Correlation between RPPA expression and clinical features
Sarcoma (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
doi:10.7908/C1CN7355
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/C1CN7355
Overview
Introduction

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

Summary

Testing the association between 192 genes and 9 clinical features across 222 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 7 clinical features related to at least one genes.

  • 30 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • CHEK1|CHK1 ,  MSH6|MSH6 ,  EIF4G1|EIF4G ,  MSH2|MSH2 ,  PRKAA1|AMPK_ALPHA ,  ...

  • 28 genes correlated to 'YEARS_TO_BIRTH'.

    • SERPINE1|PAI-1 ,  ANXA1|ANNEXIN-1 ,  PGR|PR ,  BRAF|B-RAF ,  PXN|PAXILLIN ,  ...

  • 30 genes correlated to 'TUMOR_TISSUE_SITE'.

    • CCNB1|CYCLIN_B1 ,  ACVRL1|ACVRL1 ,  SRC|SRC ,  ANXA1|ANNEXIN-1 ,  CASP7|CASPASE-7_CLEAVEDD198 ,  ...

  • 30 genes correlated to 'GENDER'.

    • YWHAB|14-3-3_BETA ,  MSH6|MSH6 ,  CHEK1|CHK1 ,  ERBB3|HER3_PY1289 ,  TFRC|TFRC ,  ...

  • 13 genes correlated to 'RADIATION_THERAPY'.

    • MYH11|MYH11 ,  CCNB1|CYCLIN_B1 ,  ACVRL1|ACVRL1 ,  SRC|SRC ,  RICTOR|RICTOR ,  ...

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • MYH11|MYH11 ,  RICTOR|RICTOR ,  AKT1 AKT2 AKT3|AKT_PS473 ,  GSK3A GSK3B|GSK3_PS9 ,  AKT1 AKT2 AKT3|AKT_PT308 ,  ...

  • 4 genes correlated to 'RESIDUAL_TUMOR'.

    • RAD50|RAD50 ,  TUBA1B|ACETYL-A-TUBULIN-LYS40 ,  TTF1|TTF1 ,  CAV1|CAVEOLIN-1

  • No genes correlated to 'RACE', and 'ETHNICITY'.

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=30 shorter survival N=20 longer survival N=10
YEARS_TO_BIRTH Spearman correlation test N=28 older N=15 younger N=13
TUMOR_TISSUE_SITE Kruskal-Wallis test N=30        
GENDER Wilcoxon test N=30 male N=30 female N=0
RADIATION_THERAPY Wilcoxon test N=13 yes N=13 no N=0
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
RESIDUAL_TUMOR Kruskal-Wallis test N=4        
RACE Kruskal-Wallis test   N=0        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

30 genes 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) 0.5-188.2 (median=25.4)
  censored N = 140
  death N = 81
     
  Significant markers N = 30
  associated with shorter survival 20
  associated with longer survival 10
List of top 10 genes differentially expressed by 'DAYS_TO_DEATH_OR_LAST_FUP'

Table S2.  Get Full Table List of top 10 genes significantly associated with 'Time to Death' by Cox regression test

HazardRatio Wald_P Q C_index
CHEK1|CHK1 3.7 3.234e-05 0.0062 0.62
MSH6|MSH6 2.5 0.0001288 0.0088 0.639
EIF4G1|EIF4G 2.7 0.0002048 0.0088 0.667
MSH2|MSH2 3.8 0.0002097 0.0088 0.62
PRKAA1|AMPK_ALPHA 0.23 0.0002284 0.0088 0.387
TUBA1B|ACETYL-A-TUBULIN-LYS40 1.78 0.000285 0.0091 0.627
EEF2K|EEF2K 2.4 0.0007417 0.02 0.596
RICTOR|RICTOR_PT1135 0.23 0.001634 0.039 0.376
RBM15|RBM15 1.89 0.002257 0.045 0.623
RPS6|S6 1.99 0.002351 0.045 0.645
Clinical variable #2: 'YEARS_TO_BIRTH'

28 genes related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 62 (14)
  Significant markers N = 28
  pos. correlated 15
  neg. correlated 13
List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

