Correlation between mRNAseq expression and clinical features
Colorectal Adenocarcinoma (Primary solid tumor)
16 April 2014  |  analyses__2014_04_16
Maintainer Information
Citation Information
doi:10.7908/C13T9FTT
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/C13T9FTT
Overview
Introduction

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

Summary

Testing the association between 18030 genes and 12 clinical features across 593 samples, statistically thresholded by Q value < 0.05, 11 clinical features related to at least one genes.

  • 9 genes correlated to 'AGE'.

    • MTERF|7978 ,  AMH|268 ,  MGA|23269 ,  CNTD2|79935 ,  ZNF75A|7627 ,  ...

  • 136 genes correlated to 'PRIMARY.SITE.OF.DISEASE'.

    • DRD5|1816 ,  ZNF141|7700 ,  ZNF530|348327 ,  ELAVL2|1993 ,  MAP7D2|256714 ,  ...

  • 72 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • C5ORF23|79614 ,  C13ORF15|28984 ,  C2CD4A|145741 ,  TYMS|7298 ,  ZNF845|91664 ,  ...

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

    • SCG2|7857 ,  CSRP2|1466 ,  C5ORF23|79614 ,  LOC100126784|100126784 ,  SOX11|6664 ,  ...

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

    • TEAD3|7005 ,  GSR|2936 ,  C5ORF23|79614 ,  CASP1|834 ,  RGL2|5863 ,  ...

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

    • OR6W1P|89883 ,  NBPF15|284565 ,  FUNDC2P2|388965 ,  POTEE|445582 ,  SPIN2A|54466 ,  ...

  • 43 genes correlated to 'GENDER'.

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

  • 1007 genes correlated to 'HISTOLOGICAL.TYPE'.

    • AQP3|360 ,  SLC19A3|80704 ,  PLAGL2|5326 ,  POFUT1|23509 ,  ASCL2|430 ,  ...

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

    • DCDC2B|149069 ,  HIST1H2AE|3012 ,  ZNF813|126017 ,  MSLNL|401827 ,  BEST3|144453 ,  ...

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

    • LOC150776|150776 ,  RRN3P2|653390 ,  AGAP11|119385 ,  PMS2L2|5380 ,  POLR2J4|84820 ,  ...

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

    • GSR|2936 ,  C5ORF23|79614 ,  CASP1|834 ,  TEAD3|7005 ,  CXCL2|2920 ,  ...

  • 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=9 older N=3 younger N=6
PRIMARY SITE OF DISEASE t test N=136 rectum N=99 colon N=37
NEOPLASM DISEASESTAGE ANOVA test N=72        
PATHOLOGY T STAGE Spearman correlation test N=106 higher stage N=100 lower stage N=6
PATHOLOGY N STAGE Spearman correlation test N=176 higher stage N=121 lower stage N=55
PATHOLOGY M STAGE ANOVA test N=301        
GENDER t test N=43 male N=16 female N=27
HISTOLOGICAL TYPE ANOVA test N=1007        
RADIATIONS RADIATION REGIMENINDICATION t test N=8 yes N=4 no N=4
COMPLETENESS OF RESECTION ANOVA test N=364        
NUMBER OF LYMPH NODES Spearman correlation test N=106 higher number.of.lymph.nodes N=61 lower number.of.lymph.nodes N=45
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=16)
  censored N = 439
  death N = 103
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

9 genes related to 'AGE'.

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

AGE Mean (SD) 66.55 (13)
  Significant markers N = 9
  pos. correlated 3
  neg. correlated 6
List of 9 genes significantly correlated to 'AGE' by Spearman correlation test

Table S3.  Get Full Table List of 9 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
MTERF|7978 -0.2424 2.525e-09 4.55e-05
AMH|268 0.2371 9.221e-09 0.000166
MGA|23269 -0.2281 1.986e-08 0.000358
CNTD2|79935 0.2088 3.089e-07 0.00557
ZNF75A|7627 -0.1997 1.009e-06 0.0182
MRE11A|4361 -0.1982 1.193e-06 0.0215
ZNF134|7693 -0.1978 1.257e-06 0.0227
LOC154761|154761 0.1939 2.045e-06 0.0369
RPL39L|116832 -0.1933 2.193e-06 0.0395

Figure S1.  Get High-res Image As an example, this figure shows the association of MTERF|7978 to 'AGE'. P value = 2.53e-09 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'PRIMARY.SITE.OF.DISEASE'

136 genes related to 'PRIMARY.SITE.OF.DISEASE'.

