Correlation between mRNAseq expression and clinical features
Colon Adenocarcinoma (Primary solid tumor)
23 September 2013  |  analyses__2013_09_23
Maintainer Information
Citation Information
doi:10.7908/C1H993GR
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1H993GR
Overview
Introduction

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

Summary

Testing the association between 18042 genes and 11 clinical features across 226 samples, statistically thresholded by Q value < 0.05, 8 clinical features related to at least one genes.

  • 10 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • PRH1|5554 ,  ZNF845|91664 ,  RB1|5925 ,  TDRD12|91646 ,  PRH2|5555 ,  ...

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

    • TEAD3|7005 ,  ZBTB20|26137 ,  UNG|7374 ,  PDE12|201626 ,  MAPKAPK3|7867 ,  ...

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

    • RB1|5925 ,  ZNF845|91664 ,  FAM171A1|221061 ,  TDRD12|91646 ,  CCDC122|160857 ,  ...

  • 31 genes correlated to 'GENDER'.

    • XIST|7503 ,  ZFY|7544 ,  KDM5D|8284 ,  RPS4Y1|6192 ,  PRKY|5616 ,  ...

  • 44 genes correlated to 'HISTOLOGICAL.TYPE'.

    • MAP3K6|9064 ,  MEIS2|4212 ,  KCTD15|79047 ,  CAMTA2|23125 ,  ZNF280C|55609 ,  ...

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

    • SKP2|6502 ,  DFNB31|25861 ,  COMMD4|54939 ,  TRIM16|10626 ,  CDK19|23097 ,  ...

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

    • ZNHIT2|741 ,  PAIP2B|400961 ,  DOPEY2|9980

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

    • TEAD3|7005 ,  ZBTB20|26137 ,  RGL2|5863 ,  NIPAL4|348938 ,  TGFBR2|7048 ,  ...

  • No genes correlated to 'Time to Death', 'AGE', and 'PATHOLOGY.T.STAGE'.

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=0        
NEOPLASM DISEASESTAGE ANOVA test N=10        
PATHOLOGY T STAGE Spearman correlation test   N=0        
PATHOLOGY N STAGE Spearman correlation test N=15 higher stage N=9 lower stage N=6
PATHOLOGY M STAGE ANOVA test N=12        
GENDER t test N=31 male N=13 female N=18
HISTOLOGICAL TYPE t test N=44 colon mucinous adenocarcinoma N=26 colon adenocarcinoma N=18
RADIATIONS RADIATION REGIMENINDICATION t test N=76 yes N=30 no N=46
COMPLETENESS OF RESECTION ANOVA test N=3        
NUMBER OF LYMPH NODES Spearman correlation test N=8 higher number.of.lymph.nodes N=7 lower number.of.lymph.nodes N=1
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=13.3)
  censored N = 174
  death N = 44
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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

AGE Mean (SD) 65.09 (13)
  Significant markers N = 0
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

10 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S3.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 33
  STAGE IA 1
  STAGE II 18
  STAGE IIA 67
  STAGE IIB 3
  STAGE IIC 1
  STAGE III 9
  STAGE IIIA 5
  STAGE IIIB 34
  STAGE IIIC 16
  STAGE IV 17
  STAGE IVA 14
  STAGE IVB 1
     
  Significant markers N = 10
List of 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S4.  Get Full Table List of 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
PRH1|5554 2.121e-09 3.83e-05
ZNF845|91664 4.877e-09 8.8e-05
RB1|5925 5.763e-09 0.000104
TDRD12|91646 1.298e-08 0.000234
PRH2|5555 6.244e-08 0.00113
USP26|83844 9.582e-07 0.0173
STK19|8859 9.699e-07 0.0175
PDE12|201626 1.989e-06 0.0359
FAM171A1|221061 2.407e-06 0.0434
ALDH2|217 2.61e-06 0.0471

Figure S1.  Get High-res Image As an example, this figure shows the association of PRH1|5554 to 'NEOPLASM.DISEASESTAGE'. P value = 2.12e-09 with ANOVA analysis.

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

No gene related to 'PATHOLOGY.T.STAGE'.

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.92 (0.64)
  N
  0 1
  1 5
  2 34
  3 156
  4 29
     
  Significant markers N = 0
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.56 (0.74)
  N
  0 132
  1 59
  2 34
     
  Significant markers N = 15
  pos. correlated 9
  neg. correlated 6
List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

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

SpearmanCorr corrP Q
TEAD3|7005 0.3579 3.349e-08 0.000604
ZBTB20|26137 0.3553 4.27e-08 0.00077
UNG|7374 -0.3497 7.171e-08 0.00129
PDE12|201626 -0.3421 1.421e-07 0.00256
MAPKAPK3|7867 -0.3415 1.505e-07 0.00271
ZFAND3|60685 0.3394 1.81e-07 0.00327
RGL2|5863 0.3297 4.177e-07 0.00753
TCHH|7062 0.3262 7.142e-07 0.0129
COL11A2|1302 0.3195 1.101e-06 0.0199
DPYSL4|10570 0.3171 1.413e-06 0.0255

Figure S2.  Get High-res Image As an example, this figure shows the association of TEAD3|7005 to 'PATHOLOGY.N.STAGE'. P value = 3.35e-08 with Spearman correlation analysis.

