Correlation between mRNAseq expression and clinical features
Colorectal Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C13N224X
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/C13N224X
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 18030 genes and 13 clinical features across 593 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 11 clinical features related to at least one genes.

  • 35 genes correlated to 'AGE'.

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

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

    • HOXB13|10481 ,  ZNF530|348327 ,  ZNF141|7700 ,  ZNF528|84436 ,  ELAVL2|1993 ,  ...

  • 102 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • C5ORF23|79614 ,  RGL2|5863 ,  C2CD4A|145741 ,  BEND3|57673 ,  C13ORF15|28984 ,  ...

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

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

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

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

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

    • POTEE|445582 ,  FUNDC2P2|388965 ,  NBPF15|284565 ,  PPIAL4D|645142 ,  SPIN2A|54466 ,  ...

  • 10 genes correlated to 'GENDER'.

    • CYORF15A|246126 ,  CYORF15B|84663 ,  HDHD1A|8226 ,  NCRNA00183|554203 ,  SPESP1|246777 ,  ...

  • 1424 genes correlated to 'HISTOLOGICAL.TYPE'.

    • PLAGL2|5326 ,  POFUT1|23509 ,  SLC19A3|80704 ,  MUC2|4583 ,  SLC5A6|8884 ,  ...

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

    • RRN3P2|653390 ,  PMS2CL|441194 ,  LOC150776|150776 ,  POLR2J4|84820 ,  SCXB|642658 ,  ...

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

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

  • 11 genes correlated to 'RACE'.

    • ULK4|54986 ,  LOC441455|441455 ,  NOTCH2NL|388677 ,  C14ORF167|55449 ,  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=35 older N=8 younger N=27
PRIMARY SITE OF DISEASE Wilcoxon test N=190 rectum N=190 colon N=0
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=102        
PATHOLOGY T STAGE Spearman correlation test N=210 higher stage N=197 lower stage N=13
PATHOLOGY N STAGE Spearman correlation test N=366 higher stage N=267 lower stage N=99
PATHOLOGY M STAGE Kruskal-Wallis test N=470        
GENDER Wilcoxon test N=10 male N=10 female N=0
HISTOLOGICAL TYPE Kruskal-Wallis test N=1424        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test   N=0        
COMPLETENESS OF RESECTION Kruskal-Wallis test N=628        
NUMBER OF LYMPH NODES Spearman correlation test N=240 higher number.of.lymph.nodes N=161 lower number.of.lymph.nodes N=79
RACE Kruskal-Wallis test N=11        
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=18.1)
  censored N = 458
  death N = 106
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

35 genes related to 'AGE'.

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

AGE Mean (SD) 66.55 (13)
  Significant markers N = 35
  pos. correlated 8
  neg. correlated 27
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 -0.2424 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
TGFBR2|7048 -0.1901 3.176e-06 0.0572
Clinical variable #3: 'PRIMARY.SITE.OF.DISEASE'

190 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 = 190
  Higher in RECTUM 190
  Higher in COLON 0
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'

W(pos if higher in 'RECTUM') wilcoxontestP Q AUC
HOXB13|10481 47913 8.811e-14 1.59e-09 0.6997
ZNF530|348327 45572 6.381e-10 1.15e-05 0.6655
ZNF141|7700 45056 9.171e-10 1.65e-05 0.6642
ZNF528|84436 45349.5 9.636e-10 1.74e-05 0.6638
ELAVL2|1993 36930 1.066e-09 1.92e-05 0.6698
ZNF662|389114 45048 1.34e-09 2.42e-05 0.6625
HOXC4|3221 18109.5 1.553e-09 2.8e-05 0.6717
HOXC6|3223 15291 2.482e-09 4.47e-05 0.678
ZNF813|126017 44795 3.149e-09 5.67e-05 0.6587
GPR126|57211 23464 5.047e-09 9.1e-05 0.6566
Clinical variable #4: 'NEOPLASM.DISEASESTAGE'

102 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 35
  STAGE IIA 168
  STAGE IIB 11
  STAGE IIC 3
  STAGE III 27
  STAGE IIIA 22
  STAGE IIIB 76
  STAGE IIIC 50
  STAGE IV 59
  STAGE IVA 25
  STAGE IVB 1
     
  Significant markers N = 102
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 2.825e-09 5.09e-05
RGL2|5863 4.146e-09 7.47e-05
C2CD4A|145741 2.491e-08 0.000449
BEND3|57673 2.798e-08 0.000504
C13ORF15|28984 3.336e-08 0.000601
GSR|2936 1.113e-07 0.00201
LAP3|51056 1.464e-07 0.00264
NPR3|4883 1.505e-07 0.00271
IRF1|3659 1.567e-07 0.00282
CASP1|834 1.978e-07 0.00357
Clinical variable #5: 'PATHOLOGY.T.STAGE'

