Correlation between mRNAseq expression and clinical features
Colorectal Adenocarcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
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/C1B8574H
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 13 clinical features across 616 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 11 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • MTERF|7978 ,  MGA|23269 ,  AMH|268 ,  CNTD2|79935 ,  LOC154761|154761 ,  ...

  • 30 genes correlated to 'PRIMARY_SITE_OF_DISEASE'.

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

  • 30 genes correlated to 'NEOPLASM_DISEASESTAGE'.

    • RGL2|5863 ,  C5ORF23|79614 ,  GSR|2936 ,  C2CD4A|145741 ,  LAP3|51056 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • SCG2|7857 ,  C5ORF23|79614 ,  SOX11|6664 ,  SPP1|6696 ,  OLR1|4973 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

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

  • 30 genes correlated to 'PATHOLOGY_M_STAGE'.

    • LAP3|51056 ,  IRF1|3659 ,  GFI1|2672 ,  WARS|7453 ,  RARRES3|5920 ,  ...

  • 5 genes correlated to 'GENDER'.

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

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • PLAGL2|5326 ,  POFUT1|23509 ,  SLC19A3|80704 ,  SLC5A6|8884 ,  MUC2|4583 ,  ...

  • 30 genes correlated to 'COMPLETENESS_OF_RESECTION'.

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

  • 30 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

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

  • 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 'RADIATIONS_RADIATION_REGIMENINDICATION'.

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=14 younger N=16
PRIMARY_SITE_OF_DISEASE Wilcoxon test N=30 rectum N=30 colon N=0
NEOPLASM_DISEASESTAGE 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=10 lower stage N=20
PATHOLOGY_M_STAGE Wilcoxon test N=30 class1 N=30 class0 N=0
GENDER Wilcoxon test N=5 male N=5 female N=0
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
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=11 lower number_of_lymph_nodes N=19
RACE Kruskal-Wallis test N=30        
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) 0-140.4 (median=19.3)
  censored N = 500
  death N = 115
     
  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) 66.36 (13)
  Significant markers N = 30
  pos. correlated 14
  neg. correlated 16
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 -0.2414 1.491e-09 2.69e-05
MGA|23269 -0.2342 4.28e-09 3.86e-05
AMH|268 0.2222 4.666e-08 0.000281
CNTD2|79935 0.2049 3.175e-07 0.00109
LOC154761|154761 0.204 3.508e-07 0.00109
MRE11A|4361 -0.2038 3.618e-07 0.00109
ZNF75A|7627 -0.1982 7.709e-07 0.00199
PPP1R10|5514 -0.1934 1.385e-06 0.00277
THADA|63892 -0.1933 1.403e-06 0.00277
TGFBR2|7048 -0.1926 1.534e-06 0.00277
Clinical variable #3: 'PRIMARY_SITE_OF_DISEASE'

30 genes related to 'PRIMARY_SITE_OF_DISEASE'.

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

PRIMARY_SITE_OF_DISEASE Labels N
  COLON 449
  RECTUM 163
     
  Significant markers N = 30
  Higher in RECTUM 30
  Higher in COLON 0
List of top 10 genes differentially expressed by 'PRIMARY_SITE_OF_DISEASE'

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

W(pos if higher in 'RECTUM') wilcoxontestP Q AUC
HOXB13|10481 51537 4.406e-15 7.95e-11 0.7073
ZNF528|84436 48562.5 3.005e-10 2.51e-06 0.6665
HOXC6|3223 16053 4.884e-10 2.51e-06 0.6832
HOXC4|3221 19220.5 5.793e-10 2.51e-06 0.6738
ELAVL2|1993 39613 6.96e-10 2.51e-06 0.6693
ZNF662|389114 47980 1.032e-09 3.1e-06 0.6615
ZNF813|126017 47854 1.554e-09 4e-06 0.6597
ZNF530|348327 47978 2.034e-09 4.59e-06 0.6585
ZNF141|7700 47621 2.353e-09 4.72e-06 0.658
MAP7D2|256714 46404 3.529e-09 6.37e-06 0.657
Clinical variable #4: 'NEOPLASM_DISEASESTAGE'

30 genes related to 'NEOPLASM_DISEASESTAGE'.