Table S4.  Get Full Table List of top 10 genes significantly correlated to 'YEARS_TO_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
SERPINE1|PAI-1 0.2698 4.842e-05 0.0093
ANXA1|ANNEXIN-1 0.2466 0.000213 0.0205
PGR|PR -0.2362 0.0003967 0.0254
BRAF|B-RAF 0.2209 0.0009452 0.0454
PXN|PAXILLIN 0.2101 0.001681 0.0646
MYH11|MYH11 -0.1983 0.003075 0.0984
NF2|NF2 0.1875 0.005177 0.126
ASNS|ASNS 0.1864 0.005445 0.126
EEF2|EEF2 0.1847 0.005889 0.126
ITGA2|CD49B -0.1791 0.00761 0.138
Clinical variable #3: 'TUMOR_TISSUE_SITE'

30 genes related to 'TUMOR_TISSUE_SITE'.

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

TUMOR_TISSUE_SITE Labels N
  CHEST - BREAST 1
  CHEST - CHEST WALL 6
  CHEST - LUNG/PLEURA 1
  CHEST - OTHER (PLEASE SPECIFY 2
  GYNECOLOGICAL - OVARY 1
  GYNECOLOGICAL - UTERUS 22
  HEAD AND NECK - HEAD 2
  HEAD AND NECK - OTHER (PLEASE SPECIFY 1
  LOWER ABDOMINAL/PELVIC - BLADDER 1
  LOWER ABDOMINAL/PELVIC - OTHER (PLEASE SPECIFY 1
  LOWER ABDOMINAL/PELVIC - PELVIC 11
  LOWER ABDOMINAL/PELVIC - SPERMATIC CORD 2
  LOWER EXTREMITY - FOOT/ANKLE 4
  LOWER EXTREMITY - GROIN 2
  LOWER EXTREMITY - LOWER LEG/CALF 15
  LOWER EXTREMITY - OTHER (PLEASE SPECIFY 5
  LOWER EXTREMITY - THIGH/KNEE 40
  RETROPERITONEUM/UPPER ABDOMINAL - COLON 3
  RETROPERITONEUM/UPPER ABDOMINAL - INTRAABDOMINAL 2
  RETROPERITONEUM/UPPER ABDOMINAL - KIDNEY 7
  RETROPERITONEUM/UPPER ABDOMINAL - OTHER (PLEASE SPECIFY 2
  RETROPERITONEUM/UPPER ABDOMINAL - PANCREAS 1
  RETROPERITONEUM/UPPER ABDOMINAL - RETROPERITONEUM 65
  RETROPERITONEUM/UPPER ABDOMINAL - SMALL INTESTINES 2
  SUPERFICIAL TRUNK - ABDOMINAL WALL 2
  SUPERFICIAL TRUNK - BACK 5
  SUPERFICIAL TRUNK - BUTTOCK 4
  UPPER EXTREMITY - SHOULDER/AXILLA 7
  UPPER EXTREMITY - UPPER ARM/ELBOW 4
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'TUMOR_TISSUE_SITE'

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

kruskal_wallis_P Q
CCNB1|CYCLIN_B1 2.382e-05 0.00457
ACVRL1|ACVRL1 8.515e-05 0.00501
SRC|SRC 9.838e-05 0.00501
ANXA1|ANNEXIN-1 0.0001043 0.00501
CASP7|CASPASE-7_CLEAVEDD198 0.0004707 0.0181
LCK|LCK 0.0006731 0.0213
RICTOR|RICTOR 0.0007783 0.0213
MYH9|MYOSIN-IIA_PS1943 0.001019 0.0226
BAX|BAX 0.001061 0.0226
CTNNB2|BETA-CATENIN 0.001957 0.0354
Clinical variable #4: 'GENDER'

30 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 117
  MALE 105
     
  Significant markers N = 30
  Higher in MALE 30
  Higher in FEMALE 0
List of top 10 genes differentially expressed by 'GENDER'

Table S8.  Get Full Table List of top 10 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
YWHAB|14-3-3_BETA 7859 0.0003289 0.0407 0.6397
MSH6|MSH6 4458 0.0004243 0.0407 0.6371
CHEK1|CHK1 4717 0.00286 0.129 0.616
ERBB3|HER3_PY1289 7544 0.003366 0.129 0.6141
TFRC|TFRC 4759 0.003798 0.129 0.6126
ANXA1|ANNEXIN-1 7487 0.00491 0.129 0.6094
BIRC2 |CIAP 7482 0.005072 0.129 0.609
WWTR1|TAZ 7443 0.006513 0.129 0.6059
EIF4EBP1|4E-BP1_PT37_T46 4846 0.00668 0.129 0.6055
BAX|BAX 7436 0.006807 0.129 0.6053
Clinical variable #5: 'RADIATION_THERAPY'