210 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 = 210
  pos. correlated 197
  neg. correlated 13
List of top 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

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

366 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 = 366
  pos. correlated 267
  neg. correlated 99
List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'

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

470 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 = 470
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
POTEE|445582 3.891e-11 7.01e-07
FUNDC2P2|388965 5.277e-11 9.51e-07
NBPF15|284565 5.798e-11 1.05e-06
PPIAL4D|645142 1.952e-10 3.52e-06
SPIN2A|54466 2.02e-10 3.64e-06
UBE2NL|389898 2.694e-10 4.86e-06
MCART2|147407 5.256e-10 9.47e-06
RPL23AP82|284942 5.744e-10 1.04e-05
LOC344967|344967 6.155e-10 1.11e-05
C14ORF19|280655 8.41e-10 1.52e-05
Clinical variable #8: 'GENDER'

10 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 275
  MALE 318
     
  Significant markers N = 10
  Higher in MALE 10
  Higher in FEMALE 0
List of 10 genes differentially expressed by 'GENDER'

Table S15.  Get Full Table List of 10 genes differentially expressed by 'GENDER'. 42 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
CYORF15A|246126 22917 1.446e-38 2.61e-34 0.9872
CYORF15B|84663 19517 2.096e-33 3.78e-29 0.9804
HDHD1A|8226 20077 6.184e-30 1.11e-25 0.7704
NCRNA00183|554203 23283 8.792e-23 1.58e-18 0.7338
SPESP1|246777 46200 8.184e-08 0.00147 0.6337
FRG1B|284802 54255 2.591e-07 0.00466 0.6227
CD207|50489 29138 4.328e-07 0.00779 0.6239
ZNF578|147660 33742.5 3.932e-06 0.0707 0.6101
C2ORF84|653140 29626.5 5.956e-06 0.107 0.6262
CXORF38|159013 34679 1.376e-05 0.247 0.6034
Clinical variable #9: 'HISTOLOGICAL.TYPE'

1424 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 = 1424
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
PLAGL2|5326 1.53e-19 2.76e-15
POFUT1|23509 1.765e-18 3.18e-14
SLC19A3|80704 1.088e-17 1.96e-13
MUC2|4583 2.586e-17 4.66e-13
SLC5A6|8884 4.648e-17 8.38e-13
GFI1|2672 7.155e-17 1.29e-12
SNHG11|128439 8.494e-17 1.53e-12
ACTR5|79913 1.286e-16 2.32e-12
AQP3|360 1.7e-16 3.06e-12
TAF4|6874 2.413e-16 4.35e-12
Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

No gene 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 = 0
Clinical variable #11: 'COMPLETENESS.OF.RESECTION'

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

Table S19.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 426
  R1 5
  R2 35
  RX 28
     
  Significant markers N = 628
List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S20.  Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
RRN3P2|653390 8.431e-12 1.52e-07
PMS2CL|441194 1.854e-11 3.34e-07
LOC150776|150776 2.039e-11 3.68e-07
POLR2J4|84820 5.027e-11 9.06e-07
SCXB|642658 5.342e-11 9.63e-07
GUSBL2|375513 7.335e-11 1.32e-06
C7ORF28B|221960 7.906e-11 1.42e-06
NSUN5P1|155400 7.971e-11 1.44e-06
CCDC85B|11007 1.017e-10 1.83e-06
AGAP11|119385 1.06e-10 1.91e-06
Clinical variable #12: 'NUMBER.OF.LYMPH.NODES'

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

Table S21.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.2 (4.7)
  Significant markers N = 240
  pos. correlated 161
  neg. correlated 79
List of top 10 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S22.  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
Clinical variable #13: 'RACE'

11 genes related to 'RACE'.

Table S23.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 12
  BLACK OR AFRICAN AMERICAN 39
  WHITE 294
     
  Significant markers N = 11
List of top 10 genes differentially expressed by 'RACE'

Table S24.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

ANOVA_P Q
ULK4|54986 1.939e-10 3.5e-06
LOC441455|441455 2.629e-10 4.74e-06
NOTCH2NL|388677 1.884e-09 3.4e-05
C14ORF167|55449 3.797e-09 6.85e-05
LOC90784|90784 2.14e-07 0.00386
PPIL3|53938 5.524e-07 0.00996
CRYBB2|1415 6.065e-07 0.0109
TMEM232|642987 9.727e-07 0.0175
CYP3A5|1577 1.153e-06 0.0208
ACSM1|116285 3.172e-06 0.0572
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 = 13

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)
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