Correlation between mRNAseq expression and clinical features
Prostate Adenocarcinoma (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C13N22NN
Overview
Introduction

This pipeline uses various statistical tests to identify mRNAs whose log2 expression levels correlated to selected clinical features.

Summary

Testing the association between 18274 genes and 11 clinical features across 496 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 8 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • ADAP2|55803 ,  ARFGAP3|26286 ,  FCGR1A|2209 ,  TDP2|51567 ,  ELMO2|63916 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • ASPN|54829 ,  KCNK6|9424 ,  EPHX2|2053 ,  CHRNA2|1135 ,  FAM72A|729533 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • SPAG1|6674 ,  EDN3|1908 ,  RNF19A|25897 ,  SLC43A1|8501 ,  CECR6|27439 ,  ...

  • 30 genes correlated to 'RADIATION_THERAPY'.

    • KIAA0319L|79932 ,  PHYHIPL|84457 ,  DPT|1805 ,  CTHRC1|115908 ,  IGSF1|3547 ,  ...

  • 30 genes correlated to 'RESIDUAL_TUMOR'.

    • KIAA0319L|79932 ,  GEMIN4|50628 ,  CYP20A1|57404 ,  C15ORF58|390637 ,  C20ORF20|55257 ,  ...

  • 30 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

    • SPAG1|6674 ,  EDN3|1908 ,  RNF19A|25897 ,  FAM107A|11170 ,  ABCC5|10057 ,  ...

  • 30 genes correlated to 'GLEASON_SCORE'.

    • C15ORF42|90381 ,  FAM72B|653820 ,  FAM72D|728833 ,  TROAP|10024 ,  PRC1|9055 ,  ...

  • 30 genes correlated to 'PSA_VALUE'.

    • TLR8|51311 ,  TRIM59|286827 ,  PRR11|55771 ,  RPS27L|51065 ,  CYBB|1536 ,  ...

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'HISTOLOGICAL_TYPE', 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=30 older N=11 younger N=19
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=20 lower stage N=10
PATHOLOGY_N_STAGE Wilcoxon test N=30 n1 N=30 n0 N=0
RADIATION_THERAPY Wilcoxon test N=30 yes N=30 no N=0
HISTOLOGICAL_TYPE Wilcoxon test   N=0        
RESIDUAL_TUMOR 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
GLEASON_SCORE Spearman correlation test N=30 higher score N=28 lower score N=2
PSA_VALUE Spearman correlation test N=30 higher psa_value N=25 lower psa_value N=5
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) 0.7-165.2 (median=28.8)
  censored N = 485
  death N = 10
     
  Significant markers N = 0
Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 61.03 (6.8)
  Significant markers N = 30
  pos. correlated 11
  neg. correlated 19
List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

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

SpearmanCorr corrP Q
ADAP2|55803 0.3029 9.541e-12 1.74e-07
ARFGAP3|26286 -0.2427 6.22e-08 0.000546
FCGR1A|2209 0.2401 8.961e-08 0.000546
TDP2|51567 -0.2301 3.013e-07 0.00104
ELMO2|63916 -0.2293 3.324e-07 0.00104
KCNS1|3787 -0.2346 3.945e-07 0.00104
MNX1|3110 0.2292 3.974e-07 0.00104
HLX|3142 0.2265 4.65e-07 0.00106
ACSL3|2181 -0.2241 6.192e-07 0.00126
FBXL16|146330 0.2221 7.801e-07 0.00143
Clinical variable #3: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

