Correlation between RPPA expression and clinical features
Colon Adenocarcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1NV9H7B
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/C1NV9H7B
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, 9 clinical features related to at least one genes.

  • 1 gene correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • IGFBP2|IGFBP2-R-V

  • 7 genes correlated to 'YEARS_TO_BIRTH'.

    • BID|BID-R-C ,  SRC|SRC-M-V ,  RB1|RB_PS807_S811-R-V ,  CDKN1B|P27-R-V ,  MAP2K1|MEK1_PS217_S221-R-V ,  ...

  • 30 genes correlated to 'NEOPLASM_DISEASESTAGE'.

    • CASP7|CASPASE-7_CLEAVEDD198-R-C ,  NOTCH3|NOTCH3-R-C ,  PTK2|FAK-R-C ,  YAP1|YAP-R-V ,  PIK3CA|PI3K-P110-ALPHA-R-C ,  ...

  • 29 genes correlated to 'PATHOLOGY_T_STAGE'.

    • PTGS2|COX-2-R-C ,  NOTCH3|NOTCH3-R-C ,  ERRFI1|MIG-6-M-V ,  SRC|SRC_PY527-R-V ,  SRC|SRC-M-V ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • IRS1|IRS1-R-V ,  STK11|LKB1-M-NA ,  BCL2|BCL-2-R-NA ,  INPP4B|INPP4B-G-C ,  CASP7|CASPASE-7_CLEAVEDD198-R-C ,  ...

  • 6 genes correlated to 'PATHOLOGY_M_STAGE'.

    • CASP7|CASPASE-7_CLEAVEDD198-R-C ,  NCOA3|AIB1-M-V ,  PTK2|FAK-R-C ,  CCNE1|CYCLIN_E1-M-V ,  STK11|LKB1-M-NA ,  ...

  • 30 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 ,  ...

  • 30 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 ,  ...

  • 30 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

    • IRS1|IRS1-R-V ,  XRCC1|XRCC1-R-C ,  PXN|PAXILLIN-R-V ,  CASP7|CASPASE-7_CLEAVEDD198-R-C ,  STK11|LKB1-M-NA ,  ...

  • No genes correlated to '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
DAYS_TO_DEATH_OR_LAST_FUP Cox regression test N=1 shorter survival N=1 longer survival N=0
YEARS_TO_BIRTH Spearman correlation test N=7 older N=2 younger N=5
NEOPLASM_DISEASESTAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=29 higher stage N=12 lower stage N=17
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=17 lower stage N=13
PATHOLOGY_M_STAGE Wilcoxon test N=6 class1 N=6 class0 N=0
GENDER Wilcoxon test   N=0        
HISTOLOGICAL_TYPE Wilcoxon test N=30 colon mucinous adenocarcinoma N=30 colon adenocarcinoma N=0
RADIATIONS_RADIATION_REGIMENINDICATION Wilcoxon test   N=0        
COMPLETENESS_OF_RESECTION Kruskal-Wallis test N=30        
NUMBER_OF_LYMPH_NODES Spearman correlation test N=30 higher number_of_lymph_nodes N=14 lower number_of_lymph_nodes N=16
RACE Kruskal-Wallis test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

One 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) 0-140.4 (median=21)
  censored N = 262
  death N = 68
     
  Significant markers N = 1
  associated with shorter survival 1
  associated with longer survival 0
List of one gene differentially expressed by 'DAYS_TO_DEATH_OR_LAST_FUP'

Table S2.  Get Full Table List of one gene significantly associated with 'Time to Death' by Cox regression test

HazardRatio Wald_P Q C_index
IGFBP2|IGFBP2-R-V 1.4 0.001533 0.26 0.635
Clinical variable #2: 'YEARS_TO_BIRTH'

7 genes related to 'YEARS_TO_BIRTH'.