Table S4.  Basic characteristics of clinical feature: 'PRIMARY.SITE.OF.DISEASE'

PRIMARY.SITE.OF.DISEASE Labels N
  COLON 429
  RECTUM 160
     
  Significant markers N = 136
  Higher in RECTUM 99
  Higher in COLON 37
List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

Table S5.  Get Full Table List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

T(pos if higher in 'RECTUM') ttestP Q AUC
DRD5|1816 -8.7 1.336e-15 2.41e-11 0.7302
ZNF141|7700 7.71 6.543e-14 1.18e-09 0.6642
ZNF530|348327 7.54 3.327e-13 6e-09 0.6655
ELAVL2|1993 7.17 4.122e-12 7.43e-08 0.6698
MAP7D2|256714 7.12 5.111e-12 9.21e-08 0.6488
C19ORF46|163183 6.96 1.062e-11 1.91e-07 0.6216
SHROOM4|57477 6.71 6.015e-11 1.08e-06 0.6335
ZNF662|389114 6.72 7.304e-11 1.32e-06 0.6625
ZNF528|84436 6.6 1.81e-10 3.26e-06 0.6638
HOXC6|3223 -6.58 2.996e-10 5.4e-06 0.678

Figure S2.  Get High-res Image As an example, this figure shows the association of DRD5|1816 to 'PRIMARY.SITE.OF.DISEASE'. P value = 1.34e-15 with T-test analysis.

Clinical variable #4: 'NEOPLASM.DISEASESTAGE'

72 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S6.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 101
  STAGE IA 1
  STAGE II 40
  STAGE IIA 163
  STAGE IIB 11
  STAGE IIC 3
  STAGE III 28
  STAGE IIIA 22
  STAGE IIIB 75
  STAGE IIIC 50
  STAGE IV 59
  STAGE IVA 25
  STAGE IVB 1
     
  Significant markers N = 72
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S7.  Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
C5ORF23|79614 6.058e-10 1.09e-05
C13ORF15|28984 1.161e-09 2.09e-05
C2CD4A|145741 4.003e-09 7.22e-05
TYMS|7298 8.854e-09 0.00016
ZNF845|91664 1.011e-08 0.000182
RGL2|5863 1.574e-08 0.000284
TEAD3|7005 1.595e-08 0.000287
CASP1|834 2.175e-08 0.000392
NOS2|4843 2.654e-08 0.000478
TMEM185A|84548 2.913e-08 0.000525

Figure S3.  Get High-res Image As an example, this figure shows the association of C5ORF23|79614 to 'NEOPLASM.DISEASESTAGE'. P value = 6.06e-10 with ANOVA analysis.

Clinical variable #5: 'PATHOLOGY.T.STAGE'

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

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.86 (0.64)
  N
  0 1
  1 19
  2 104
  3 404
  4 63
     
  Significant markers N = 106
  pos. correlated 100
  neg. correlated 6
List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

Table S9.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
SCG2|7857 0.2545 4.071e-10 7.34e-06
CSRP2|1466 0.2439 1.885e-09 3.4e-05
C5ORF23|79614 0.2461 2.944e-09 5.31e-05
LOC100126784|100126784 0.2542 3.725e-09 6.72e-05
SOX11|6664 0.2412 5.152e-09 9.29e-05
SPP1|6696 0.237 5.444e-09 9.81e-05
NALCN|259232 0.25 7.484e-09 0.000135
HTR2B|3357 0.2379 1.163e-08 0.00021
RBP7|116362 0.2326 1.214e-08 0.000219
OLR1|4973 0.2314 1.552e-08 0.00028

Figure S4.  Get High-res Image As an example, this figure shows the association of SCG2|7857 to 'PATHOLOGY.T.STAGE'. P value = 4.07e-10 with Spearman correlation analysis.