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

PATHOLOGY_T_STAGE Mean (SD) 2.64 (0.52)
  N
  T2 188
  T3 292
  T4 10
     
  Significant markers N = 30
  pos. correlated 20
  neg. correlated 10
List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S5.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
ASPN|54829 0.3889 3.823e-19 6.99e-15
KCNK6|9424 -0.3841 1.135e-18 1.04e-14
EPHX2|2053 -0.3787 3.699e-18 2.25e-14
CHRNA2|1135 -0.3715 1.751e-17 8e-14
FAM72A|729533 0.3765 5.661e-17 2.07e-13
CIT|11113 0.3646 7.462e-17 2.11e-13
NAGLU|4669 -0.3642 8.064e-17 2.11e-13
COL10A1|1300 0.3583 3.119e-16 7.12e-13
CTHRC1|115908 0.3543 6.152e-16 1.11e-12
NEK2|4751 0.3545 6.276e-16 1.11e-12
Clinical variable #4: 'PATHOLOGY_N_STAGE'

30 genes related to 'PATHOLOGY_N_STAGE'.

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY_N_STAGE'

PATHOLOGY_N_STAGE Labels N
  N0 344
  N1 79
     
  Significant markers N = 30
  Higher in N1 30
  Higher in N0 0
List of top 10 genes differentially expressed by 'PATHOLOGY_N_STAGE'

Table S7.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY_N_STAGE'

W(pos if higher in 'N1') wilcoxontestP Q AUC
SPAG1|6674 20146 2.202e-11 4.02e-07 0.7413
EDN3|1908 6997 3.885e-09 3.55e-05 0.7186
RNF19A|25897 19235 8.299e-09 4.89e-05 0.7078
SLC43A1|8501 8000 1.184e-08 4.89e-05 0.7056
CECR6|27439 8050 1.595e-08 4.89e-05 0.7038
GNE|10020 8051 1.604e-08 4.89e-05 0.7037
FAM107A|11170 8107 2.233e-08 5.83e-05 0.7017
PROK1|84432 8146 3.252e-08 7.43e-05 0.6994
MBD4|8930 18956 4.312e-08 8.16e-05 0.6975
ABCC5|10057 18950 4.464e-08 8.16e-05 0.6973
Clinical variable #5: 'RADIATION_THERAPY'

30 genes related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 382
  YES 57
     
  Significant markers N = 30
  Higher in YES 30
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATION_THERAPY'

Table S9.  Get Full Table List of top 10 genes differentially expressed by 'RADIATION_THERAPY'

W(pos if higher in 'YES') wilcoxontestP Q AUC
KIAA0319L|79932 6317 3.153e-07 0.00495 0.7099
PHYHIPL|84457 6409 5.413e-07 0.00495 0.7057
DPT|1805 6511 9.735e-07 0.00529 0.701
CTHRC1|115908 15203 1.367e-06 0.00529 0.6982
IGSF1|3547 6492 1.782e-06 0.00529 0.6963
RNF185|91445 6686 2.588e-06 0.00529 0.6929
SPATA4|132851 5993 2.884e-06 0.00529 0.6985
YIPF1|54432 6714 3.016e-06 0.00529 0.6917
GNG4|2786 6724 3.185e-06 0.00529 0.6912
MMP11|4320 15046 3.255e-06 0.00529 0.691
Clinical variable #6: 'HISTOLOGICAL_TYPE'

No gene related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  PROSTATE ADENOCARCINOMA OTHER SUBTYPE 15
  PROSTATE ADENOCARCINOMA ACINAR TYPE 481
     
  Significant markers N = 0
Clinical variable #7: 'RESIDUAL_TUMOR'

30 genes related to 'RESIDUAL_TUMOR'.

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

RESIDUAL_TUMOR Labels N
  R0 314
  R1 146
  R2 5
  RX 15
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RESIDUAL_TUMOR'

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

kruskal_wallis_P Q
KIAA0319L|79932 1.582e-08 0.000165
GEMIN4|50628 1.811e-08 0.000165
CYP20A1|57404 3.526e-08 0.000215
C15ORF58|390637 5.286e-08 0.00023
C20ORF20|55257 6.322e-08 0.00023
VPS36|51028 7.55e-08 0.00023
CNIH2|254263 1.217e-07 0.000312
TROAP|10024 1.583e-07 0.000312
ZNRF3|84133 1.656e-07 0.000312
ZBED1|9189 2.052e-07 0.000312
Clinical variable #8: 'NUMBER_OF_LYMPH_NODES'

30 genes related to 'NUMBER_OF_LYMPH_NODES'.

