Correlation between mRNAseq expression and clinical features
Bladder Urothelial Carcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1TM78Z7
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/C1TM78Z7
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 18247 genes and 12 clinical features across 256 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 9 clinical features related to at least one genes.

  • 9 genes correlated to 'AGE'.

    • HAS1|3036 ,  PLN|5350 ,  PLA2G5|5322 ,  MTRF1|9617 ,  CXCL12|6387 ,  ...

  • 126 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • SFRP2|6423 ,  SFRP4|6424 ,  ITGBL1|9358 ,  VCAN|1462 ,  SSC5D|284297 ,  ...

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

    • CCDC80|151887 ,  SSC5D|284297 ,  EFEMP1|2202 ,  CRISPLD2|83716 ,  TIMP2|7077 ,  ...

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

    • COL17A1|1308 ,  CREB3L2|64764 ,  ASPHD2|57168 ,  PEA15|8682 ,  GFPT1|2673 ,  ...

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

    • TSPAN4|7106 ,  SLC25A25|114789 ,  STAB1|23166 ,  ITGAX|3687 ,  TMEM104|54868 ,  ...

  • 3 genes correlated to 'GENDER'.

    • HDHD1A|8226 ,  CYORF15A|246126 ,  CYORF15B|84663

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

    • LOC283070|283070 ,  APBB1IP|54518 ,  PDIA4|9601 ,  TXNDC9|10190 ,  RASGRP1|10125 ,  ...

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

    • GDPD3|79153 ,  C6ORF141|135398 ,  CREB3L2|64764 ,  ANXA9|8416 ,  PRR15L|79170 ,  ...

  • 860 genes correlated to 'RACE'.

    • LOX|4015 ,  DEGS1|8560 ,  GPR176|11245 ,  ALDH1L2|160428 ,  ELOVL4|6785 ,  ...

  • No genes correlated to 'Time to Death', 'NUMBERPACKYEARSSMOKED', and 'ETHNICITY'.

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=9 older N=7 younger N=2
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=126        
PATHOLOGY T STAGE Spearman correlation test N=209 higher stage N=207 lower stage N=2
PATHOLOGY N STAGE Spearman correlation test N=40 higher stage N=19 lower stage N=21
PATHOLOGY M STAGE Kruskal-Wallis test N=51        
GENDER Wilcoxon test N=3 male N=3 female N=0
KARNOFSKY PERFORMANCE SCORE Spearman correlation test N=10 higher score N=8 lower score N=2
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
NUMBER OF LYMPH NODES Spearman correlation test N=31 higher number.of.lymph.nodes N=26 lower number.of.lymph.nodes N=5
RACE Kruskal-Wallis test N=860        
ETHNICITY Wilcoxon test   N=0        
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) 0.1-140.8 (median=8.6)
  censored N = 171
  death N = 77
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

9 genes related to 'AGE'.

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

AGE Mean (SD) 67.59 (11)
  Significant markers N = 9
  pos. correlated 7
  neg. correlated 2
List of 9 genes differentially expressed by 'AGE'

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

SpearmanCorr corrP Q
HAS1|3036 0.3194 7.532e-07 0.0137
PLN|5350 0.2931 2.098e-06 0.0383
PLA2G5|5322 0.2905 3.145e-06 0.0574
MTRF1|9617 -0.2855 3.6e-06 0.0657
CXCL12|6387 0.2805 5.397e-06 0.0985
CRYAB|1410 0.2739 9.102e-06 0.166
FGF7|2252 0.2714 1.105e-05 0.202
TRIM38|10475 -0.2711 1.127e-05 0.206
TAGLN|6876 0.2671 1.543e-05 0.281
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

126 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S4.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE 0A 1
  STAGE I 2
  STAGE II 82
  STAGE III 84
  STAGE IV 83
     
  Significant markers N = 126
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S5.  Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
SFRP2|6423 3.056e-09 5.58e-05
SFRP4|6424 5.682e-09 0.000104
ITGBL1|9358 8.525e-09 0.000156
VCAN|1462 1.647e-08 3e-04
SSC5D|284297 2.106e-08 0.000384
COL10A1|1300 2.915e-08 0.000532
CCDC80|151887 3.68e-08 0.000671
POSTN|10631 4.858e-08 0.000886
COL6A3|1293 5.604e-08 0.00102
CDH11|1009 7.709e-08 0.00141
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.82 (0.71)
  N
  0 1
  1 1
  2 74
  3 121
  4 37
     
  Significant markers N = 209
  pos. correlated 207
  neg. correlated 2
List of top 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S7.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
CCDC80|151887 0.3742 3.447e-09 6.29e-05
SSC5D|284297 0.37 5.262e-09 9.6e-05
EFEMP1|2202 0.3685 6.151e-09 0.000112
CRISPLD2|83716 0.3666 7.452e-09 0.000136
TIMP2|7077 0.3665 7.535e-09 0.000137
IGF1|3479 0.3647 9.041e-09 0.000165
P4HA3|283208 0.361 1.304e-08 0.000238
ITGBL1|9358 0.3606 1.35e-08 0.000246
CTHRC1|115908 0.3604 1.379e-08 0.000252
TPST1|8460 0.3577 1.807e-08 0.00033
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

