 (1947)
[4] 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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