Table S3.  Basic characteristics of clinical feature: 'YEARS_TO_BIRTH'

YEARS_TO_BIRTH Mean (SD) 67.26 (13)
  Significant markers N = 7
  pos. correlated 2
  neg. correlated 5
List of 7 genes differentially expressed by 'YEARS_TO_BIRTH'

Table S4.  Get Full Table List of 7 genes significantly correlated to 'YEARS_TO_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
BID|BID-R-C -0.1836 0.0008025 0.0711
SRC|SRC-M-V -0.1831 0.0008319 0.0711
RB1|RB_PS807_S811-R-V 0.1754 0.001383 0.0788
CDKN1B|P27-R-V -0.1646 0.002709 0.105
MAP2K1|MEK1_PS217_S221-R-V 0.1624 0.003082 0.105
PEA15|PEA-15-R-V -0.1476 0.007218 0.199
YAP1|YAP-R-V -0.1454 0.008149 0.199
Clinical variable #3: 'NEOPLASM_DISEASESTAGE'

30 genes related to 'NEOPLASM_DISEASESTAGE'.

Table S5.  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 = 30
List of top 10 genes differentially expressed by 'NEOPLASM_DISEASESTAGE'

Table S6.  Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM_DISEASESTAGE'

kruskal_wallis_P Q
CASP7|CASPASE-7_CLEAVEDD198-R-C 9.463e-05 0.0147
NOTCH3|NOTCH3-R-C 0.0001714 0.0147
PTK2|FAK-R-C 0.0003457 0.0194
YAP1|YAP-R-V 0.000455 0.0194
PIK3CA|PI3K-P110-ALPHA-R-C 0.00186 0.0536
PXN|PAXILLIN-R-V 0.001881 0.0536
PRKAA1|AMPK_ALPHA-R-C 0.004674 0.114
ERRFI1|MIG-6-M-V 0.005793 0.124
NOTCH1|NOTCH1-R-V 0.009385 0.178
PRKAA1|AMPK_PT172-R-V 0.0122 0.209
Clinical variable #4: 'PATHOLOGY_T_STAGE'

29 genes related to 'PATHOLOGY_T_STAGE'.

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'

PATHOLOGY_T_STAGE Mean (SD) 2.92 (0.59)
  N
  T1 6
  T2 53
  T3 233
  T4 38
     
  Significant markers N = 29
  pos. correlated 12
  neg. correlated 17
List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S8.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
PTGS2|COX-2-R-C 0.2074 0.0001475 0.0252
NOTCH3|NOTCH3-R-C 0.1959 0.0003438 0.0294
ERRFI1|MIG-6-M-V 0.1705 0.001885 0.107
SRC|SRC_PY527-R-V -0.1654 0.002583 0.11
SRC|SRC-M-V -0.1603 0.003505 0.12
RB1|RB_PS807_S811-R-V -0.1538 0.005107 0.128
EIF4EBP1|4E-BP1_PT37-R-V -0.1533 0.005249 0.128
RAB25|RAB25-R-C 0.1441 0.008776 0.188
SRC|SRC_PY416-R-C -0.1387 0.01168 0.194
YBX1|YB-1_PS102-R-V -0.1358 0.01352 0.194
Clinical variable #5: 'PATHOLOGY_N_STAGE'

30 genes related to 'PATHOLOGY_N_STAGE'.

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY_N_STAGE'

PATHOLOGY_N_STAGE Mean (SD) 0.57 (0.76)
  N
  N0 196
  N1 80
  N2 55
     
  Significant markers N = 30
  pos. correlated 17
  neg. correlated 13
List of top 10 genes differentially expressed by 'PATHOLOGY_N_STAGE'

Table S10.  Get Full Table List of top 10 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 0.0689
BCL2|BCL-2-R-NA -0.1735 0.001532 0.0689
INPP4B|INPP4B-G-C 0.1646 0.002661 0.0689
CASP7|CASPASE-7_CLEAVEDD198-R-C -0.1639 0.002779 0.0689
EIF4E|EIF4E-R-V -0.1632 0.002897 0.0689
NCOA3|AIB1-M-V 0.1618 0.003152 0.0689
PXN|PAXILLIN-R-V 0.1612 0.003267 0.0689
BAX|BAX-R-V -0.1595 0.003624 0.0689
XRCC1|XRCC1-R-C -0.156 0.00444 0.07
Clinical variable #6: 'PATHOLOGY_M_STAGE'

6 genes related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 259
  class1 43
     
  Significant markers N = 6
  Higher in class1 6
  Higher in class0 0
List of 6 genes differentially expressed by 'PATHOLOGY_M_STAGE'

Table S12.  Get Full Table List of 6 genes differentially expressed by 'PATHOLOGY_M_STAGE'

W(pos if higher in 'class1') wilcoxontestP Q AUC
CASP7|CASPASE-7_CLEAVEDD198-R-C 3499 9.555e-05 0.0163 0.6858
NCOA3|AIB1-M-V 7344 0.0008163 0.0698 0.6594
PTK2|FAK-R-C 7245 0.001575 0.0898 0.6505
CCNE1|CYCLIN_E1-M-V 3956 0.002367 0.101 0.6448
STK11|LKB1-M-NA 4102 0.005701 0.195 0.6317
EIF4EBP1|4E-BP1_PT70-R-C 4176 0.008666 0.247 0.625
Clinical variable #7: 'GENDER'

No gene related to 'GENDER'.

Table S13.  Basic characteristics of clinical feature: 'GENDER'

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

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  COLON ADENOCARCINOMA 293
  COLON MUCINOUS ADENOCARCINOMA 38
     
  Significant markers N = 30
  Higher in COLON MUCINOUS ADENOCARCINOMA 30
  Higher in COLON ADENOCARCINOMA 0
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S15.  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 0.0021 0.716
RAD50|RAD50-M-C 3242 2.812e-05 0.0021 0.7088
MRE11A|MRE11-R-C 7858 3.676e-05 0.0021 0.7058
XRCC5|KU80-R-C 3347 6.361e-05 0.00272 0.6994
MET|C-MET_PY1235-R-C 7665 0.0001573 0.00538 0.6884
PDK1|PDK1_PS241-R-V 3495 0.0001897 0.00541 0.6861
HSPA1A|HSP70-R-C 7616 0.0002235 0.00546 0.684
AR|AR-R-V 7551.5 0.0003506 0.00678 0.6782
ANXA1|ANNEXIN_I-R-V 7549 0.0003567 0.00678 0.678
IGFBP2|IGFBP2-R-V 7512 0.0004592 0.00785 0.6747
Clinical variable #9: 'RADIATIONS_RADIATION_REGIMENINDICATION'

No gene related to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

Table S16.  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'

30 genes related to 'COMPLETENESS_OF_RESECTION'.

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

COMPLETENESS_OF_RESECTION Labels N
  R0 241
  R2 16
  RX 16
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'COMPLETENESS_OF_RESECTION'

Table S18.  Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS_OF_RESECTION'

kruskal_wallis_P Q
RPS6KB1|P70S6K_PT389-R-V 0.0002226 0.0189
STK11|LKB1-M-NA 0.0005258 0.0189
NCOA3|AIB1-M-V 0.0005446 0.0189
PEA15|PEA-15-R-V 0.0005448 0.0189
BCL2|BCL-2-R-NA 0.0006584 0.0189
EGFR|EGFR_PY1068-R-V 0.0006641 0.0189
CDKN1B|P27-R-V 0.001178 0.0244
PECAM1|CD31-M-V 0.001274 0.0244
MRE11A|MRE11-R-C 0.001286 0.0244
PIK3CA|PI3K-P110-ALPHA-R-C 0.001785 0.0286
Clinical variable #11: 'NUMBER_OF_LYMPH_NODES'

30 genes related to 'NUMBER_OF_LYMPH_NODES'.

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

NUMBER_OF_LYMPH_NODES Mean (SD) 1.96 (4.5)
  Significant markers N = 30
  pos. correlated 14
  neg. correlated 16
List of top 10 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

Table S20.  Get Full Table List of top 10 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 0.0598
PXN|PAXILLIN-R-V 0.1729 0.002213 0.105
CASP7|CASPASE-7_CLEAVEDD198-R-C -0.1709 0.002492 0.105
STK11|LKB1-M-NA -0.1635 0.003832 0.105
INPP4B|INPP4B-G-C 0.1634 0.003854 0.105
EIF4E|EIF4E-R-V -0.1615 0.004288 0.105
GAB2|GAB2-R-V 0.1532 0.006782 0.115
RPS6|S6_PS240_S244-R-V -0.1528 0.006933 0.115
ARID1A|ARID1A-M-V 0.152 0.007252 0.115
Clinical variable #12: 'RACE'

No gene related to 'RACE'.

Table S21.  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

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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