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

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

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

PATHOLOGY.M.STAGE Labels N
  M0 153
  M1 24
  M1A 6
  M1B 1
  MX 38
     
  Significant markers N = 12
List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S9.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
RB1|5925 1.482e-12 2.67e-08
ZNF845|91664 4.2e-09 7.58e-05
FAM171A1|221061 4.931e-09 8.89e-05
TDRD12|91646 5.486e-09 9.9e-05
CCDC122|160857 3.346e-08 0.000604
ZNF558|148156 5.04e-08 0.000909
TMEM185A|84548 6.46e-08 0.00117
ZNF675|171392 9.646e-08 0.00174
C13ORF31|144811 1.838e-07 0.00331
MRPS31|10240 1.008e-06 0.0182

Figure S3.  Get High-res Image As an example, this figure shows the association of RB1|5925 to 'PATHOLOGY.M.STAGE'. P value = 1.48e-12 with ANOVA analysis.

Clinical variable #7: 'GENDER'

31 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 100
  MALE 126
     
  Significant markers N = 31
  Higher in MALE 13
  Higher in FEMALE 18
List of top 10 genes differentially expressed by 'GENDER'

Table S11.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
XIST|7503 -43.44 1.167e-100 2.1e-96 1
ZFY|7544 47.21 7.489e-100 1.35e-95 0.9994
KDM5D|8284 58.9 7.489e-91 1.35e-86 1
RPS4Y1|6192 40.59 1.416e-87 2.55e-83 1
PRKY|5616 29.9 6.224e-75 1.12e-70 0.9959
TMSB4Y|9087 29.93 1.186e-60 2.14e-56 0.992
CYORF15A|246126 37.73 4.685e-60 8.45e-56 1
DDX3Y|8653 48.11 1.662e-58 3e-54 1
TSIX|9383 -21.65 2.501e-49 4.51e-45 0.9984
NLGN4Y|22829 31.58 1.028e-48 1.85e-44 0.9989

Figure S4.  Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 1.17e-100 with T-test analysis.

Clinical variable #8: 'HISTOLOGICAL.TYPE'

44 genes related to 'HISTOLOGICAL.TYPE'.

Table S12.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  COLON ADENOCARCINOMA 196
  COLON MUCINOUS ADENOCARCINOMA 30
     
  Significant markers N = 44
  Higher in COLON MUCINOUS ADENOCARCINOMA 26
  Higher in COLON ADENOCARCINOMA 18
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

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

T(pos if higher in 'COLON MUCINOUS ADENOCARCINOMA') ttestP Q AUC
MAP3K6|9064 6.4 3.975e-08 0.000717 0.7728
MEIS2|4212 6.33 4.026e-08 0.000726 0.7599
KCTD15|79047 6.17 5.999e-08 0.00108 0.7384
CAMTA2|23125 6.16 6.592e-08 0.00119 0.7469
ZNF280C|55609 -6.2 1.01e-07 0.00182 0.777
RNF125|54941 6.11 1.256e-07 0.00226 0.749
ERN2|10595 5.79 1.318e-07 0.00238 0.7139
NUCB2|4925 6.19 1.414e-07 0.00255 0.7971
CAPZB|832 5.98 1.782e-07 0.00321 0.7461
RAB13|5872 6.21 1.868e-07 0.00337 0.7927

Figure S5.  Get High-res Image As an example, this figure shows the association of MAP3K6|9064 to 'HISTOLOGICAL.TYPE'. P value = 3.97e-08 with T-test analysis.

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

76 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S14.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 3
  YES 223
     
  Significant markers N = 76
  Higher in YES 30
  Higher in NO 46
List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S15.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
SKP2|6502 13.1 6.315e-27 1.03e-22 0.8356
DFNB31|25861 -12.23 1.169e-26 1.91e-22 0.8027
COMMD4|54939 12.82 7.11e-23 1.16e-18 0.8281
TRIM16|10626 12.56 5.195e-22 8.48e-18 0.7892
CDK19|23097 -12.03 3.3e-21 5.39e-17 0.8401
HEXB|3074 17.66 2.673e-20 4.36e-16 0.9073
FAM24B|196792 -10.11 5.235e-19 8.55e-15 0.8024
LY6G6D|58530 -10.92 2.639e-17 4.31e-13 0.7897
IGF2BP3|10643 13.23 2.986e-16 4.87e-12 0.7922
AMPH|273 -8.79 5.154e-16 8.41e-12 0.7511

Figure S6.  Get High-res Image As an example, this figure shows the association of SKP2|6502 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 6.32e-27 with T-test analysis.

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

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

Table S16.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 134
  R1 1
  R2 2
  RX 24
     
  Significant markers N = 3
List of 3 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S17.  Get Full Table List of 3 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
ZNHIT2|741 5.02e-13 9.06e-09
PAIP2B|400961 3.518e-08 0.000635
DOPEY2|9980 1.915e-06 0.0345

Figure S7.  Get High-res Image As an example, this figure shows the association of ZNHIT2|741 to 'COMPLETENESS.OF.RESECTION'. P value = 5.02e-13 with ANOVA analysis.

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

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

Table S18.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2 (4.7)
  Significant markers N = 8
  pos. correlated 7
  neg. correlated 1
List of 8 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

Table S19.  Get Full Table List of 8 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
TEAD3|7005 0.3625 9.911e-08 0.00179
ZBTB20|26137 0.3525 2.331e-07 0.0042
RGL2|5863 0.3525 2.336e-07 0.00421
NIPAL4|348938 0.353 2.398e-07 0.00432
TGFBR2|7048 0.3328 1.15e-06 0.0207
PSME1|5720 -0.3302 1.413e-06 0.0255
TACSTD2|4070 0.3239 2.284e-06 0.0412
TMEM105|284186 0.3215 2.754e-06 0.0497

Figure S8.  Get High-res Image As an example, this figure shows the association of TEAD3|7005 to 'NUMBER.OF.LYMPH.NODES'. P value = 9.91e-08 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.clin.merged.picked.txt

  • Number of patients = 226

  • Number of genes = 18042

  • 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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