Correlation between mRNAseq expression and clinical features
Colon Adenocarcinoma (Primary solid tumor)
16 April 2014  |  analyses__2014_04_16
Maintainer Information
Citation Information
doi:10.7908/C1NZ8678
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/C1NZ8678
Overview
Introduction

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

Summary

Testing the association between 18006 genes and 11 clinical features across 430 samples, statistically thresholded by Q value < 0.05, 10 clinical features related to at least one genes.

  • 5 genes correlated to 'AGE'.

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

  • 33 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • ZNF845|91664 ,  TEAD3|7005 ,  SCN5A|6331 ,  RGL2|5863 ,  PRSS8|5652 ,  ...

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

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

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

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

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

    • OR6W1P|89883 ,  NBPF15|284565 ,  FUNDC2P2|388965 ,  LOC728554|728554 ,  PPIAL4D|645142 ,  ...

  • 37 genes correlated to 'GENDER'.

    • XIST|7503 ,  ZFY|7544 ,  RPS4Y1|6192 ,  DDX3Y|8653 ,  KDM5D|8284 ,  ...

  • 443 genes correlated to 'HISTOLOGICAL.TYPE'.

    • PLAGL2|5326 ,  POFUT1|23509 ,  SDR16C5|195814 ,  SLC5A6|8884 ,  MUC2|4583 ,  ...

  • 77 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • DFNB31|25861 ,  SKP2|6502 ,  PLSCR4|57088 ,  CDK19|23097 ,  AMPH|273 ,  ...

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

    • LOC728875|728875 ,  NSUN5P1|155400 ,  LOC150776|150776 ,  RRN3P2|653390 ,  AGAP11|119385 ,  ...

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

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

  • No genes correlated to 'Time to Death'

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 Q value < 0.05.

Clinical feature Statistical test Significant genes Associated with                 Associated with
Time to Death Cox regression test   N=0        
AGE Spearman correlation test N=5 older N=1 younger N=4
NEOPLASM DISEASESTAGE ANOVA test N=33        
PATHOLOGY T STAGE Spearman correlation test N=7 higher stage N=7 lower stage N=0
PATHOLOGY N STAGE Spearman correlation test N=71 higher stage N=36 lower stage N=35
PATHOLOGY M STAGE ANOVA test N=100        
GENDER t test N=37 male N=15 female N=22
HISTOLOGICAL TYPE t test N=443 colon mucinous adenocarcinoma N=231 colon adenocarcinoma N=212
RADIATIONS RADIATION REGIMENINDICATION t test N=77 yes N=36 no N=41
COMPLETENESS OF RESECTION ANOVA test N=234        
NUMBER OF LYMPH NODES Spearman correlation test N=49 higher number.of.lymph.nodes N=22 lower number.of.lymph.nodes N=27
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=17)
  censored N = 309
  death N = 82
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

5 genes related to 'AGE'.

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

AGE Mean (SD) 67.17 (13)
  Significant markers N = 5
  pos. correlated 1
  neg. correlated 4
List of 5 genes significantly correlated to 'AGE' by Spearman correlation test

Table S3.  Get Full Table List of 5 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

Figure S1.  Get High-res Image As an example, this figure shows the association of MTERF|7978 to 'AGE'. P value = 1.46e-08 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

33 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 32
  STAGE IIA 125
  STAGE IIB 9
  STAGE IIC 1
  STAGE III 22
  STAGE IIIA 13
  STAGE IIIB 52
  STAGE IIIC 36
  STAGE IV 42
  STAGE IVA 16
  STAGE IVB 1
     
  Significant markers N = 33
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
ZNF845|91664 1.445e-09 2.6e-05
TEAD3|7005 9.687e-09 0.000174
SCN5A|6331 1.216e-08 0.000219
RGL2|5863 2.173e-08 0.000391
PRSS8|5652 2.427e-08 0.000437
PRH1|5554 7.191e-08 0.00129
C5ORF23|79614 9.13e-08 0.00164
PALM2|114299 9.761e-08 0.00176
C13ORF15|28984 1e-07 0.0018
MACC1|346389 2.011e-07 0.00362

Figure S2.  Get High-res Image As an example, this figure shows the association of ZNF845|91664 to 'NEOPLASM.DISEASESTAGE'. P value = 1.44e-09 with ANOVA analysis.

Clinical variable #4: 'PATHOLOGY.T.STAGE'

7 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 = 7
  pos. correlated 7
  neg. correlated 0
List of 7 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

Table S7.  Get Full Table List of 7 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

Figure S3.  Get High-res Image As an example, this figure shows the association of TCHH|7062 to 'PATHOLOGY.T.STAGE'. P value = 3.34e-07 with Spearman correlation analysis.

Clinical variable #5: 'PATHOLOGY.N.STAGE'

71 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 = 71
  pos. correlated 36
  neg. correlated 35
List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

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

Figure S4.  Get High-res Image As an example, this figure shows the association of TEAD3|7005 to 'PATHOLOGY.N.STAGE'. P value = 2.43e-10 with Spearman correlation analysis.

