Correlation between mRNAseq expression and clinical features
Bladder Urothelial Carcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
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/C1765D1M
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 18282 genes and 11 clinical features across 216 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one genes.

  • 1 gene correlated to 'Time to Death'.

    • LOC285359|285359

  • 2 genes correlated to 'AGE'.

    • TRIM38|10475 ,  MTRF1|9617

  • 68 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • SFRP4|6424 ,  SFRP2|6423 ,  GSTM5|2949 ,  SSC5D|284297 ,  KLF9|687 ,  ...

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

    • CRISPLD2|83716 ,  IGF1|3479 ,  TPST1|8460 ,  TIMP2|7077 ,  SSC5D|284297 ,  ...

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

    • GOLGA4|2803 ,  MCEE|84693 ,  CREB3L2|64764 ,  ZNRD1|30834 ,  C6ORF141|135398 ,  ...

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

    • ATP5G2|517 ,  TMEM104|54868 ,  TTC7A|57217 ,  ITGAX|3687 ,  HK3|3101 ,  ...

  • 4 genes correlated to 'GENDER'.

    • CYORF15A|246126 ,  HDHD1A|8226 ,  NRG1|3084 ,  EID2B|126272

  • 4 genes correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

    • LOC283070|283070 ,  CNP|1267 ,  TXNDC9|10190 ,  APBB1IP|54518

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

    • C6ORF141|135398 ,  PRR15L|79170 ,  ANXA9|8416 ,  MYH14|79784 ,  MCEE|84693 ,  ...

  • 619 genes correlated to 'RACE'.

    • GPR176|11245 ,  DEGS1|8560 ,  ELOVL4|6785 ,  LOX|4015 ,  FKBP9L|360132 ,  ...

  • No genes correlated to 'NUMBERPACKYEARSSMOKED'

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=1 shorter survival N=0 longer survival N=1
AGE Spearman correlation test N=2 older N=0 younger N=2
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=68        
PATHOLOGY T STAGE Spearman correlation test N=133 higher stage N=128 lower stage N=5
PATHOLOGY N STAGE Spearman correlation test N=36 higher stage N=18 lower stage N=18
PATHOLOGY M STAGE Kruskal-Wallis test N=23        
GENDER Wilcoxon test N=4 male N=4 female N=0
KARNOFSKY PERFORMANCE SCORE Spearman correlation test N=4 higher score N=3 lower score N=1
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
NUMBER OF LYMPH NODES Spearman correlation test N=39 higher number.of.lymph.nodes N=33 lower number.of.lymph.nodes N=6
RACE Kruskal-Wallis test N=619        
Clinical variable #1: 'Time to Death'

One gene related to 'Time to Death'.

Table S1.  Basic characteristics of clinical feature: 'Time to Death'

Time to Death Duration (Months) 0.1-140.8 (median=8.3)
  censored N = 151
  death N = 59
     
  Significant markers N = 1
  associated with shorter survival 0
  associated with longer survival 1
List of one gene differentially expressed by 'Time to Death'

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

HazardRatio Wald_P Q C_index
LOC285359|285359 0.43 9.12e-06 0.17 0.378
Clinical variable #2: 'AGE'

2 genes related to 'AGE'.

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

AGE Mean (SD) 67.67 (11)
  Significant markers N = 2
  pos. correlated 0
  neg. correlated 2
List of 2 genes differentially expressed by 'AGE'

Table S4.  Get Full Table List of 2 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
TRIM38|10475 -0.2999 7.636e-06 0.14
MTRF1|9617 -0.2902 1.531e-05 0.28
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

68 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE 0A 1
  STAGE I 2
  STAGE II 69
  STAGE III 73
  STAGE IV 67
     
  Significant markers N = 68
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
SFRP4|6424 2.615e-08 0.000478
SFRP2|6423 4.957e-08 0.000906
GSTM5|2949 1.153e-07 0.00211
SSC5D|284297 2.286e-07 0.00418
KLF9|687 2.756e-07 0.00504
COL6A3|1293 4.293e-07 0.00785
ISLR2|57611 4.409e-07 0.00806
POSTN|10631 4.625e-07 0.00845
ITGBL1|9358 5.314e-07 0.00971
CCDC80|151887 5.333e-07 0.00975
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

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

PATHOLOGY.T.STAGE Mean (SD) 2.84 (0.72)
  N
  0 1
  1 1
  2 60
  3 101
  4 33
     
  Significant markers N = 133
  pos. correlated 128
  neg. correlated 5
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
CRISPLD2|83716 0.3753 5.964e-08 0.00109
IGF1|3479 0.3743 6.503e-08 0.00119
TPST1|8460 0.3742 6.534e-08 0.00119
TIMP2|7077 0.3678 1.133e-07 0.00207
SSC5D|284297 0.3674 1.175e-07 0.00215
KLF9|687 0.3664 1.282e-07 0.00234
EFEMP1|2202 0.3659 1.34e-07 0.00245
SGIP1|84251 0.3641 1.556e-07 0.00284
CTHRC1|115908 0.3612 1.988e-07 0.00363
LUM|4060 0.3595 2.274e-07 0.00416
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

