Correlation between mRNAseq expression and clinical features
Colon Adenocarcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1DB80T1
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/C1DB80T1
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 18012 genes and 12 clinical features across 450 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • MTERF|7978 ,  MGA|23269 ,  AMH|268 ,  DNM3|26052 ,  PPP1R10|5514 ,  ...

  • 30 genes correlated to 'NEOPLASM_DISEASESTAGE'.

    • RGL2|5863 ,  C5ORF23|79614 ,  GFI1|2672 ,  TEAD3|7005 ,  AGPAT5|55326 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • RIMKLB|57494 ,  C10ORF114|399726 ,  TCHH|7062 ,  SOX11|6664 ,  C5ORF23|79614 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • AGPAT5|55326 ,  GSR|2936 ,  NAT1|9 ,  PDE12|201626 ,  PBK|55872 ,  ...

  • 30 genes correlated to 'PATHOLOGY_M_STAGE'.

    • LAP3|51056 ,  IRF1|3659 ,  TYMS|7298 ,  GFI1|2672 ,  CXCL9|4283 ,  ...

  • 5 genes correlated to 'GENDER'.

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

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • PLAGL2|5326 ,  SLC19A3|80704 ,  MUC2|4583 ,  SLC5A6|8884 ,  UQCC|55245 ,  ...

  • 30 genes correlated to 'COMPLETENESS_OF_RESECTION'.

    • LOC150776|150776 ,  NSUN5P1|155400 ,  SPDYE8P|389517 ,  LOC100133331|100133331 ,  LOC100132287|100132287 ,  ...

  • 30 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

    • NPR3|4883 ,  GSR|2936 ,  AGPAT5|55326 ,  RGL2|5863 ,  TEAD3|7005 ,  ...

  • 30 genes correlated to 'RACE'.

    • ULK4|54986 ,  CROCCL1|84809 ,  C14ORF167|55449 ,  LOC441455|441455 ,  SPDYE1|285955 ,  ...

  • 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=20 younger N=10
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=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
HISTOLOGICAL_TYPE Wilcoxon test N=30 colon mucinous adenocarcinoma N=30 colon adenocarcinoma N=0
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=8 lower number_of_lymph_nodes N=22
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=21)
  censored N = 355
  death N = 94
     
  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) 66.99 (13)
  Significant markers N = 30
  pos. correlated 20
  neg. correlated 10
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 -0.2662 1.183e-08 0.000213
MGA|23269 -0.2415 2.297e-07 0.00207
AMH|268 0.2367 6.688e-07 0.004
DNM3|26052 -0.2297 8.881e-07 0.004
PPP1R10|5514 -0.2238 1.709e-06 0.00521
ZNF75A|7627 -0.2242 1.736e-06 0.00521
FGF8|2253 0.288 2.328e-06 0.00599
LOC154761|154761 0.219 2.946e-06 0.00663
AGAP7|653268 0.2117 6.375e-06 0.0107
CNTD2|79935 0.2115 6.657e-06 0.0107
Clinical variable #3: 'NEOPLASM_DISEASESTAGE'

30 genes related to 'NEOPLASM_DISEASESTAGE'.

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

NEOPLASM_DISEASESTAGE Labels N
  STAGE I 74
  STAGE IA 1
  STAGE II 29
  STAGE IIA 136
  STAGE IIB 9
  STAGE IIC 1
  STAGE III 21
  STAGE IIIA 12
  STAGE IIIB 56
  STAGE IIIC 39
  STAGE IV 43
  STAGE IVA 18
  STAGE IVB 2
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'NEOPLASM_DISEASESTAGE'

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

kruskal_wallis_P Q
RGL2|5863 2.025e-09 3.65e-05
C5ORF23|79614 1.524e-07 0.00116
GFI1|2672 1.937e-07 0.00116
TEAD3|7005 3.112e-07 0.0014
AGPAT5|55326 4.956e-07 0.00179
GSR|2936 6.269e-07 0.00188
PALM2|114299 8.175e-07 0.0021
PBK|55872 1.279e-06 0.00253
NPR3|4883 1.405e-06 0.00253
MINPP1|9562 1.62e-06 0.00253
Clinical variable #4: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

