Correlation between mRNAseq expression and clinical features
Colon Adenocarcinoma (Primary solid tumor)
15 January 2014  |  analyses__2014_01_15
Maintainer Information
Citation Information
doi:10.7908/C1Z036K0
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/C1Z036K0
Overview
Introduction

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

Summary

Testing the association between 17999 genes and 11 clinical features across 415 samples, statistically thresholded by Q value < 0.05, 10 clinical features related to at least one genes.

  • 4 genes correlated to 'AGE'.

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

  • 25 genes correlated to 'NEOPLASM.DISEASESTAGE'.

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

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

    • C10ORF114|399726 ,  C11ORF41|25758 ,  TCHH|7062 ,  GJB2|2706 ,  CSRP2|1466 ,  ...

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

    • TEAD3|7005 ,  RGL2|5863 ,  AGPAT5|55326 ,  PDE12|201626 ,  NAT1|9 ,  ...

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

    • NBPF15|284565 ,  OR6W1P|89883 ,  LOC728554|728554 ,  LOC728989|728989 ,  POTEE|445582 ,  ...

  • 37 genes correlated to 'GENDER'.

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

  • 388 genes correlated to 'HISTOLOGICAL.TYPE'.

    • PLAGL2|5326 ,  POFUT1|23509 ,  SLC5A6|8884 ,  SDR16C5|195814 ,  UQCC|55245 ,  ...

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

    • DFNB31|25861 ,  SKP2|6502 ,  CDK19|23097 ,  PLSCR4|57088 ,  LRRFIP2|9209 ,  ...

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

    • AGAP11|119385 ,  LOC728875|728875 ,  LOC150776|150776 ,  RRN3P2|653390 ,  LOC100132287|100132287 ,  ...

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

    • RGL2|5863 ,  NPR3|4883 ,  TEAD3|7005 ,  MINPP1|9562 ,  CASP1|834 ,  ...

  • 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=4 older N=1 younger N=3
NEOPLASM DISEASESTAGE ANOVA test N=25        
PATHOLOGY T STAGE Spearman correlation test N=6 higher stage N=6 lower stage N=0
PATHOLOGY N STAGE Spearman correlation test N=49 higher stage N=26 lower stage N=23
PATHOLOGY M STAGE ANOVA test N=123        
GENDER t test N=37 male N=15 female N=22
HISTOLOGICAL TYPE t test N=388 colon mucinous adenocarcinoma N=197 colon adenocarcinoma N=191
RADIATIONS RADIATION REGIMENINDICATION t test N=77 yes N=36 no N=41
COMPLETENESS OF RESECTION ANOVA test N=238        
NUMBER OF LYMPH NODES Spearman correlation test N=38 higher number.of.lymph.nodes N=16 lower number.of.lymph.nodes N=22
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=13)
  censored N = 268
  death N = 60
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

4 genes related to 'AGE'.

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

AGE Mean (SD) 67.05 (13)
  Significant markers N = 4
  pos. correlated 1
  neg. correlated 3
List of 4 genes significantly correlated to 'AGE' by Spearman correlation test

Table S3.  Get Full Table List of 4 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
MTERF|7978 -0.2721 2.069e-08 0.000372
AMH|268 0.2625 9.998e-08 0.0018
MGA|23269 -0.2499 2.582e-07 0.00465
ZNF75A|7627 -0.2379 1.034e-06 0.0186

Figure S1.  Get High-res Image As an example, this figure shows the association of MTERF|7978 to 'AGE'. P value = 2.07e-08 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

25 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 66
  STAGE IA 1
  STAGE II 31
  STAGE IIA 120
  STAGE IIB 9
  STAGE IIC 1
  STAGE III 22
  STAGE IIIA 13
  STAGE IIIB 50
  STAGE IIIC 35
  STAGE IV 42
  STAGE IVA 15
  STAGE IVB 1
     
  Significant markers N = 25
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 1.931e-09 3.48e-05
RGL2|5863 1.824e-08 0.000328
TEAD3|7005 2.673e-08 0.000481
SCN5A|6331 2.699e-08 0.000486
PRSS8|5652 4.336e-08 0.00078
PRH1|5554 9.606e-08 0.00173
C13ORF15|28984 1.094e-07 0.00197
CTNNA1|1495 1.863e-07 0.00335
NOS2|4843 1.946e-07 0.0035
PALM2|114299 3.208e-07 0.00577

Figure S2.  Get High-res Image As an example, this figure shows the association of ZNF845|91664 to 'NEOPLASM.DISEASESTAGE'. P value = 1.93e-09 with ANOVA analysis.

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

6 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 70
  3 284
  4 49
     
  Significant markers N = 6
  pos. correlated 6
  neg. correlated 0
List of 6 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

Table S7.  Get Full Table List of 6 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
C10ORF114|399726 0.2476 4.495e-07 0.00809
C11ORF41|25758 0.2403 8.561e-07 0.0154
TCHH|7062 0.2436 1.201e-06 0.0216
GJB2|2706 0.2358 1.226e-06 0.0221
CSRP2|1466 0.2352 1.299e-06 0.0234
RIMKLB|57494 0.2297 2.328e-06 0.0419

Figure S3.  Get High-res Image As an example, this figure shows the association of C10ORF114|399726 to 'PATHOLOGY.T.STAGE'. P value = 4.49e-07 with Spearman correlation analysis.

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

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

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

PATHOLOGY.N.STAGE Mean (SD) 0.59 (0.77)
  N
  0 242
  1 99
  2 73
     
  Significant markers N = 49
  pos. correlated 26
  neg. correlated 23
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 0.2973 6.749e-10 1.21e-05
RGL2|5863 0.2963 7.762e-10 1.4e-05
AGPAT5|55326 -0.2859 3.13e-09 5.63e-05
PDE12|201626 -0.2849 3.594e-09 6.47e-05
NAT1|9 -0.2819 5.307e-09 9.55e-05
NPR3|4883 0.2965 1.358e-08 0.000244
MINPP1|9562 -0.2695 2.547e-08 0.000458
GSR|2936 -0.2694 2.583e-08 0.000465
C13ORF15|28984 0.2664 3.696e-08 0.000665
PBK|55872 -0.2647 4.744e-08 0.000853

Figure S4.  Get High-res Image As an example, this figure shows the association of TEAD3|7005 to 'PATHOLOGY.N.STAGE'. P value = 6.75e-10 with Spearman correlation analysis.

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

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

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

PATHOLOGY.M.STAGE Labels N
  M0 310
  M1 49
  M1A 7
  M1B 1
  MX 41
     
  Significant markers N = 123
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 1.96e-10 3.53e-06
OR6W1P|89883 2.423e-09 4.36e-05
LOC728554|728554 4.733e-09 8.52e-05
LOC728989|728989 1.145e-08 0.000206
POTEE|445582 1.158e-08 0.000208
FUNDC2P2|388965 1.219e-08 0.000219
TUBA4B|80086 1.566e-08 0.000282
LOC90586|90586 2.156e-08 0.000388
C2ORF27B|408029 2.221e-08 4e-04
PPIAL4D|645142 2.571e-08 0.000463

Figure S5.  Get High-res Image As an example, this figure shows the association of NBPF15|284565 to 'PATHOLOGY.M.STAGE'. P value = 1.96e-10 with ANOVA analysis.

Clinical variable #7: 'GENDER'

37 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 198
  MALE 217
     
  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 -42.88 4.838e-136 8.71e-132 0.9964
ZFY|7544 45.59 4.047e-116 7.28e-112 0.9963
RPS4Y1|6192 37.8 8.364e-112 1.51e-107 0.9968
DDX3Y|8653 42.93 2.794e-84 5.03e-80 0.9981
KDM5D|8284 40.92 5.668e-76 1.02e-71 0.9981
TSIX|9383 -21.1 1.99e-61 3.58e-57 0.959
PRKY|5616 21.36 3.315e-61 5.97e-57 0.944
NLGN4Y|22829 24.85 5.03e-55 9.05e-51 0.9825
CYORF15A|246126 29.72 7.927e-52 1.43e-47 0.9922
EIF1AY|9086 29.27 1.569e-44 2.82e-40 0.9942

Figure S6.  Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 4.84e-136 with T-test analysis.

Clinical variable #8: 'HISTOLOGICAL.TYPE'

388 genes related to 'HISTOLOGICAL.TYPE'.

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

HISTOLOGICAL.TYPE Labels N
  COLON ADENOCARCINOMA 359
  COLON MUCINOUS ADENOCARCINOMA 54
     
  Significant markers N = 388
  Higher in COLON MUCINOUS ADENOCARCINOMA 197
  Higher in COLON ADENOCARCINOMA 191
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 -9.17 4.654e-14 8.38e-10 0.8104
POFUT1|23509 -8.77 1.6e-13 2.88e-09 0.7833
SLC5A6|8884 -8.65 3.826e-13 6.89e-09 0.7898
SDR16C5|195814 8.27 7.896e-13 1.42e-08 0.7666
UQCC|55245 -8.46 1.196e-12 2.15e-08 0.8009
MUC2|4583 8.17 2.727e-12 4.91e-08 0.8065
CREB3L1|90993 8.28 2.752e-12 4.95e-08 0.7911
TAF4|6874 -8.01 9.54e-12 1.72e-07 0.7825
TRPC4AP|26133 -7.85 9.795e-12 1.76e-07 0.7581
AGR3|155465 7.66 1.279e-11 2.3e-07 0.7428

Figure S7.  Get High-res Image As an example, this figure shows the association of PLAGL2|5326 to 'HISTOLOGICAL.TYPE'. P value = 4.65e-14 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 412
     
  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 -16.48 2.828e-47 4.62e-43 0.7888
SKP2|6502 18 3.872e-39 6.32e-35 0.8503
CDK19|23097 -17.6 2.009e-28 3.28e-24 0.8511
PLSCR4|57088 -11.84 2.899e-27 4.73e-23 0.7065
LRRFIP2|9209 -15.53 8.772e-25 1.43e-20 0.8422
AMPH|273 -11.43 1.988e-24 3.24e-20 0.7374
COMMD4|54939 16.28 3.03e-24 4.95e-20 0.8325
DNASE2|1777 -11.31 6.566e-24 1.07e-19 0.7314
FAM24B|196792 -11.86 5.631e-23 9.19e-19 0.7506
PIGF|5281 10.7 1.011e-22 1.65e-18 0.7427

Figure S8.  Get High-res Image As an example, this figure shows the association of DFNB31|25861 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 2.83e-47 with T-test analysis.

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

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

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

COMPLETENESS.OF.RESECTION Labels N
  R0 293
  R1 3
  R2 23
  RX 24
     
  Significant markers N = 238
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
AGAP11|119385 1.319e-10 2.37e-06
LOC728875|728875 1.355e-10 2.44e-06
LOC150776|150776 1.37e-10 2.46e-06
RRN3P2|653390 1.611e-10 2.9e-06
LOC100132287|100132287 1.75e-10 3.15e-06
NSUN5P1|155400 2.173e-10 3.91e-06
LOC100133331|100133331 2.411e-10 4.34e-06
PMS2L2|5380 4.762e-10 8.57e-06
PMS2CL|441194 5.388e-10 9.69e-06
LOC100190939|100190939 1.627e-09 2.93e-05

Figure S9.  Get High-res Image As an example, this figure shows the association of AGAP11|119385 to 'COMPLETENESS.OF.RESECTION'. P value = 1.32e-10 with ANOVA analysis.

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

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

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

NUMBER.OF.LYMPH.NODES Mean (SD) 2.07 (4.5)
  Significant markers N = 38
  pos. correlated 16
  neg. correlated 22
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
RGL2|5863 0.2987 1.686e-09 3.03e-05
NPR3|4883 0.3129 5.975e-09 0.000108
TEAD3|7005 0.2877 6.913e-09 0.000124
MINPP1|9562 -0.2841 1.076e-08 0.000194
CASP1|834 -0.2785 2.133e-08 0.000384
C5ORF23|79614 0.2785 4.143e-08 0.000745
PALM2|114299 0.2709 7.198e-08 0.0013
AGPAT5|55326 -0.2676 7.719e-08 0.00139
CXCL11|6373 -0.2639 1.23e-07 0.00221
SHC1|6464 0.2603 1.785e-07 0.00321

Figure S10.  Get High-res Image As an example, this figure shows the association of RGL2|5863 to 'NUMBER.OF.LYMPH.NODES'. P value = 1.69e-09 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 = 415

  • Number of genes = 17999

  • 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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