Correlation between mRNAseq expression and clinical features
Colon Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C1J101WF
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1J101WF
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 18006 genes and 12 clinical features across 430 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one genes.

  • 15 genes correlated to 'AGE'.

    • MTERF|7978 ,  AMH|268 ,  MGA|23269 ,  ZNF75A|7627 ,  DNM3|26052 ,  ...

  • 24 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • RGL2|5863 ,  C5ORF23|79614 ,  TEAD3|7005 ,  C2CD4A|145741 ,  C13ORF15|28984 ,  ...

  • 17 genes correlated to 'PATHOLOGY.T.STAGE'.

    • TCHH|7062 ,  C10ORF114|399726 ,  CSRP2|1466 ,  RIMKLB|57494 ,  GJB2|2706 ,  ...

  • 179 genes correlated to 'PATHOLOGY.N.STAGE'.

    • TEAD3|7005 ,  AGPAT5|55326 ,  NAT1|9 ,  RGL2|5863 ,  GSR|2936 ,  ...

  • 153 genes correlated to 'PATHOLOGY.M.STAGE'.

    • NBPF15|284565 ,  PPIAL4D|645142 ,  FUNDC2P2|388965 ,  LAP3|51056 ,  POTEE|445582 ,  ...

  • 7 genes correlated to 'GENDER'.

    • CYORF15A|246126 ,  CYORF15B|84663 ,  HDHD1A|8226 ,  NCRNA00183|554203 ,  C2ORF84|653140 ,  ...

  • 843 genes correlated to 'HISTOLOGICAL.TYPE'.

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

  • 361 genes correlated to 'COMPLETENESS.OF.RESECTION'.

    • RRN3P2|653390 ,  NSUN5P1|155400 ,  LOC100132287|100132287 ,  LOC100133331|100133331 ,  LOC150776|150776 ,  ...

  • 108 genes correlated to 'NUMBER.OF.LYMPH.NODES'.

    • NPR3|4883 ,  RGL2|5863 ,  TEAD3|7005 ,  CASP1|834 ,  C5ORF23|79614 ,  ...

  • 10 genes correlated to 'RACE'.

    • LOC441455|441455 ,  ULK4|54986 ,  C14ORF167|55449 ,  NOTCH2NL|388677 ,  LOC90784|90784 ,  ...

  • No genes correlated to 'Time to Death', 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
Time to Death Cox regression test   N=0        
AGE Spearman correlation test N=15 older N=11 younger N=4
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=24        
PATHOLOGY T STAGE Spearman correlation test N=17 higher stage N=17 lower stage N=0
PATHOLOGY N STAGE Spearman correlation test N=179 higher stage N=108 lower stage N=71
PATHOLOGY M STAGE Kruskal-Wallis test N=153        
GENDER Wilcoxon test N=7 male N=7 female N=0
HISTOLOGICAL TYPE Wilcoxon test N=843 colon mucinous adenocarcinoma N=843 colon adenocarcinoma N=0
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test   N=0        
COMPLETENESS OF RESECTION Kruskal-Wallis test N=361        
NUMBER OF LYMPH NODES Spearman correlation test N=108 higher number.of.lymph.nodes N=61 lower number.of.lymph.nodes N=47
RACE Kruskal-Wallis test N=10        
Clinical variable #1: 'Time to Death'

No gene related to 'Time to Death'.

Table S1.  Basic characteristics of clinical feature: 'Time to Death'

Time to Death Duration (Months) 0.1-140.4 (median=20.3)
  censored N = 328
  death N = 85
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

15 genes related to 'AGE'.

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

AGE Mean (SD) 67.17 (13)
  Significant markers N = 15
  pos. correlated 11
  neg. correlated 4
List of top 10 genes differentially expressed by 'AGE'

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

SpearmanCorr corrP Q
MTERF|7978 -0.2702 1.457e-08 0.000262
AMH|268 0.2637 4.986e-08 0.000898
MGA|23269 -0.2391 5.445e-07 0.0098
ZNF75A|7627 -0.2331 1.115e-06 0.0201
DNM3|26052 -0.2241 2.748e-06 0.0495
FOXD4L1|200350 0.2263 3.48e-06 0.0626
AGAP7|653268 0.2183 5.142e-06 0.0926
CNTD2|79935 0.2167 6.218e-06 0.112
FGF8|2253 0.2816 7.271e-06 0.131
HOXD4|3233 0.2181 7.898e-06 0.142
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

24 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S4.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 71
  STAGE IA 1
  STAGE II 27
  STAGE IIA 130
  STAGE IIB 9
  STAGE IIC 1
  STAGE III 21
  STAGE IIIA 13
  STAGE IIIB 53
  STAGE IIIC 36
  STAGE IV 42
  STAGE IVA 16
  STAGE IVB 1
     
  Significant markers N = 24
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'

ANOVA_P Q
RGL2|5863 1.189e-08 0.000214
C5ORF23|79614 1.662e-07 0.00299
TEAD3|7005 1.317e-06 0.0237
C2CD4A|145741 1.458e-06 0.0263
C13ORF15|28984 1.938e-06 0.0349
NPR3|4883 2.335e-06 0.042
PALM2|114299 3.125e-06 0.0563
HOXA4|3201 3.366e-06 0.0606
IRF1|3659 3.584e-06 0.0645
GFI1|2672 3.656e-06 0.0658
Clinical variable #4: 'PATHOLOGY.T.STAGE'

17 genes related to 'PATHOLOGY.T.STAGE'.

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.89 (0.63)
  N
  0 1
  1 10
  2 75
  3 294
  4 49
     
  Significant markers N = 17
  pos. correlated 17
  neg. correlated 0
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
TCHH|7062 0.2509 3.337e-07 0.00601
C10ORF114|399726 0.2438 4.217e-07 0.00759
CSRP2|1466 0.2383 5.94e-07 0.0107
RIMKLB|57494 0.2317 1.223e-06 0.022
GJB2|2706 0.2285 1.733e-06 0.0312
SOX11|6664 0.23 2.18e-06 0.0392
HTR2B|3357 0.2316 2.337e-06 0.0421
C11ORF41|25758 0.2189 5.245e-06 0.0944
CAMK2B|816 0.2278 8.838e-06 0.159
C5ORF23|79614 0.2167 8.852e-06 0.159
Clinical variable #5: 'PATHOLOGY.N.STAGE'

179 genes related to 'PATHOLOGY.N.STAGE'.

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.58 (0.77)
  N
  0 254
  1 101
  2 74
     
  Significant markers N = 179
  pos. correlated 108
  neg. correlated 71
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
TEAD3|7005 0.2995 2.431e-10 4.38e-06
AGPAT5|55326 -0.2963 3.837e-10 6.91e-06
NAT1|9 -0.2956 4.258e-10 7.67e-06
RGL2|5863 0.2895 9.893e-10 1.78e-05
GSR|2936 -0.2887 1.119e-09 2.01e-05
NPR3|4883 0.3049 2.352e-09 4.23e-05
PDE12|201626 -0.2789 4.191e-09 7.54e-05
PBK|55872 -0.275 7.234e-09 0.00013
C5ORF23|79614 0.2759 1.197e-08 0.000215
TCHH|7062 0.2784 1.319e-08 0.000237
Clinical variable #6: 'PATHOLOGY.M.STAGE'

153 genes related to 'PATHOLOGY.M.STAGE'.

Table S10.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 323
  M1 50
  M1A 7
  M1B 1
  MX 42
     
  Significant markers N = 153
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'

ANOVA_P Q
NBPF15|284565 3.353e-09 6.04e-05
PPIAL4D|645142 1.427e-08 0.000257
FUNDC2P2|388965 2.369e-08 0.000426
LAP3|51056 3.084e-08 0.000555
POTEE|445582 3.42e-08 0.000616
NCRNA00182|100302692 5.575e-08 0.001
LOC728989|728989 8.755e-08 0.00158
C14ORF19|280655 1.021e-07 0.00184
UBE2NL|389898 1.037e-07 0.00187
LOC90586|90586 1.356e-07 0.00244
Clinical variable #7: 'GENDER'

7 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 202
  MALE 228
     
  Significant markers N = 7
  Higher in MALE 7
  Higher in FEMALE 0
List of 7 genes differentially expressed by 'GENDER'

Table S13.  Get Full Table List of 7 genes differentially expressed by 'GENDER'. 37 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
CYORF15A|246126 12214 2.548e-29 4.59e-25 0.992
CYORF15B|84663 9541 1.355e-23 2.44e-19 0.9818
HDHD1A|8226 10610 4.691e-22 8.44e-18 0.7696
NCRNA00183|554203 12683 8.766e-16 1.58e-11 0.7246
C2ORF84|653140 14994 3.407e-06 0.0612 0.6553
FRG1B|284802 28728.5 5.707e-06 0.103 0.6269
ZNF578|147660 17190.5 1.496e-05 0.269 0.6214
Clinical variable #8: 'HISTOLOGICAL.TYPE'

843 genes related to 'HISTOLOGICAL.TYPE'.