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

PATHOLOGY.N.STAGE Mean (SD) 0.6 (0.92)
  N
  0 132
  1 21
  2 39
  3 7
     
  Significant markers N = 36
  pos. correlated 18
  neg. correlated 18
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
GOLGA4|2803 0.3584 2.022e-07 0.0037
MCEE|84693 0.3559 2.491e-07 0.00455
CREB3L2|64764 0.3452 5.93e-07 0.0108
ZNRD1|30834 -0.339 9.66e-07 0.0177
C6ORF141|135398 -0.348 1.06e-06 0.0194
GFPT1|2673 0.3378 1.065e-06 0.0195
IL1R1|3554 0.3321 1.649e-06 0.0301
ASPHD2|57168 -0.3293 2.049e-06 0.0375
RPF2|84154 -0.3278 2.286e-06 0.0418
HOXD9|3235 -0.3249 2.846e-06 0.052
Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

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

PATHOLOGY.M.STAGE Labels N
  M0 109
  M1 5
  MX 101
     
  Significant markers N = 23
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
ATP5G2|517 3.823e-07 0.00699
TMEM104|54868 6.369e-07 0.0116
TTC7A|57217 1.416e-06 0.0259
ITGAX|3687 1.551e-06 0.0283
HK3|3101 1.962e-06 0.0359
SUSD3|203328 2.715e-06 0.0496
STAB1|23166 2.88e-06 0.0526
HNRNPA1|3178 4.849e-06 0.0886
SIGLEC1|6614 5.081e-06 0.0929
CHI3L1|1116 5.557e-06 0.102
Clinical variable #7: 'GENDER'

4 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 51
  MALE 165
     
  Significant markers N = 4
  Higher in MALE 4
  Higher in FEMALE 0
List of 4 genes differentially expressed by 'GENDER'

Table S14.  Get Full Table List of 4 genes differentially expressed by 'GENDER'. 15 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
CYORF15A|246126 1485 4.604e-07 0.00841 1
HDHD1A|8226 2234 5.189e-07 0.00947 0.7329
NRG1|3084 2313 8.409e-06 0.154 0.7091
EID2B|126272 2500 1.209e-05 0.221 0.7029
Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

4 genes related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S15.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 79.84 (15)
  Significant markers N = 4
  pos. correlated 3
  neg. correlated 1
List of 4 genes differentially expressed by 'KARNOFSKY.PERFORMANCE.SCORE'

Table S16.  Get Full Table List of 4 genes significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

SpearmanCorr corrP Q
LOC283070|283070 -0.6391 2.981e-08 0.000545
CNP|1267 0.5577 3.031e-06 0.0554
TXNDC9|10190 0.5269 1.289e-05 0.236
APBB1IP|54518 0.5251 1.393e-05 0.255
Clinical variable #9: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

Table S17.  Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED Mean (SD) 38.27 (28)
  Significant markers N = 0
Clinical variable #10: 'NUMBER.OF.LYMPH.NODES'

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

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

NUMBER.OF.LYMPH.NODES Mean (SD) 1.54 (3.2)
  Significant markers N = 39
  pos. correlated 33
  neg. correlated 6
List of top 10 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S19.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
C6ORF141|135398 -0.429 3.872e-08 0.000708
PRR15L|79170 0.3944 2.065e-07 0.00378
ANXA9|8416 0.3917 2.538e-07 0.00464
MYH14|79784 0.3904 2.805e-07 0.00513
MCEE|84693 0.3869 3.651e-07 0.00667
GDPD3|79153 0.3841 4.5e-07 0.00823
CREB3L2|64764 0.3819 5.332e-07 0.00974
IL1R1|3554 0.3799 6.172e-07 0.0113
TTYH1|57348 0.3755 9.178e-07 0.0168
SLC44A2|57153 0.3739 9.506e-07 0.0174
Clinical variable #11: 'RACE'

619 genes related to 'RACE'.

Table S20.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  ASIAN 22
  BLACK OR AFRICAN AMERICAN 12
  WHITE 169
     
  Significant markers N = 619
List of top 10 genes differentially expressed by 'RACE'

Table S21.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

ANOVA_P Q
GPR176|11245 1.259e-09 2.3e-05
DEGS1|8560 2.751e-09 5.03e-05
ELOVL4|6785 5.378e-09 9.83e-05
LOX|4015 8.8e-09 0.000161
FKBP9L|360132 1.174e-08 0.000215
GNB4|59345 1.186e-08 0.000217
BVES|11149 1.72e-08 0.000314
DENND2D|79961 1.795e-08 0.000328
OSMR|9180 1.988e-08 0.000363
GAS1|2619 2.383e-08 0.000435
Methods & Data
Input
  • Expresson data file = BLCA-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt

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

  • Number of patients = 216

  • Number of genes = 18282

  • 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)