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

PATHOLOGY_T_STAGE Mean (SD) 2.9 (0.62)
  N
  T1 11
  T2 78
  T3 306
  T4 54
     
  Significant markers N = 30
  pos. correlated 29
  neg. correlated 1
List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S7.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
RIMKLB|57494 0.2286 9.827e-07 0.00454
C10ORF114|399726 0.2294 1.19e-06 0.00454
TCHH|7062 0.233 1.266e-06 0.00454
SOX11|6664 0.2296 1.331e-06 0.00454
C5ORF23|79614 0.2267 1.874e-06 0.00454
FSTL3|10272 0.2227 1.884e-06 0.00454
HTR2B|3357 0.2279 1.952e-06 0.00454
CSRP2|1466 0.2221 2.015e-06 0.00454
C11ORF41|25758 0.2213 2.422e-06 0.00485
GJB2|2706 0.213 5.305e-06 0.00879
Clinical variable #5: 'PATHOLOGY_N_STAGE'

30 genes related to 'PATHOLOGY_N_STAGE'.

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

PATHOLOGY_N_STAGE Mean (SD) 0.59 (0.78)
  N
  N0 264
  N1 104
  N2 81
     
  Significant markers N = 30
  pos. correlated 11
  neg. correlated 19
List of top 10 genes differentially expressed by 'PATHOLOGY_N_STAGE'

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

SpearmanCorr corrP Q
AGPAT5|55326 -0.3081 2.498e-11 2.75e-07
GSR|2936 -0.3068 3.052e-11 2.75e-07
NAT1|9 -0.3003 8.29e-11 4.98e-07
PDE12|201626 -0.2944 1.987e-10 8.66e-07
PBK|55872 -0.2934 2.404e-10 8.66e-07
TEAD3|7005 0.291 3.245e-10 9.74e-07
NPR3|4883 0.3088 5.932e-10 1.53e-06
RGL2|5863 0.284 8.88e-10 2e-06
INTS10|55174 -0.2821 1.16e-09 2.32e-06
CDCA2|157313 -0.2789 1.911e-09 3.15e-06
Clinical variable #6: 'PATHOLOGY_M_STAGE'

30 genes related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 329
  class1 62
     
  Significant markers N = 30
  Higher in class1 30
  Higher in class0 0
List of top 10 genes differentially expressed by 'PATHOLOGY_M_STAGE'

Table S11.  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 4919 9.954e-11 1.79e-06 0.7588
IRF1|3659 5721 4.131e-08 0.000372 0.7195
TYMS|7298 5812 7.715e-08 0.000463 0.7151
GFI1|2672 5943 1.856e-07 0.000794 0.7086
CXCL9|4283 5969 2.203e-07 0.000794 0.7074
CXCR6|10663 6021 3.508e-07 0.000917 0.7039
RASGRP1|10125 6004 3.562e-07 0.000917 0.7039
HOXA4|3201 14238 4.382e-07 0.000932 0.7023
C13ORF15|28984 14309 4.795e-07 0.000932 0.7015
WARS|7453 6101 5.177e-07 0.000932 0.7009
Clinical variable #7: 'GENDER'

5 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 213
  MALE 237
     
  Significant markers N = 5
  Higher in MALE 5
  Higher in FEMALE 0
List of 5 genes differentially expressed by 'GENDER'

Table S13.  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 13156 2.858e-30 5.15e-27 0.9913
CYORF15B|84663 10386 1.251e-24 1.5e-21 0.9821
CA5BP|340591 11648 5.739e-23 6.46e-20 0.7693
HDHD1A|8226 11964 5.503e-22 5.83e-19 0.763
NCRNA00183|554203 13754 7.5e-17 6.14e-14 0.7275
Clinical variable #8: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  COLON ADENOCARCINOMA 387
  COLON MUCINOUS ADENOCARCINOMA 61
     
  Significant markers N = 30
  Higher in COLON MUCINOUS ADENOCARCINOMA 30
  Higher in COLON ADENOCARCINOMA 0
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S15.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

W(pos if higher in 'COLON MUCINOUS ADENOCARCINOMA') wilcoxontestP Q AUC
PLAGL2|5326 4417 3.878e-15 4.24e-11 0.8129
SLC19A3|80704 4486.5 6.979e-15 4.24e-11 0.81
MUC2|4583 19119 7.068e-15 4.24e-11 0.8099
SLC5A6|8884 4786 8.256e-14 3.37e-10 0.7973
UQCC|55245 4811 1.01e-13 3.37e-10 0.7962
CREB3L1|90993 18783 1.121e-13 3.37e-10 0.7957
POFUT1|23509 4954 3.159e-13 7.34e-10 0.7901
ACSL5|51703 4958 3.261e-13 7.34e-10 0.79
TOMM34|10953 5043 6.351e-13 1.27e-09 0.7864
AQP3|360 18535 7.958e-13 1.43e-09 0.7851
Clinical variable #9: 'RADIATIONS_RADIATION_REGIMENINDICATION'

No gene related to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

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

RADIATIONS_RADIATION_REGIMENINDICATION Labels N
  NO 3
  YES 447
     
  Significant markers N = 0
Clinical variable #10: 'COMPLETENESS_OF_RESECTION'

30 genes related to 'COMPLETENESS_OF_RESECTION'.

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

COMPLETENESS_OF_RESECTION Labels N
  R0 323
  R1 3
  R2 23
  RX 25
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'COMPLETENESS_OF_RESECTION'

Table S18.  Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS_OF_RESECTION'

kruskal_wallis_P Q
LOC150776|150776 1.579e-10 1e-06
NSUN5P1|155400 1.952e-10 1e-06
SPDYE8P|389517 2.497e-10 1e-06
LOC100133331|100133331 2.708e-10 1e-06
LOC100132287|100132287 2.783e-10 1e-06
RRN3P2|653390 3.694e-10 1.11e-06
LOC339047|339047 4.999e-10 1.29e-06
PMS2L2|5380 6.257e-10 1.41e-06
POLR2J4|84820 8.269e-10 1.65e-06
PMS2CL|441194 1.09e-09 1.96e-06
Clinical variable #11: 'NUMBER_OF_LYMPH_NODES'

30 genes related to 'NUMBER_OF_LYMPH_NODES'.

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

NUMBER_OF_LYMPH_NODES Mean (SD) 2.05 (4.4)
  Significant markers N = 30
  pos. correlated 8
  neg. correlated 22
List of top 10 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

Table S20.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER_OF_LYMPH_NODES' by Spearman correlation test

SpearmanCorr corrP Q
NPR3|4883 0.3235 2.746e-10 2.49e-06
GSR|2936 -0.2999 2.769e-10 2.49e-06
AGPAT5|55326 -0.2935 6.856e-10 4.12e-06
RGL2|5863 0.289 1.275e-09 5.74e-06
TEAD3|7005 0.2839 2.53e-09 7.77e-06
MINPP1|9562 -0.2829 2.921e-09 7.77e-06
NAT1|9 -0.2826 3.02e-09 7.77e-06
C5ORF23|79614 0.2856 4.085e-09 9.2e-06
PBK|55872 -0.2751 8.471e-09 1.7e-05
CASP1|834 -0.2727 1.099e-08 1.98e-05
Clinical variable #12: 'RACE'

30 genes related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 11
  BLACK OR AFRICAN AMERICAN 54
  WHITE 213
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S22.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
ULK4|54986 1.338e-11 1.58e-07
CROCCL1|84809 1.944e-11 1.58e-07
C14ORF167|55449 2.63e-11 1.58e-07
LOC441455|441455 1.586e-10 7.14e-07
SPDYE1|285955 2.899e-09 1.04e-05
CYP3A5|1577 8.959e-09 2.62e-05
SPDYE6|729597 1.019e-08 2.62e-05
NOTCH2NL|388677 2.023e-08 4.09e-05
PPIL3|53938 2.043e-08 4.09e-05
SPDYE5|442590 3.139e-08 5.65e-05
Methods & Data
Input

  • Expresson data file = COAD-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt

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

  • Number of patients = 450

  • Number of genes = 18012

  • Number of clinical features = 12

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)
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