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

PATHOLOGY.N.STAGE Mean (SD) 0.62 (0.92)
  N
  0 153
  1 25
  2 50
  3 7
     
  Significant markers N = 40
  pos. correlated 19
  neg. correlated 21
List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S9.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
COL17A1|1308 -0.3328 1.757e-07 0.00321
CREB3L2|64764 0.3306 2.129e-07 0.00388
ASPHD2|57168 -0.3242 3.735e-07 0.00681
PEA15|8682 0.3194 5.676e-07 0.0104
GFPT1|2673 0.3168 7.12e-07 0.013
ITGA6|3655 -0.3162 7.456e-07 0.0136
MCEE|84693 0.3136 9.308e-07 0.017
PVRL4|81607 0.3089 1.379e-06 0.0252
GDPD3|79153 0.3087 1.4e-06 0.0255
IL1R1|3554 0.3082 1.458e-06 0.0266
Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

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

PATHOLOGY.M.STAGE Labels N
  M0 127
  M1 7
  MX 121
     
  Significant markers N = 51
List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S11.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
TSPAN4|7106 5.238e-07 0.00956
SLC25A25|114789 6.734e-07 0.0123
STAB1|23166 6.81e-07 0.0124
ITGAX|3687 8.322e-07 0.0152
TMEM104|54868 9.461e-07 0.0173
RENBP|5973 1.118e-06 0.0204
HK3|3101 1.316e-06 0.024
TTC7A|57217 1.862e-06 0.034
FPR1|2357 2.265e-06 0.0413
C5ORF43|643155 2.374e-06 0.0433
Clinical variable #7: 'GENDER'

3 genes related to 'GENDER'.

Table S12.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 64
  MALE 192
     
  Significant markers N = 3
  Higher in MALE 3
  Higher in FEMALE 0
List of 3 genes differentially expressed by 'GENDER'

Table S13.  Get Full Table List of 3 genes differentially expressed by 'GENDER'. 17 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
HDHD1A|8226 3206 1.273e-08 0.000232 0.7377
CYORF15A|246126 2096 2.973e-08 0.000542 0.9976
CYORF15B|84663 1342 7.703e-06 0.14 0.9985
Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

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

Table S14.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 79.36 (16)
  Significant markers N = 10
  pos. correlated 8
  neg. correlated 2
List of 10 genes differentially expressed by 'KARNOFSKY.PERFORMANCE.SCORE'

Table S15.  Get Full Table List of 10 genes significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

SpearmanCorr corrP Q
LOC283070|283070 -0.579 2.804e-08 0.000512
APBB1IP|54518 0.5199 1.071e-06 0.0195
PDIA4|9601 0.5018 2.863e-06 0.0522
TXNDC9|10190 0.5008 3.026e-06 0.0552
RASGRP1|10125 0.4992 3.282e-06 0.0599
DGKA|1606 -0.498 3.501e-06 0.0639
TMED5|50999 0.4865 6.292e-06 0.115
MCOLN2|255231 0.4879 7.804e-06 0.142
PDIA6|10130 0.4718 1.297e-05 0.237
NUCB2|4925 0.4686 1.511e-05 0.276
Clinical variable #9: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

Table S16.  Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED Mean (SD) 38.12 (28)
  Significant markers N = 0
Clinical variable #10: 'NUMBER.OF.LYMPH.NODES'

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

Table S17.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.17 (7.8)
  Significant markers N = 31
  pos. correlated 26
  neg. correlated 5
List of top 10 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S18.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
GDPD3|79153 0.3677 1.234e-07 0.00225
C6ORF141|135398 -0.37 2.737e-07 0.00499
CREB3L2|64764 0.3468 6.792e-07 0.0124
ANXA9|8416 0.3438 8.614e-07 0.0157
PRR15L|79170 0.3437 9.293e-07 0.017
KCNG1|3755 0.3406 1.103e-06 0.0201
MCEE|84693 0.3396 1.194e-06 0.0218
CLDN4|1364 0.3391 1.242e-06 0.0227
SLC44A2|57153 0.3387 1.282e-06 0.0234
ITGA6|3655 -0.3381 1.336e-06 0.0244
Clinical variable #11: 'RACE'

860 genes related to 'RACE'.

Table S19.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  ASIAN 29
  BLACK OR AFRICAN AMERICAN 13
  WHITE 195
     
  Significant markers N = 860
List of top 10 genes differentially expressed by 'RACE'

Table S20.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

ANOVA_P Q
LOX|4015 1.996e-10 3.64e-06
DEGS1|8560 5.245e-10 9.57e-06
GPR176|11245 9.729e-10 1.78e-05
ALDH1L2|160428 1.09e-09 1.99e-05
ELOVL4|6785 1.106e-09 2.02e-05
CALU|813 1.16e-09 2.12e-05
CLIC4|25932 1.31e-09 2.39e-05
XKR9|389668 1.36e-09 2.48e-05
CTHRC1|115908 2.708e-09 4.94e-05
PALLD|23022 2.822e-09 5.15e-05
Clinical variable #12: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S21.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 4
  NOT HISPANIC OR LATINO 235
     
  Significant markers N = 0
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 = 256

  • Number of genes = 18247

  • 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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