Correlation between mRNAseq expression and clinical features
Colon Adenocarcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1S181CX
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/C1S181CX
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 18015 genes and 12 clinical features across 438 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 11 clinical features related to at least one genes.

  • 3 genes correlated to 'Time to Death'.

    • ANKRD24|170961 ,  GABRD|2563 ,  CCKBR|887

  • 17 genes correlated to 'AGE'.

    • MTERF|7978 ,  AMH|268 ,  MGA|23269 ,  DNM3|26052 ,  FOXD4L1|200350 ,  ...

  • 25 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • RGL2|5863 ,  C5ORF23|79614 ,  GFI1|2672 ,  C2CD4A|145741 ,  TEAD3|7005 ,  ...

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

    • TCHH|7062 ,  C10ORF114|399726 ,  HTR2B|3357 ,  RIMKLB|57494 ,  SOX11|6664 ,  ...

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

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

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

    • NBPF15|284565 ,  FUNDC2P2|388965 ,  POTEE|445582 ,  PPIAL4D|645142 ,  C14ORF19|280655 ,  ...

  • 6 genes correlated to 'GENDER'.

    • CYORF15A|246126 ,  CYORF15B|84663 ,  HDHD1A|8226 ,  NCRNA00183|554203 ,  FRG1B|284802 ,  ...

  • 820 genes correlated to 'HISTOLOGICAL.TYPE'.

    • PLAGL2|5326 ,  SLC19A3|80704 ,  MUC2|4583 ,  UQCC|55245 ,  SLC5A6|8884 ,  ...

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

    • LOC100132287|100132287 ,  LOC150776|150776 ,  NSUN5P1|155400 ,  LOC100133331|100133331 ,  RRN3P2|653390 ,  ...

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

    • RGL2|5863 ,  NPR3|4883 ,  AGPAT5|55326 ,  GSR|2936 ,  TEAD3|7005 ,  ...

  • 16 genes correlated to 'RACE'.

    • LOC441455|441455 ,  ULK4|54986 ,  C14ORF167|55449 ,  CROCCL1|84809 ,  NOTCH2NL|388677 ,  ...

  • No genes correlated to '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=3 shorter survival N=3 longer survival N=0
AGE Spearman correlation test N=17 older N=10 younger N=7
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=25        
PATHOLOGY T STAGE Spearman correlation test N=13 higher stage N=13 lower stage N=0
PATHOLOGY N STAGE Spearman correlation test N=176 higher stage N=89 lower stage N=87
PATHOLOGY M STAGE Kruskal-Wallis test N=202        
GENDER Wilcoxon test N=6 male N=6 female N=0
HISTOLOGICAL TYPE Wilcoxon test N=820 colon mucinous adenocarcinoma N=820 colon adenocarcinoma N=0
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test   N=0        
COMPLETENESS OF RESECTION Kruskal-Wallis test N=359        
NUMBER OF LYMPH NODES Spearman correlation test N=120 higher number.of.lymph.nodes N=55 lower number.of.lymph.nodes N=65
RACE Kruskal-Wallis test N=16        
Clinical variable #1: 'Time to Death'

3 genes 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=20)
  censored N = 333
  death N = 88
     
  Significant markers N = 3
  associated with shorter survival 3
  associated with longer survival 0
List of 3 genes differentially expressed by 'Time to Death'

Table S2.  Get Full Table List of 3 genes significantly associated with 'Time to Death' by Cox regression test

HazardRatio Wald_P Q C_index
ANKRD24|170961 1.42 4.666e-06 0.084 0.646
GABRD|2563 1.53 1.249e-05 0.22 0.664
CCKBR|887 1.41 1.256e-05 0.23 0.665
Clinical variable #2: 'AGE'

17 genes related to 'AGE'.

Table S3.  Basic characteristics of clinical feature: 'AGE'

AGE Mean (SD) 67.08 (13)
  Significant markers N = 17
  pos. correlated 10
  neg. correlated 7
List of top 10 genes differentially expressed by 'AGE'

Table S4.  Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
MTERF|7978 -0.2672 1.572e-08 0.000283
AMH|268 0.2588 7.149e-08 0.00129
MGA|23269 -0.2355 6.39e-07 0.0115
DNM3|26052 -0.2278 1.5e-06 0.027
FOXD4L1|200350 0.2231 3.901e-06 0.0703
ZNF75A|7627 -0.2173 4.791e-06 0.0863
CNTD2|79935 0.2169 4.986e-06 0.0898
LOC154761|154761 0.2165 5.064e-06 0.0912
FGF8|2253 0.2833 5.142e-06 0.0926
AGAP7|653268 0.2152 5.771e-06 0.104
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

25 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S5.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 72
  STAGE IA 1
  STAGE II 27
  STAGE IIA 133
  STAGE IIB 9
  STAGE IIC 1
  STAGE III 21
  STAGE IIIA 12
  STAGE IIIB 55
  STAGE IIIC 38
  STAGE IV 42
  STAGE IVA 17
  STAGE IVB 1
     
  Significant markers N = 25
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S6.  Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
RGL2|5863 7.442e-09 0.000134
C5ORF23|79614 4.379e-07 0.00789
GFI1|2672 8.983e-07 0.0162
C2CD4A|145741 1.1e-06 0.0198
TEAD3|7005 1.183e-06 0.0213
AGPAT5|55326 1.259e-06 0.0227
NPR3|4883 1.715e-06 0.0309
C13ORF15|28984 1.858e-06 0.0335
GSR|2936 2.032e-06 0.0366
NAT1|9 2.085e-06 0.0375
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.89 (0.62)
  N
  1 11
  2 76
  3 299
  4 51
     
  Significant markers N = 13
  pos. correlated 13
  neg. correlated 0
List of top 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S8.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
TCHH|7062 0.2474 3.765e-07 0.00678
C10ORF114|399726 0.242 4.035e-07 0.00727
HTR2B|3357 0.2316 1.858e-06 0.0335
RIMKLB|57494 0.2251 2.007e-06 0.0361
SOX11|6664 0.2276 2.251e-06 0.0405
CSRP2|1466 0.2239 2.268e-06 0.0408
GJB2|2706 0.2233 2.415e-06 0.0435
C5ORF23|79614 0.2229 3.871e-06 0.0697
C11ORF41|25758 0.2171 5.153e-06 0.0928
FSTL3|10272 0.2118 8e-06 0.144
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.59 (0.77)
  N
  0 258
  1 102
  2 77
     
  Significant markers N = 176
  pos. correlated 89
  neg. correlated 87
List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S10.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
AGPAT5|55326 -0.3086 4.25e-11 7.66e-07
NAT1|9 -0.3077 4.889e-11 8.81e-07
GSR|2936 -0.3002 1.502e-10 2.71e-06
TEAD3|7005 0.2981 2.039e-10 3.67e-06
RGL2|5863 0.2913 5.42e-10 9.76e-06
PDE12|201626 -0.2853 1.256e-09 2.26e-05
INTS10|55174 -0.2829 1.749e-09 3.15e-05
PBK|55872 -0.2815 2.186e-09 3.94e-05
NPR3|4883 0.2988 3.589e-09 6.46e-05
CDCA2|157313 -0.2743 5.789e-09 0.000104
Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

Table S11.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 325
  M1 50
  M1A 8
  M1B 1
  MX 47
     
  Significant markers N = 202
List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S12.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
NBPF15|284565 1.978e-09 3.56e-05
FUNDC2P2|388965 2.291e-09 4.13e-05
POTEE|445582 9.262e-09 0.000167
PPIAL4D|645142 1.183e-08 0.000213
C14ORF19|280655 1.904e-08 0.000343
UBE2NL|389898 3.066e-08 0.000552
LAP3|51056 3.197e-08 0.000576
LOC90586|90586 3.619e-08 0.000652
EDARADD|128178 5.289e-08 0.000952
NCRNA00182|100302692 5.665e-08 0.00102
Clinical variable #7: 'GENDER'

6 genes related to 'GENDER'.

Table S13.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 206
  MALE 232
     
  Significant markers N = 6
  Higher in MALE 6
  Higher in FEMALE 0
List of 6 genes differentially expressed by 'GENDER'

Table S14.  Get Full Table List of 6 genes differentially expressed by 'GENDER'. 37 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
CYORF15A|246126 12644 1.064e-29 1.92e-25 0.9909
CYORF15B|84663 9932 4.705e-24 8.47e-20 0.9814
HDHD1A|8226 11077 3.187e-22 5.74e-18 0.7682
NCRNA00183|554203 13242 7.819e-16 1.41e-11 0.7229
FRG1B|284802 30109.5 1.558e-06 0.028 0.6331
C2ORF84|653140 15630 3.77e-06 0.0678 0.6529
Clinical variable #8: 'HISTOLOGICAL.TYPE'

820 genes related to 'HISTOLOGICAL.TYPE'.

Table S15.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  COLON ADENOCARCINOMA 379
  COLON MUCINOUS ADENOCARCINOMA 57
     
  Significant markers N = 820
  Higher in COLON MUCINOUS ADENOCARCINOMA 820
  Higher in COLON ADENOCARCINOMA 0
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S16.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

W(pos if higher in 'COLON MUCINOUS ADENOCARCINOMA') wilcoxontestP Q AUC
PLAGL2|5326 4033 2.338e-14 4.21e-10 0.8133
SLC19A3|80704 4063.5 3.051e-14 5.5e-10 0.8119
MUC2|4583 17504 4.154e-14 7.48e-10 0.8103
UQCC|55245 4311 2.534e-13 4.56e-09 0.8004
SLC5A6|8884 4462 8.88e-13 1.6e-08 0.7935
POFUT1|23509 4538 1.651e-12 2.97e-08 0.7899
CREB3L1|90993 17060 1.72e-12 3.1e-08 0.7897
AQP3|360 16970 3.55e-12 6.39e-08 0.7855
ACSL5|51703 4646 3.938e-12 7.09e-08 0.7849
TOMM34|10953 4723 7.253e-12 1.31e-07 0.7814
Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

No gene related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S17.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 3
  YES 435
     
  Significant markers N = 0
Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

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

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

COMPLETENESS.OF.RESECTION Labels N
  R0 313
  R1 3
  R2 23
  RX 24
     
  Significant markers N = 359
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
LOC100132287|100132287 4.942e-10 8.9e-06
LOC150776|150776 6.606e-10 1.19e-05
NSUN5P1|155400 6.776e-10 1.22e-05
LOC100133331|100133331 7.049e-10 1.27e-05
RRN3P2|653390 7.429e-10 1.34e-05
SPDYE8P|389517 9.012e-10 1.62e-05
LOC339047|339047 1.543e-09 2.78e-05
PMS2L2|5380 1.564e-09 2.82e-05
PMS2CL|441194 2.443e-09 4.4e-05
AGAP11|119385 2.515e-09 4.53e-05
Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

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

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

NUMBER.OF.LYMPH.NODES Mean (SD) 2.02 (4.4)
  Significant markers N = 120
  pos. correlated 55
  neg. correlated 65
List of top 10 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

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 0.2939 1.077e-09 1.94e-05
NPR3|4883 0.3155 1.336e-09 2.41e-05
AGPAT5|55326 -0.2919 1.419e-09 2.56e-05
GSR|2936 -0.2907 1.656e-09 2.98e-05
TEAD3|7005 0.2877 2.468e-09 4.45e-05
NAT1|9 -0.2846 3.717e-09 6.69e-05
MINPP1|9562 -0.2839 4.068e-09 7.33e-05
CASP1|834 -0.2759 1.139e-08 0.000205
INTS10|55174 -0.2687 2.798e-08 0.000504
C5ORF23|79614 0.2717 3.629e-08 0.000653
Clinical variable #12: 'RACE'

16 genes related to 'RACE'.

Table S22.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 11
  BLACK OR AFRICAN AMERICAN 44
  WHITE 213
     
  Significant markers N = 16
List of top 10 genes differentially expressed by 'RACE'

Table S23.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

ANOVA_P Q
LOC441455|441455 9.399e-11 1.69e-06
ULK4|54986 1.303e-09 2.35e-05
C14ORF167|55449 1.348e-09 2.43e-05
CROCCL1|84809 1.1e-08 0.000198
NOTCH2NL|388677 7.653e-08 0.00138
CYP3A5|1577 2.809e-07 0.00506
SPDYE1|285955 4.469e-07 0.00805
PPIL3|53938 5.725e-07 0.0103
SPDYE6|729597 1.106e-06 0.0199
LOC253039|253039 2.948e-06 0.0531
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 = 438

  • Number of genes = 18015

  • 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

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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