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

NEOPLASM_DISEASESTAGE Labels N
  STAGE I 104
  STAGE IA 1
  STAGE II 37
  STAGE IIA 176
  STAGE IIB 11
  STAGE IIC 3
  STAGE III 27
  STAGE IIIA 21
  STAGE IIIB 79
  STAGE IIIC 54
  STAGE IV 60
  STAGE IVA 27
  STAGE IVB 2
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'NEOPLASM_DISEASESTAGE'

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

kruskal_wallis_P Q
RGL2|5863 7.465e-10 1.35e-05
C5ORF23|79614 1.884e-09 1.7e-05
GSR|2936 5.521e-09 3.32e-05
C2CD4A|145741 4.995e-08 0.000214
LAP3|51056 5.935e-08 0.000214
TMEM55A|55529 8.193e-08 0.000229
NPR3|4883 8.874e-08 0.000229
COQ2|27235 1.223e-07 0.000232
PALM2|114299 1.251e-07 0.000232
IRF1|3659 1.376e-07 0.000232
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) 2.87 (0.63)
  N
  T1 20
  T2 107
  T3 419
  T4 68
     
  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 0.2613 5.773e-11 1.04e-06
C5ORF23|79614 0.2519 5.609e-10 5.06e-06
SOX11|6664 0.2404 2.959e-09 1.72e-05
SPP1|6696 0.2349 3.817e-09 1.72e-05
OLR1|4973 0.2338 5.573e-09 1.79e-05
CSRP2|1466 0.2305 7.516e-09 1.79e-05
NALCN|259232 0.245 7.962e-09 1.79e-05
ZFHX4|79776 0.2312 9.036e-09 1.79e-05
HTR2B|3357 0.2347 9.491e-09 1.79e-05
RBP7|116362 0.2296 9.903e-09 1.79e-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 349
  N1 149
  N2 114
     
  Significant markers N = 30
  pos. correlated 10
  neg. correlated 20
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 3.306e-13 5.96e-09
TEAD3|7005 0.2721 7.496e-12 6.76e-08
C5ORF23|79614 0.2684 3.839e-11 2.31e-07
COQ2|27235 -0.2559 1.315e-10 5.93e-07
AGPAT5|55326 -0.2526 2.326e-10 8.39e-07
RGL2|5863 0.2505 3.28e-10 9.49e-07
CASP1|834 -0.2498 3.683e-10 9.49e-07
NPR3|4883 0.2664 6.054e-10 1.37e-06
NAT1|9 -0.2451 8.032e-10 1.61e-06
PBK|55872 -0.2389 2.23e-09 4.02e-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 456
  class1 85
     
  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 10905 1.505e-10 2.71e-06 0.7187
IRF1|3659 11750 8.104e-09 7.31e-05 0.6969
GFI1|2672 12128 4.239e-08 0.000255 0.6871
WARS|7453 12232 6.591e-08 0.000297 0.6844
RARRES3|5920 12426 1.477e-07 0.000385 0.6794
IDO1|3620 12374 1.508e-07 0.000385 0.6793
CIITA|4261 12460 1.698e-07 0.000385 0.6785
C13ORF15|28984 26299 1.705e-07 0.000385 0.6785
TYMS|7298 12585 2.819e-07 0.000565 0.6753
CXCL9|4283 12685 4.201e-07 0.000758 0.6727
Clinical variable #8: 'GENDER'

5 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 288
  MALE 328
     
  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 24276 1.509e-39 3.02e-36 0.9868
CYORF15B|84663 20784 1.766e-34 2.28e-31 0.9808
HDHD1A|8226 22137 4.877e-30 5.5e-27 0.7657
CA5BP|340591 23369 2.548e-27 2.55e-24 0.7526
NCRNA00183|554203 25052 7.977e-24 6.85e-21 0.7348
Clinical variable #9: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  COLON ADENOCARCINOMA 387
  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 S17.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

kruskal_wallis_P Q
PLAGL2|5326 5.175e-21 9.34e-17
POFUT1|23509 6.227e-20 5.62e-16
SLC19A3|80704 1.115e-18 6.71e-15
SLC5A6|8884 1.529e-18 6.9e-15
MUC2|4583 4.2e-18 1.51e-14
SNHG11|128439 5.024e-18 1.51e-14
TAF4|6874 8.835e-18 2.28e-14
KIAA0406|9675 1.025e-17 2.31e-14
HNF4A|3172 1.374e-17 2.75e-14
SPDEF|25803 2.3e-17 4.05e-14
Clinical variable #10: 'RADIATIONS_RADIATION_REGIMENINDICATION'

No gene related to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

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

RADIATIONS_RADIATION_REGIMENINDICATION Labels N
  NO 9
  YES 607
     
  Significant markers N = 0
Clinical variable #11: 'COMPLETENESS_OF_RESECTION'

30 genes related to 'COMPLETENESS_OF_RESECTION'.

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

COMPLETENESS_OF_RESECTION Labels N
  R0 446
  R1 5
  R2 35
  RX 30
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'COMPLETENESS_OF_RESECTION'

Table S20.  Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS_OF_RESECTION'

kruskal_wallis_P Q
LOC150776|150776 4.315e-12 3.84e-08
RRN3P2|653390 6.022e-12 3.84e-08
PMS2CL|441194 6.39e-12 3.84e-08
POLR2J4|84820 1.087e-11 4.9e-08
SPDYE8P|389517 1.975e-11 5.94e-08
PMS2L2|5380 1.975e-11 5.94e-08
GUSBL2|375513 2.538e-11 6.54e-08
STAG3L2|442582 2.964e-11 6.68e-08
NSUN5P1|155400 3.42e-11 6.86e-08
AGAP11|119385 4.21e-11 7.41e-08
Clinical variable #12: 'NUMBER_OF_LYMPH_NODES'

30 genes related to 'NUMBER_OF_LYMPH_NODES'.

Table S21.  Basic characteristics of clinical feature: 'NUMBER_OF_LYMPH_NODES'

NUMBER_OF_LYMPH_NODES Mean (SD) 2.22 (4.7)
  Significant markers N = 30
  pos. correlated 11
  neg. correlated 19
List of top 10 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

Table S22.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER_OF_LYMPH_NODES' by Spearman correlation test

SpearmanCorr corrP Q
GSR|2936 -0.285 2.679e-12 4.83e-08
C5ORF23|79614 0.2707 8.87e-11 8e-07
TEAD3|7005 0.2583 2.703e-10 1.41e-06
CASP1|834 -0.2574 3.124e-10 1.41e-06
NPR3|4883 0.2754 4.555e-10 1.64e-06
COQ2|27235 -0.2489 1.223e-09 3.68e-06
CXCL2|2920 -0.2464 1.794e-09 4.62e-06
AGPAT5|55326 -0.2452 2.17e-09 4.89e-06
MINPP1|9562 -0.2428 3.147e-09 6.31e-06
RGL2|5863 0.2412 4.027e-09 7.27e-06
Clinical variable #13: 'RACE'

30 genes related to 'RACE'.

Table S23.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 12
  BLACK OR AFRICAN AMERICAN 60
  WHITE 294
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S24.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
C14ORF167|55449 1.961e-13 3.54e-09
ULK4|54986 4.543e-13 4.1e-09
CROCCL1|84809 3.514e-12 2.11e-08
PPIL3|53938 4.431e-11 2e-07
NOTCH2NL|388677 2.106e-10 7.6e-07
SPDYE1|285955 5.892e-10 1.77e-06
RPS26|6231 1.304e-09 3.14e-06
LOC441455|441455 1.394e-09 3.14e-06
SPDYE6|729597 4.674e-09 9.34e-06
POLR2J3|548644 5.175e-09 9.34e-06
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 = 616

  • Number of genes = 18041

  • Number of clinical features = 13

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)