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

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

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

PATHOLOGY.N.STAGE Mean (SD) 0.61 (0.77)
  N
  0 337
  1 146
  2 106
     
  Significant markers N = 176
  pos. correlated 121
  neg. correlated 55
List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

Table S11.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
TEAD3|7005 0.2805 4.102e-12 7.4e-08
GSR|2936 -0.2743 1.256e-11 2.26e-07
C5ORF23|79614 0.2688 8.572e-11 1.55e-06
CASP1|834 -0.2542 3.837e-10 6.92e-06
RGL2|5863 0.2533 4.494e-10 8.1e-06
NARS|4677 -0.2433 2.192e-09 3.95e-05
NPR3|4883 0.2618 2.499e-09 4.5e-05
AGPAT5|55326 -0.2418 2.795e-09 5.04e-05
TCHH|7062 0.2481 2.938e-09 5.3e-05
C13ORF15|28984 0.2404 3.433e-09 6.19e-05

Figure S5.  Get High-res Image As an example, this figure shows the association of TEAD3|7005 to 'PATHOLOGY.N.STAGE'. P value = 4.1e-12 with Spearman correlation analysis.

Clinical variable #7: 'PATHOLOGY.M.STAGE'

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

Table S12.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 447
  M1 71
  M1A 9
  M1B 1
  MX 56
     
  Significant markers N = 301
List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S13.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
OR6W1P|89883 8.959e-19 1.62e-14
NBPF15|284565 1.821e-12 3.28e-08
FUNDC2P2|388965 6.856e-12 1.24e-07
POTEE|445582 1.001e-11 1.8e-07
SPIN2A|54466 2.129e-11 3.84e-07
LOC100132832|100132832 3.574e-11 6.44e-07
UBE2NL|389898 4.796e-11 8.64e-07
LOC728554|728554 4.887e-11 8.81e-07
LOC344967|344967 7.757e-11 1.4e-06
C14ORF19|280655 8.183e-11 1.47e-06

Figure S6.  Get High-res Image As an example, this figure shows the association of OR6W1P|89883 to 'PATHOLOGY.M.STAGE'. P value = 8.96e-19 with ANOVA analysis.

Clinical variable #8: 'GENDER'

43 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 275
  MALE 318
     
  Significant markers N = 43
  Higher in MALE 16
  Higher in FEMALE 27
List of top 10 genes differentially expressed by 'GENDER'

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

T(pos if higher in 'MALE') ttestP Q AUC
XIST|7503 -52.46 8.853e-200 1.6e-195 0.9973
ZFY|7544 50.04 1.58e-149 2.85e-145 0.9958
RPS4Y1|6192 43.94 1.166e-146 2.1e-142 0.9967
DDX3Y|8653 47.96 3.244e-108 5.85e-104 0.998
KDM5D|8284 44.02 5.953e-94 1.07e-89 0.9977
TSIX|9383 -26.02 3.343e-92 6.03e-88 0.9641
PRKY|5616 24.07 1.636e-79 2.95e-75 0.9333
NLGN4Y|22829 30.18 3.6e-77 6.49e-73 0.9839
CYORF15A|246126 30.93 1.604e-60 2.89e-56 0.9872
UTY|7404 33.06 9.988e-59 1.8e-54 0.991

Figure S7.  Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 8.85e-200 with T-test analysis.

Clinical variable #9: 'HISTOLOGICAL.TYPE'

1007 genes related to 'HISTOLOGICAL.TYPE'.

