Correlation between RPPA expression and clinical features
Sarcoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C1CR5SVP
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between RPPA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1CR5SVP
Overview
Introduction

This pipeline uses various statistical tests to identify RPPAs whose expression levels correlated to selected clinical features. The input file "SARC-TP.rppa.txt" is generated in the pipeline RPPA_AnnotateWithGene in the stddata run.

Summary

Testing the association between 192 genes and 9 clinical features across 223 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'.

    • EIF4G1|EIF4G ,  RPS6|S6 ,  PRKAA1|AMPK_ALPHA ,  RBM15|RBM15 ,  ERBB3|HER3_PY1289 ,  ...

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

  • 30 genes correlated to 'GENDER'.

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

  • 23 genes correlated to 'RADIATION_THERAPY'.

    • CCNB1|CYCLIN_B1 ,  MYH11|MYH11 ,  ACVRL1|ACVRL1 ,  YAP1|YAP ,  SRC|SRC ,  ...

  • 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 ,  TTF1|TTF1 ,  TUBA1B|ACETYL-A-TUBULIN-LYS40 ,  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   N=NA   N=NA
YEARS_TO_BIRTH Spearman correlation test N=30 older N=17 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=23 yes N=23 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=30.3)
  censored N = 138
  death N = 84
     
  Significant markers N = 30
  associated with shorter survival NA
  associated with longer survival NA
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. For the survival curves, it compared quantile intervals at c(0, 0.25, 0.50, 0.75, 1) and did not try survival analysis if there is only one interval.

logrank_P Q C_index
EIF4G1|EIF4G 4.57e-06 0.00088 0.66
RPS6|S6 0.000393 0.022 0.643
PRKAA1|AMPK_ALPHA 0.000497 0.022 0.388
RBM15|RBM15 0.000557 0.022 0.627
ERBB3|HER3_PY1289 0.000579 0.022 0.415
TUBA1B|ACETYL-A-TUBULIN-LYS40 0.000735 0.023 0.636
CAV1|CAVEOLIN-1 0.00093 0.023 0.411
TP53|P53 0.000979 0.023 0.454
BAP1|BAP1-C-4 0.00133 0.026 0.624
CHEK1|CHK1 0.00136 0.026 0.619
Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 61.87 (14)
  Significant markers N = 30
  pos. correlated 17
  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 0.2704 4.459e-05 0.00856
ANXA1|ANNEXIN-1 0.2414 0.0002832 0.0196
PGR|PR -0.2401 0.0003057 0.0196
BRAF|B-RAF 0.2283 0.000609 0.0292
PXN|PAXILLIN 0.2127 0.001433 0.055
MYH11|MYH11 -0.2012 0.0026 0.0832
ASNS|ASNS 0.1952 0.003497 0.0959
NF2|NF2 0.1871 0.005158 0.124
ITGA2|CD49B -0.1846 0.005792 0.124
EEF2|EEF2 0.1809 0.006871 0.132
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 41
  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 4.507e-05 0.00478
SRC|SRC 7.901e-05 0.00478
ACVRL1|ACVRL1 8.02e-05 0.00478
ANXA1|ANNEXIN-1 9.953e-05 0.00478
CASP7|CASPASE-7_CLEAVEDD198 0.000443 0.017
LCK|LCK 0.0006361 0.0179
RICTOR|RICTOR 0.000652 0.0179
MYH9|MYOSIN-IIA_PS1943 0.0008925 0.0214
BAX|BAX 0.001002 0.0214
CTNNB2|BETA-CATENIN 0.001843 0.0338
Clinical variable #4: 'GENDER'

30 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 117
  MALE 106
     
  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
MSH6|MSH6 4465 0.0003098 0.0305 0.64
YWHAB|14-3-3_BETA 7934 0.0003173 0.0305 0.6397
CHEK1|CHK1 4722 0.00212 0.111 0.6193
TFRC|TFRC 4760 0.002755 0.111 0.6162
ERBB3|HER3_PY1289 7598 0.003703 0.111 0.6126
ANXA1|ANNEXIN-1 7571 0.004423 0.111 0.6105
BIRC2 |CIAP 7556 0.004876 0.111 0.6093
WWTR1|TAZ 7533 0.005652 0.111 0.6074
BAX|BAX 7507 0.006662 0.111 0.6053
CHEK2|CHK2 4899 0.006831 0.111 0.605
Clinical variable #5: 'RADIATION_THERAPY'

23 genes related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 156
  YES 62
     
  Significant markers N = 23
  Higher in YES 23
  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
CCNB1|CYCLIN_B1 6390 0.0002176 0.0213 0.6607
MYH11|MYH11 3284 0.0002218 0.0213 0.6605
ACVRL1|ACVRL1 3368 0.0004778 0.0306 0.6518
YAP1|YAP 3459 0.001052 0.0505 0.6424
SRC|SRC 3520 0.001741 0.0608 0.6361
RICTOR|RICTOR 3547 0.002163 0.0608 0.6333
RAB25|RAB25 3554 0.002287 0.0608 0.6325
TSC1|TSC1 3567 0.002534 0.0608 0.6312
EIF4EBP1|4E-BP1 6000 0.005617 0.12 0.6203
ERRFI1|MIG-6 5965 0.007231 0.135 0.6167
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 23
  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 1.086e-18 1.92e-16
RICTOR|RICTOR 2.005e-18 1.92e-16
AKT1 AKT2 AKT3|AKT_PS473 2.701e-13 1.73e-11
GSK3A GSK3B|GSK3_PS9 7.409e-13 3.56e-11
AKT1 AKT2 AKT3|AKT_PT308 2.091e-12 6.87e-11
ANXA1|ANNEXIN-1 2.148e-12 6.87e-11
CHEK1|CHK1_PS345 1.575e-11 4.32e-10
CASP7|CASPASE-7_CLEAVEDD198 1.824e-11 4.38e-10
RAD50|RAD50 2.11e-11 4.5e-10
SRC|SRC 2.817e-11 5.41e-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 65
  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 0.0002182 0.0419
TTF1|TTF1 0.001834 0.161
TUBA1B|ACETYL-A-TUBULIN-LYS40 0.00251 0.161
CAV1|CAVEOLIN-1 0.003494 0.168
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 196
     
  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 = 223

  • 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, logrank test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values comparing quantile intervals using the 'coxph' function in R. Kaplan-Meier survival curves were plotted using quantile intervals at c(0, 0.25, 0.50, 0.75, 1). If there is only one interval group, it will not try survival analysis.

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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