Clinical variable #6: 'PATHOLOGY.M.STAGE'

100 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 = 100
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
OR6W1P|89883 1.802e-11 3.24e-07
NBPF15|284565 1.612e-10 2.9e-06
FUNDC2P2|388965 7.256e-09 0.000131
LOC728554|728554 1.305e-08 0.000235
PPIAL4D|645142 1.616e-08 0.000291
C2ORF27B|408029 2.221e-08 4e-04
LOC728989|728989 2.226e-08 0.000401
POTEE|445582 2.235e-08 0.000402
FAM171A1|221061 2.71e-08 0.000488
C14ORF19|280655 2.986e-08 0.000537

Figure S5.  Get High-res Image As an example, this figure shows the association of OR6W1P|89883 to 'PATHOLOGY.M.STAGE'. P value = 1.8e-11 with ANOVA analysis.

Clinical variable #7: 'GENDER'

37 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 202
  MALE 228
     
  Significant markers N = 37
  Higher in MALE 15
  Higher in FEMALE 22
List of top 10 genes differentially expressed by 'GENDER'

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

T(pos if higher in 'MALE') ttestP Q AUC
XIST|7503 -43.51 2.777e-141 5e-137 0.9966
ZFY|7544 45.85 3.308e-118 5.96e-114 0.9963
RPS4Y1|6192 38.32 2.751e-114 4.95e-110 0.9967
DDX3Y|8653 43.06 3.773e-85 6.79e-81 0.9979
KDM5D|8284 41.12 4.824e-77 8.68e-73 0.998
TSIX|9383 -21.67 2.268e-64 4.08e-60 0.9607
PRKY|5616 21.51 3.343e-62 6.02e-58 0.9423
NLGN4Y|22829 25.04 2.224e-55 4e-51 0.9825
CYORF15A|246126 30.1 8.603e-53 1.55e-48 0.992
EIF1AY|9086 29.64 2.09e-45 3.76e-41 0.9941

Figure S6.  Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 2.78e-141 with T-test analysis.

Clinical variable #8: 'HISTOLOGICAL.TYPE'

443 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 = 443
  Higher in COLON MUCINOUS ADENOCARCINOMA 231
  Higher in COLON ADENOCARCINOMA 212
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'

T(pos if higher in 'COLON MUCINOUS ADENOCARCINOMA') ttestP Q AUC
PLAGL2|5326 -9.46 8.872e-15 1.6e-10 0.8124
POFUT1|23509 -9.13 2.169e-14 3.9e-10 0.7879
SDR16C5|195814 8.79 4.125e-14 7.43e-10 0.7737
SLC5A6|8884 -9.01 5.432e-14 9.78e-10 0.7945
MUC2|4583 8.68 1.886e-13 3.39e-09 0.8149
UQCC|55245 -8.62 4.001e-13 7.2e-09 0.7992
CREB3L1|90993 8.51 7.582e-13 1.36e-08 0.7924
OSR2|116039 7.96 2.109e-12 3.8e-08 0.7322
AGR3|155465 7.97 2.257e-12 4.06e-08 0.7476
TRPC4AP|26133 -8.02 3.697e-12 6.65e-08 0.7581

Figure S7.  Get High-res Image As an example, this figure shows the association of PLAGL2|5326 to 'HISTOLOGICAL.TYPE'. P value = 8.87e-15 with T-test analysis.

Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

77 genes 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 = 77
  Higher in YES 36
  Higher in NO 41
List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S17.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
DFNB31|25861 -16.77 6.971e-49 1.14e-44 0.7916
SKP2|6502 18.72 6.66e-40 1.09e-35 0.8556
PLSCR4|57088 -12.58 4.723e-30 7.71e-26 0.7169
CDK19|23097 -17.96 4.18e-28 6.82e-24 0.854
AMPH|273 -11.85 6.904e-26 1.13e-21 0.7421
LRRFIP2|9209 -15.88 1.869e-24 3.05e-20 0.8478
COMMD4|54939 16.89 2.401e-24 3.92e-20 0.8384
DNASE2|1777 -11.47 2.572e-24 4.2e-20 0.7322
PIGF|5281 10.85 3.218e-23 5.25e-19 0.7393
FAM24B|196792 -11.86 4.898e-23 7.99e-19 0.7453

Figure S8.  Get High-res Image As an example, this figure shows the association of DFNB31|25861 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 6.97e-49 with T-test analysis.

Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

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

Table S18.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 303
  R1 3
  R2 23
  RX 24
     
  Significant markers N = 234
List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S19.  Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
LOC728875|728875 8.387e-11 1.51e-06
NSUN5P1|155400 1.47e-10 2.65e-06
LOC150776|150776 1.612e-10 2.9e-06
RRN3P2|653390 2.369e-10 4.26e-06
AGAP11|119385 2.675e-10 4.82e-06
LOC100132287|100132287 2.933e-10 5.28e-06
LOC100133331|100133331 3.99e-10 7.18e-06
PMS2L2|5380 4.109e-10 7.4e-06
PMS2CL|441194 7.87e-10 1.42e-05
POLR2J4|84820 1.321e-09 2.38e-05

Figure S9.  Get High-res Image As an example, this figure shows the association of LOC728875|728875 to 'COMPLETENESS.OF.RESECTION'. P value = 8.39e-11 with ANOVA analysis.

Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

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

Table S20.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.01 (4.4)
  Significant markers N = 49
  pos. correlated 22
  neg. correlated 27
List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

Table S21.  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

Figure S10.  Get High-res Image As an example, this figure shows the association of NPR3|4883 to 'NUMBER.OF.LYMPH.NODES'. P value = 8.8e-10 with Spearman correlation analysis. The straight line presents the best linear regression.

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 = 11

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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