Table S16.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  COLON ADENOCARCINOMA 372
  COLON MUCINOUS ADENOCARCINOMA 56
  RECTAL ADENOCARCINOMA 144
  RECTAL MUCINOUS ADENOCARCINOMA 13
     
  Significant markers N = 1007
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S17.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
AQP3|360 3.647e-23 6.58e-19
SLC19A3|80704 5.449e-23 9.82e-19
PLAGL2|5326 2.402e-22 4.33e-18
POFUT1|23509 4.031e-20 7.27e-16
ASCL2|430 6.287e-19 1.13e-14
LY6G6D|58530 8.43e-19 1.52e-14
MAPRE2|10982 2.623e-18 4.73e-14
CKAP4|10970 2.934e-18 5.29e-14
SNHG11|128439 4.099e-18 7.39e-14
SLC5A6|8884 4.275e-18 7.7e-14

Figure S8.  Get High-res Image As an example, this figure shows the association of AQP3|360 to 'HISTOLOGICAL.TYPE'. P value = 3.65e-23 with ANOVA analysis.

Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S18.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 9
  YES 584
     
  Significant markers N = 8
  Higher in YES 4
  Higher in NO 4
List of 8 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S19.  Get Full Table List of 8 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
DCDC2B|149069 11.85 4.657e-11 8.34e-07 0.7503
HIST1H2AE|3012 -13.02 6.947e-11 1.24e-06 0.8187
ZNF813|126017 -9.28 1.087e-07 0.00195 0.7301
MSLNL|401827 8.73 4.907e-07 0.00878 0.7887
BEST3|144453 11.59 1.418e-06 0.0254 0.8881
ZNF701|55762 -8.22 1.557e-06 0.0279 0.7527
CTBP1|1487 8.75 1.724e-06 0.0309 0.847
ZNF586|54807 -7.66 2.744e-06 0.0491 0.746

Figure S9.  Get High-res Image As an example, this figure shows the association of DCDC2B|149069 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 4.66e-11 with T-test analysis.

Clinical variable #11: 'COMPLETENESS.OF.RESECTION'

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

Table S20.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 424
  R1 5
  R2 35
  RX 28
     
  Significant markers N = 364
List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S21.  Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
LOC150776|150776 1.785e-12 3.22e-08
RRN3P2|653390 1.836e-12 3.31e-08
AGAP11|119385 3.5e-12 6.31e-08
PMS2L2|5380 7.435e-12 1.34e-07
POLR2J4|84820 7.694e-12 1.39e-07
PMS2CL|441194 7.981e-12 1.44e-07
GUSBL2|375513 8.149e-12 1.47e-07
GPR89C|728932 1.08e-11 1.95e-07
LOC728875|728875 1.28e-11 2.31e-07
NSUN5P1|155400 1.701e-11 3.07e-07

Figure S10.  Get High-res Image As an example, this figure shows the association of LOC150776|150776 to 'COMPLETENESS.OF.RESECTION'. P value = 1.78e-12 with ANOVA analysis.

Clinical variable #12: 'NUMBER.OF.LYMPH.NODES'

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

Table S22.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.2 (4.7)
  Significant markers N = 106
  pos. correlated 61
  neg. correlated 45
List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

Table S23.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
GSR|2936 -0.2688 1.084e-10 1.95e-06
C5ORF23|79614 0.2728 1.497e-10 2.7e-06
CASP1|834 -0.2651 2.001e-10 3.61e-06
TEAD3|7005 0.2632 2.681e-10 4.83e-06
CXCL2|2920 -0.2587 5.553e-10 1e-05
NPR3|4883 0.2726 1.535e-09 2.77e-05
SHC1|6464 0.2515 1.686e-09 3.04e-05
C2CD4A|145741 -0.2501 2.102e-09 3.79e-05
TCHH|7062 0.2499 6.023e-09 0.000109
RGL2|5863 0.2413 7.816e-09 0.000141

Figure S11.  Get High-res Image As an example, this figure shows the association of GSR|2936 to 'NUMBER.OF.LYMPH.NODES'. P value = 1.08e-10 with Spearman correlation analysis. The straight line presents the best linear regression.

Methods & Data
Input

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

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

  • Number of patients = 593

  • Number of genes = 18030

  • 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

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

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

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] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[4] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[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)
Copyright © 2014 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle