Correlation between mRNAseq expression and clinical features
Colorectal 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/C15M64WD
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 18041 genes and 14 clinical features across 620 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 12 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • MTERF|7978 ,  MGA|23269 ,  AMH|268 ,  ZNF75A|7627 ,  CNTD2|79935 ,  ...

  • 30 genes correlated to 'TUMOR_TISSUE_SITE'.

    • HOXB13|10481 ,  ZNF528|84436 ,  ELAVL2|1993 ,  HOXC6|3223 ,  HOXC4|3221 ,  ...

  • 30 genes correlated to 'PATHOLOGIC_STAGE'.

    • RGL2|5863 ,  GSR|2936 ,  C5ORF23|79614 ,  CASP1|834 ,  C13ORF15|28984 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • SCG2|7857 ,  C5ORF23|79614 ,  SOX11|6664 ,  OLR1|4973 ,  RBP7|116362 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • GSR|2936 ,  TEAD3|7005 ,  AGPAT5|55326 ,  C5ORF23|79614 ,  COQ2|27235 ,  ...

  • 30 genes correlated to 'PATHOLOGY_M_STAGE'.

    • LAP3|51056 ,  IRF1|3659 ,  GFI1|2672 ,  C13ORF15|28984 ,  CIITA|4261 ,  ...

  • 5 genes correlated to 'GENDER'.

    • CYORF15A|246126 ,  CYORF15B|84663 ,  HDHD1A|8226 ,  CA5BP|340591 ,  NCRNA00183|554203

  • 27 genes correlated to 'RADIATION_THERAPY'.

    • NCRNA00115|79854 ,  ZNF767|79970 ,  DOM3Z|1797 ,  VPS4B|9525 ,  MEX3C|51320 ,  ...

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • PLAGL2|5326 ,  POFUT1|23509 ,  MUC2|4583 ,  SLC5A6|8884 ,  TAF4|6874 ,  ...

  • 30 genes correlated to 'RESIDUAL_TUMOR'.

    • LOC150776|150776 ,  RRN3P2|653390 ,  POLR2J4|84820 ,  SPDYE8P|389517 ,  PMS2CL|441194 ,  ...

  • 30 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

    • GSR|2936 ,  C5ORF23|79614 ,  TEAD3|7005 ,  NPR3|4883 ,  CASP1|834 ,  ...

  • 30 genes correlated to 'RACE'.

    • C14ORF167|55449 ,  ULK4|54986 ,  CROCCL1|84809 ,  PPIL3|53938 ,  NOTCH2NL|388677 ,  ...

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 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=0        
YEARS_TO_BIRTH Spearman correlation test N=30 older N=11 younger N=19
TUMOR_TISSUE_SITE Wilcoxon test N=30 rectum N=30 colon N=0
PATHOLOGIC_STAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=29 lower stage N=1
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=11 lower stage N=19
PATHOLOGY_M_STAGE Wilcoxon test N=30 class1 N=30 class0 N=0
GENDER Wilcoxon test N=5 male N=5 female N=0
RADIATION_THERAPY Wilcoxon test N=27 yes N=27 no N=0
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
RESIDUAL_TUMOR Kruskal-Wallis test N=30        
NUMBER_OF_LYMPH_NODES Spearman correlation test N=30 higher number_of_lymph_nodes N=12 lower number_of_lymph_nodes N=18
RACE Kruskal-Wallis test N=30        
ETHNICITY Wilcoxon 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) 0-148 (median=20)
  censored N = 498
  death N = 121
     
  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) 66.37 (13)
  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
MTERF|7978 -0.2408 1.449e-09 2.02e-05
MGA|23269 -0.2376 2.24e-09 2.02e-05
AMH|268 0.2237 3.41e-08 0.000205
ZNF75A|7627 -0.2046 3.027e-07 0.00119
CNTD2|79935 0.2039 3.308e-07 0.00119
LOC154761|154761 0.1963 8.948e-07 0.00233
PPP1R10|5514 -0.1961 9.027e-07 0.00233
ZNF518B|85460 -0.1942 1.2e-06 0.00271
TGFBR2|7048 -0.1917 1.58e-06 0.00289
MRE11A|4361 -0.1918 1.602e-06 0.00289
Clinical variable #3: 'TUMOR_TISSUE_SITE'

30 genes related to 'TUMOR_TISSUE_SITE'.

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

TUMOR_TISSUE_SITE Labels N
  COLON 453
  RECTUM 163
     
  Significant markers N = 30
  Higher in RECTUM 30
  Higher in COLON 0
List of top 10 genes differentially expressed by 'TUMOR_TISSUE_SITE'

Table S5.  Get Full Table List of top 10 genes differentially expressed by 'TUMOR_TISSUE_SITE'

W(pos if higher in 'RECTUM') wilcoxontestP Q AUC
HOXB13|10481 52030 3.587e-15 6.47e-11 0.7078
ZNF528|84436 49064.5 2.286e-10 2.06e-06 0.6674
ELAVL2|1993 40172 3.82e-10 2.11e-06 0.6716
HOXC6|3223 16172 4.677e-10 2.11e-06 0.6832
HOXC4|3221 19444.5 6.359e-10 2.29e-06 0.6731
ZNF813|126017 48352 1.194e-09 3.59e-06 0.6607
ZNF662|389114 48254 1.636e-09 4.22e-06 0.6593
ZNF530|348327 48386 2.083e-09 4.7e-06 0.6582
ZNF141|7700 47993 2.698e-09 5.41e-06 0.6572
MAP7D2|256714 46784 3.908e-09 6.65e-06 0.6563
Clinical variable #4: 'PATHOLOGIC_STAGE'

30 genes related to 'PATHOLOGIC_STAGE'.

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

PATHOLOGIC_STAGE Labels N
  STAGE I 104
  STAGE IA 1
  STAGE II 37
  STAGE IIA 178
  STAGE IIB 11
  STAGE IIC 3
  STAGE III 27
  STAGE IIIA 18
  STAGE IIIB 83
  STAGE IIIC 54
  STAGE IV 62
  STAGE IVA 26
  STAGE IVB 2
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'PATHOLOGIC_STAGE'

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

kruskal_wallis_P Q
RGL2|5863 6.821e-10 1.23e-05
GSR|2936 6.962e-09 6.28e-05
C5ORF23|79614 2.02e-08 0.000121
CASP1|834 8.222e-08 0.000317
C13ORF15|28984 1.014e-07 0.000317
LAP3|51056 1.077e-07 0.000317
C2CD4A|145741 1.23e-07 0.000317
TMEM55A|55529 1.544e-07 0.000334
IRF1|3659 1.872e-07 0.000334
TEAD3|7005 1.89e-07 0.000334
Clinical variable #5: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

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

PATHOLOGY_T_STAGE Mean (SD) 2.88 (0.63)
  N
  T1 20
  T2 106
  T3 423
  T4 69
     
  Significant markers N = 30
  pos. correlated 29
  neg. correlated 1
List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

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

SpearmanCorr corrP Q
SCG2|7857 0.2571 1.04e-10 1.88e-06
C5ORF23|79614 0.2483 8.822e-10 7.96e-06
SOX11|6664 0.2414 2.226e-09 1.34e-05
OLR1|4973 0.2314 7.126e-09 1.77e-05
RBP7|116362 0.2302 8.122e-09 1.77e-05
CSRP2|1466 0.2292 8.302e-09 1.77e-05
NALCN|259232 0.2434 8.858e-09 1.77e-05
SPP1|6696 0.228 9.926e-09 1.77e-05
RIMKLB|57494 0.2279 1.014e-08 1.77e-05
ZFHX4|79776 0.2297 1.017e-08 1.77e-05
Clinical variable #6: 'PATHOLOGY_N_STAGE'

30 genes related to 'PATHOLOGY_N_STAGE'.