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

NUMBER_OF_LYMPH_NODES Mean (SD) 0.44 (1.4)
  Significant markers N = 30
  pos. correlated 14
  neg. correlated 16
List of top 10 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

Table S14.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER_OF_LYMPH_NODES' by Spearman correlation test

SpearmanCorr corrP Q
SPAG1|6674 0.3384 2.636e-12 4.82e-08
EDN3|1908 -0.3183 1.108e-10 1.01e-06
RNF19A|25897 0.2983 9.142e-10 4.34e-06
FAM107A|11170 -0.298 9.494e-10 4.34e-06
ABCC5|10057 0.2958 1.28e-09 4.68e-06
PROK1|84432 -0.2902 2.805e-09 8.54e-06
MBD4|8930 0.2881 3.523e-09 9.2e-06
CECR6|27439 -0.2856 4.867e-09 1.11e-05
PEBP4|157310 -0.2838 6.374e-09 1.18e-05
CHRNA2|1135 -0.2833 6.476e-09 1.18e-05
Clinical variable #9: 'GLEASON_SCORE'

30 genes related to 'GLEASON_SCORE'.

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

GLEASON_SCORE Mean (SD) 7.61 (1)
  Score N
  6 45
  7 247
  8 64
  9 136
  10 4
     
  Significant markers N = 30
  pos. correlated 28
  neg. correlated 2
List of top 10 genes differentially expressed by 'GLEASON_SCORE'

Table S16.  Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE' by Spearman correlation test

SpearmanCorr corrP Q
C15ORF42|90381 0.4901 2.445e-31 3.47e-27
FAM72B|653820 0.4888 3.799e-31 3.47e-27
FAM72D|728833 0.4712 8.851e-29 5.39e-25
TROAP|10024 0.4687 1.864e-28 8.52e-25
PRC1|9055 0.4648 5.885e-28 2.15e-24
KIF23|9493 0.4615 1.579e-27 4.81e-24
SPAG5|10615 0.4599 2.484e-27 6.49e-24
UBE2C|11065 0.4586 3.628e-27 7.96e-24
NUF2|83540 0.4583 3.918e-27 7.96e-24
FAM72A|729533 0.47 4.934e-27 9.02e-24
Clinical variable #10: 'PSA_VALUE'

30 genes related to 'PSA_VALUE'.

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

PSA_VALUE Mean (SD) 1.79 (16)
  Significant markers N = 30
  pos. correlated 25
  neg. correlated 5
List of top 10 genes differentially expressed by 'PSA_VALUE'

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

SpearmanCorr corrP Q
TLR8|51311 0.2544 7.431e-08 0.000379
TRIM59|286827 0.2526 8.084e-08 0.000379
PRR11|55771 0.2602 8.088e-08 0.000379
RPS27L|51065 -0.2524 8.3e-08 0.000379
CYBB|1536 0.244 2.255e-07 0.000677
ARHGEF3|50650 0.2425 2.707e-07 0.000677
DYRK2|8445 0.2418 2.918e-07 0.000677
CST3|1471 -0.2417 2.965e-07 0.000677
NCOA3|8202 0.2389 4.11e-07 0.000678
PLXNC1|10154 0.24 4.206e-07 0.000678
Clinical variable #11: 'RACE'

No gene related to 'RACE'.

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

RACE Labels N
  ASIAN 2
  BLACK OR AFRICAN AMERICAN 7
  WHITE 147
     
  Significant markers N = 0
Methods & Data
Input
  • Expresson data file = PRAD-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt

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

  • Number of patients = 496

  • Number of genes = 18274

  • Number of clinical features = 11

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)