13 genes related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 158
  YES 59
     
  Significant markers N = 13
  Higher in YES 13
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATION_THERAPY'

Table S10.  Get Full Table List of top 10 genes differentially expressed by 'RADIATION_THERAPY'

W(pos if higher in 'YES') wilcoxontestP Q AUC
MYH11|MYH11 3096 0.0001437 0.0258 0.6679
CCNB1|CYCLIN_B1 6161 0.0002686 0.0258 0.6609
ACVRL1|ACVRL1 3345 0.00139 0.089 0.6412
SRC|SRC 3427 0.002723 0.0909 0.6324
RICTOR|RICTOR 3433 0.002856 0.0909 0.6317
YAP1|YAP 3435 0.002902 0.0909 0.6315
TSC1|TSC1 3453 0.003344 0.0909 0.6296
RAB25|RAB25 3469 0.003787 0.0909 0.6279
ERRFI1|MIG-6 5818 0.004949 0.0918 0.6241
FOXM1|FOXM1 5812 0.005178 0.0918 0.6235
Clinical variable #6: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  DEDIFFERENTIATED LIPOSARCOMA 54
  GIANT CELL 'MFH' / UNDIFFERENTIATED PLEOMORPHIC SARCOMA WITH GIANT CELLS 1
  LEIOMYOSARCOMA (LMS) 82
  MALIGNANT PERIPHERAL NERVE SHEATH TUMORS (MPNST) 9
  MYXOFIBROSARCOMA 22
  PLEOMORPHIC 'MFH'/ UNDIFFERENTIATED PLEOMORPHIC SARCOMA 29
  SARCOMA; SYNOVIAL; POORLY DIFFERENTIATED 1
  SYNOVIAL SARCOMA - BIPHASIC 1
  SYNOVIAL SARCOMA - MONOPHASIC 4
  UNDIFFERENTIATED PLEOMORPHIC SARCOMA (UPS) 19
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S12.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

kruskal_wallis_P Q
MYH11|MYH11 9.872e-19 1.9e-16
RICTOR|RICTOR 2.817e-18 2.7e-16
AKT1 AKT2 AKT3|AKT_PS473 1.866e-13 1.19e-11
GSK3A GSK3B|GSK3_PS9 6.459e-13 3.1e-11
AKT1 AKT2 AKT3|AKT_PT308 1.383e-12 5.31e-11
ANXA1|ANNEXIN-1 2.712e-12 8.68e-11
CASP7|CASPASE-7_CLEAVEDD198 1.881e-11 4.83e-10
CHEK1|CHK1_PS345 2.013e-11 4.83e-10
RAD50|RAD50 2.472e-11 5.27e-10
SRC|SRC 4.008e-11 7.69e-10
Clinical variable #7: 'RESIDUAL_TUMOR'

4 genes related to 'RESIDUAL_TUMOR'.

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

RESIDUAL_TUMOR Labels N
  R0 128
  R1 64
  R2 7
  RX 22
     
  Significant markers N = 4
List of 4 genes differentially expressed by 'RESIDUAL_TUMOR'

Table S14.  Get Full Table List of 4 genes differentially expressed by 'RESIDUAL_TUMOR'

kruskal_wallis_P Q
RAD50|RAD50 0.0002404 0.0462
TUBA1B|ACETYL-A-TUBULIN-LYS40 0.001451 0.139
TTF1|TTF1 0.002507 0.142
CAV1|CAVEOLIN-1 0.00295 0.142
Clinical variable #8: 'RACE'

No gene related to 'RACE'.

Table S15.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  ASIAN 6
  BLACK OR AFRICAN AMERICAN 13
  WHITE 195
     
  Significant markers N = 0
Clinical variable #9: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 3
  NOT HISPANIC OR LATINO 191
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 222

  • Number of genes = 192

  • Number of clinical features = 9

Selected clinical features

  • Further details on clinical features selected for this analysis, please find a documentation on selected CDEs (Clinical Data Elements). The first column of the file is a formula to convert values and the second column is a clinical parameter name.

  • 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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