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

PATHOLOGY_N_STAGE Mean (SD) 0.62 (0.78)
  N
  N0 352
  N1 150
  N2 115
     
  Significant markers N = 30
  pos. correlated 11
  neg. correlated 19
List of top 10 genes differentially expressed by 'PATHOLOGY_N_STAGE'

Table S11.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_N_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
GSR|2936 -0.2886 2.65e-13 4.78e-09
TEAD3|7005 0.2696 9.869e-12 8.9e-08
AGPAT5|55326 -0.2581 7.645e-11 3.56e-07
C5ORF23|79614 0.2631 7.892e-11 3.56e-07
COQ2|27235 -0.2517 2.267e-10 8.18e-07
NPR3|4883 0.2675 4.377e-10 1.25e-06
NAT1|9 -0.2472 4.844e-10 1.25e-06
RGL2|5863 0.2459 6.018e-10 1.36e-06
CASP1|834 -0.2401 1.53e-09 3.07e-06
PBK|55872 -0.2396 1.715e-09 3.09e-06
Clinical variable #7: 'PATHOLOGY_M_STAGE'

30 genes related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 458
  class1 87
     
  Significant markers N = 30
  Higher in class1 30
  Higher in class0 0
List of top 10 genes differentially expressed by 'PATHOLOGY_M_STAGE'

Table S13.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY_M_STAGE'

W(pos if higher in 'class1') wilcoxontestP Q AUC
LAP3|51056 11507 4.104e-10 7.4e-06 0.7112
IRF1|3659 12258 1.254e-08 0.000113 0.6924
GFI1|2672 12593 5.225e-08 0.000314 0.684
C13ORF15|28984 26931 1.947e-07 0.000688 0.6759
CIITA|4261 12952 2.257e-07 0.000688 0.6749
WARS|7453 12969 2.414e-07 0.000688 0.6745
RARRES3|5920 13001 2.741e-07 0.000688 0.6737
IDO1|3620 12969 3.053e-07 0.000688 0.6731
TYMS|7298 13240 6.943e-07 0.00139 0.6677
CXCL9|4283 13274 7.905e-07 0.00143 0.6669
Clinical variable #8: 'GENDER'

5 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 289
  MALE 331
     
  Significant markers N = 5
  Higher in MALE 5
  Higher in FEMALE 0
List of 5 genes differentially expressed by 'GENDER'

Table S15.  Get Full Table List of 5 genes differentially expressed by 'GENDER'. 25 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
CYORF15A|246126 24807 6.508e-40 1.3e-36 0.9861
CYORF15B|84663 21234 1.52e-34 1.96e-31 0.9779
HDHD1A|8226 22577 7.457e-30 8.41e-27 0.764
CA5BP|340591 23915 6.046e-27 6.06e-24 0.75
NCRNA00183|554203 25843 5.002e-23 4.1e-20 0.7298
Clinical variable #9: 'RADIATION_THERAPY'

27 genes related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 454
  YES 29
     
  Significant markers N = 27
  Higher in YES 27
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATION_THERAPY'

Table S17.  Get Full Table List of top 10 genes differentially expressed by 'RADIATION_THERAPY'

W(pos if higher in 'YES') wilcoxontestP Q AUC
NCRNA00115|79854 9917 4.774e-06 0.0861 0.7532
ZNF767|79970 9589 3.717e-05 0.225 0.7283
DOM3Z|1797 9586 3.785e-05 0.225 0.7281
VPS4B|9525 3627 4.997e-05 0.225 0.7245
MEX3C|51320 3742 9.701e-05 0.286 0.7158
LY6G5B|58496 8855 0.000116 0.286 0.7171
C6ORF134|79969 9381 0.0001236 0.286 0.7125
LOC150197|150197 8920 0.0001416 0.286 0.7143
SOCS6|9306 3842 0.0001694 0.286 0.7082
SCARNA16|677781 6488 0.0001733 0.286 0.7287
Clinical variable #10: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

Table S18.  Basic characteristics of clinical feature: 'HISTOLOGICAL_TYPE'

HISTOLOGICAL_TYPE Labels N
  COLON ADENOCARCINOMA 388
  COLON MUCINOUS ADENOCARCINOMA 61
  RECTAL ADENOCARCINOMA 147
  RECTAL MUCINOUS ADENOCARCINOMA 13
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S19.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

kruskal_wallis_P Q
PLAGL2|5326 2.061e-21 3.72e-17
POFUT1|23509 2.97e-20 2.68e-16
MUC2|4583 3.153e-19 1.29e-15
SLC5A6|8884 3.418e-19 1.29e-15
TAF4|6874 3.683e-19 1.29e-15
SLC19A3|80704 4.304e-19 1.29e-15
KIAA0406|9675 1.115e-18 2.87e-15
SPDEF|25803 1.642e-18 3.7e-15
TOMM34|10953 2.03e-18 4.07e-15
SNHG11|128439 2.266e-18 4.09e-15
Clinical variable #11: 'RESIDUAL_TUMOR'

30 genes related to 'RESIDUAL_TUMOR'.

Table S20.  Basic characteristics of clinical feature: 'RESIDUAL_TUMOR'

RESIDUAL_TUMOR Labels N
  R0 449
  R1 5
  R2 36
  RX 30
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RESIDUAL_TUMOR'

Table S21.  Get Full Table List of top 10 genes differentially expressed by 'RESIDUAL_TUMOR'

kruskal_wallis_P Q
LOC150776|150776 4.66e-12 7.41e-08
RRN3P2|653390 1.032e-11 7.41e-08
POLR2J4|84820 1.821e-11 7.41e-08
SPDYE8P|389517 1.876e-11 7.41e-08
PMS2CL|441194 2.054e-11 7.41e-08
GUSBL2|375513 3.693e-11 1.08e-07
NSUN5P1|155400 4.194e-11 1.08e-07
GUSBL1|387036 5.413e-11 1.13e-07
STAG3L2|442582 6.304e-11 1.13e-07
AGAP11|119385 6.516e-11 1.13e-07
Clinical variable #12: 'NUMBER_OF_LYMPH_NODES'

30 genes related to 'NUMBER_OF_LYMPH_NODES'.

Table S22.  Basic characteristics of clinical feature: 'NUMBER_OF_LYMPH_NODES'

NUMBER_OF_LYMPH_NODES Mean (SD) 2.23 (4.7)
  Significant markers N = 30
  pos. correlated 12
  neg. correlated 18
List of top 10 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

Table S23.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER_OF_LYMPH_NODES' by Spearman correlation test

SpearmanCorr corrP Q
GSR|2936 -0.2843 2.674e-12 4.82e-08
C5ORF23|79614 0.269 1.054e-10 9.51e-07
TEAD3|7005 0.258 2.573e-10 1.18e-06
NPR3|4883 0.2783 2.625e-10 1.18e-06
CASP1|834 -0.2489 1.116e-09 3.5e-06
AGPAT5|55326 -0.2486 1.165e-09 3.5e-06
CXCL2|2920 -0.2444 2.24e-09 5.15e-06
COQ2|27235 -0.2443 2.285e-09 5.15e-06
SHC1|6464 0.2417 3.391e-09 6.8e-06
TCHH|7062 0.2462 4.593e-09 8.29e-06
Clinical variable #13: 'RACE'

30 genes related to 'RACE'.

Table S24.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 12
  BLACK OR AFRICAN AMERICAN 64
  WHITE 294
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S25.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
C14ORF167|55449 3.512e-14 5.77e-10
ULK4|54986 6.402e-14 5.77e-10
CROCCL1|84809 1.135e-13 6.83e-10
PPIL3|53938 4.629e-11 2.09e-07
NOTCH2NL|388677 6.944e-11 2.51e-07
SPDYE1|285955 1.097e-10 3.3e-07
RPS26|6231 3.333e-10 8.59e-07
SPDYE6|729597 5.482e-10 1.24e-06
POLR2J3|548644 8.955e-10 1.8e-06
LOC100190986|100190986 3.981e-09 7.18e-06
Clinical variable #14: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S26.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 5
  NOT HISPANIC OR LATINO 349
     
  Significant markers N = 0
Methods & Data
Input
  • Expresson data file = COADREAD-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt

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

  • Number of patients = 620

  • Number of genes = 18041

  • Number of clinical features = 14

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)