Table S14.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  COLON ADENOCARCINOMA 372
  COLON MUCINOUS ADENOCARCINOMA 56
     
  Significant markers N = 843
  Higher in COLON MUCINOUS ADENOCARCINOMA 843
  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
MUC2|4583 16977 2.914e-14 5.25e-10 0.8149
SLC19A3|80704 3859.5 3.033e-14 5.46e-10 0.8147
PLAGL2|5326 3909 4.717e-14 8.49e-10 0.8124
UQCC|55245 4184 5.166e-13 9.3e-09 0.7992
SLC5A6|8884 4282 1.183e-12 2.13e-08 0.7945
CREB3L1|90993 16507 1.696e-12 3.05e-08 0.7924
ACSL5|51703 4369 2.444e-12 4.4e-08 0.7903
AQP3|360 16447 2.789e-12 5.02e-08 0.7895
TOMM34|10953 4404 3.262e-12 5.87e-08 0.7886
POFUT1|23509 4418 3.66e-12 6.59e-08 0.7879
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 427
     
  Significant markers N = 0
Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

361 genes related to 'COMPLETENESS.OF.RESECTION'.

Table S17.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 305
  R1 3
  R2 23
  RX 24
     
  Significant markers N = 361
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'

ANOVA_P Q
RRN3P2|653390 6.951e-10 1.25e-05
NSUN5P1|155400 7.889e-10 1.42e-05
LOC100132287|100132287 8.067e-10 1.45e-05
LOC100133331|100133331 1.112e-09 2e-05
LOC150776|150776 1.124e-09 2.02e-05
SPDYE8P|389517 1.462e-09 2.63e-05
PMS2L2|5380 2.276e-09 4.1e-05
LOC339047|339047 2.351e-09 4.23e-05
PMS2CL|441194 2.468e-09 4.44e-05
LOC728875|728875 2.557e-09 4.6e-05
Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

108 genes related to 'NUMBER.OF.LYMPH.NODES'.

Table S19.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.01 (4.4)
  Significant markers N = 108
  pos. correlated 61
  neg. correlated 47
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 0.3219 8.798e-10 1.58e-05
RGL2|5863 0.2927 1.842e-09 3.32e-05
TEAD3|7005 0.2891 2.947e-09 5.31e-05
CASP1|834 -0.2829 6.54e-09 0.000118
C5ORF23|79614 0.2881 6.826e-09 0.000123
MINPP1|9562 -0.2798 9.785e-09 0.000176
GSR|2936 -0.2797 9.868e-09 0.000178
AGPAT5|55326 -0.2785 1.14e-08 0.000205
PALM2|114299 0.2736 2.889e-08 0.00052
NAT1|9 -0.2709 2.93e-08 0.000527
Clinical variable #12: 'RACE'

10 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 36
  WHITE 213
     
  Significant markers N = 10
List of 10 genes differentially expressed by 'RACE'

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

ANOVA_P Q
LOC441455|441455 2.856e-10 5.14e-06
ULK4|54986 4.744e-09 8.54e-05
C14ORF167|55449 3.545e-08 0.000638
NOTCH2NL|388677 7.033e-08 0.00127
LOC90784|90784 2.232e-06 0.0402
TMEM232|642987 2.948e-06 0.0531
CYP3A5|1577 4.688e-06 0.0844
ACSM1|116285 4.702e-06 0.0846
CROCCL1|84809 5.483e-06 0.0987
CRYBB2|1415 8.834e-06 0.159
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 = 430

  • Number of genes = 18006

  • Number of clinical features = 12

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

ANOVA analysis

For multi-class clinical features (ordinal or nominal), one-way analysis of variance (Howell 2002) was applied to compare the log2-expression levels between different clinical classes using 'anova' function in R

Student's t-test analysis

For two-class clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the log2-expression levels between the two clinical classes using 't.test' function in R

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] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[4] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[5] 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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