Correlation between mRNAseq expression and clinical features
Bladder Urothelial Carcinoma (Primary solid tumor)
15 January 2014  |  analyses__2014_01_15
Maintainer Information
Citation Information
doi:10.7908/C1PZ576D
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/C1PZ576D
Overview
Introduction

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

Summary

Testing the association between 18266 genes and 11 clinical features across 186 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.

  • 19 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • KLF9|687 ,  RGS1|5996 ,  TTC36|143941 ,  PXT1|222659 ,  SFRP2|6423 ,  ...

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

    • KLF9|687 ,  PCSK5|5125 ,  PTPRD|5789 ,  RRAGD|58528 ,  CTHRC1|115908 ,  ...

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

    • OCLN|4950 ,  GOLGA4|2803

  • 1 gene correlated to 'PATHOLOGY.M.STAGE'.

    • COX5A|9377

  • 16 genes correlated to 'GENDER'.

    • USP9Y|8287 ,  XIST|7503 ,  PRKY|5616 ,  TMSB4Y|9087 ,  CYORF15A|246126 ,  ...

  • 1 gene correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

    • LOC283070|283070

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

    • PRR15L|79170 ,  C6ORF141|135398 ,  OCLN|4950 ,  SLC44A2|57153

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

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=0        
NEOPLASM DISEASESTAGE ANOVA test N=19        
PATHOLOGY T STAGE Spearman correlation test N=9 higher stage N=9 lower stage N=0
PATHOLOGY N STAGE Spearman correlation test N=2 higher stage N=2 lower stage N=0
PATHOLOGY M STAGE ANOVA test N=1        
GENDER t test N=16 male N=11 female N=5
KARNOFSKY PERFORMANCE SCORE Spearman correlation test N=1 higher score N=0 lower score N=1
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
NUMBER OF LYMPH NODES Spearman correlation test N=4 higher number.of.lymph.nodes N=3 lower number.of.lymph.nodes N=1
GLEASON_SCORE Spearman correlation 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=7.6)
  censored N = 123
  death N = 56
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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

AGE Mean (SD) 67.74 (11)
  Significant markers N = 0
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

19 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S3.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 2
  STAGE II 59
  STAGE III 65
  STAGE IV 56
     
  Significant markers N = 19
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S4.  Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
KLF9|687 9.624e-10 1.76e-05
RGS1|5996 2.527e-08 0.000462
TTC36|143941 6.934e-08 0.00127
PXT1|222659 1.172e-07 0.00214
SFRP2|6423 1.211e-07 0.00221
LIMD1|8994 2.684e-07 0.0049
CTHRC1|115908 4.284e-07 0.00782
GAS1|2619 4.686e-07 0.00856
LARP6|55323 5.361e-07 0.00979
SLC41A2|84102 6.544e-07 0.0119

Figure S1.  Get High-res Image As an example, this figure shows the association of KLF9|687 to 'NEOPLASM.DISEASESTAGE'. P value = 9.62e-10 with ANOVA analysis.

Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.83 (0.72)
  N
  0 1
  1 1
  2 51
  3 88
  4 27
     
  Significant markers N = 9
  pos. correlated 9
  neg. correlated 0
List of 9 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

Table S6.  Get Full Table List of 9 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
KLF9|687 0.4119 2.906e-08 0.000531
PCSK5|5125 0.3744 6.231e-07 0.0114
PTPRD|5789 0.3653 1.299e-06 0.0237
RRAGD|58528 0.3601 1.632e-06 0.0298
CTHRC1|115908 0.36 1.638e-06 0.0299
SLC46A3|283537 0.3592 1.734e-06 0.0317
GEM|2669 0.3585 1.831e-06 0.0334
IGF1|3479 0.3574 1.978e-06 0.0361
CRISPLD2|83716 0.353 2.683e-06 0.049

Figure S2.  Get High-res Image As an example, this figure shows the association of KLF9|687 to 'PATHOLOGY.T.STAGE'. P value = 2.91e-08 with Spearman correlation analysis.

Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.59 (0.92)
  N
  0 114
  1 17
  2 33
  3 6
     
  Significant markers N = 2
  pos. correlated 2
  neg. correlated 0
List of 2 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

Table S8.  Get Full Table List of 2 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
OCLN|4950 0.3663 8.96e-07 0.0164
GOLGA4|2803 0.3627 1.166e-06 0.0213

Figure S3.  Get High-res Image As an example, this figure shows the association of OCLN|4950 to 'PATHOLOGY.N.STAGE'. P value = 8.96e-07 with Spearman correlation analysis.

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

One gene related to 'PATHOLOGY.M.STAGE'.

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

PATHOLOGY.M.STAGE Labels N
  M0 100
  M1 5
  MX 80
     
  Significant markers N = 1
List of one gene differentially expressed by 'PATHOLOGY.M.STAGE'

Table S10.  Get Full Table List of one gene differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
COX5A|9377 1.205e-07 0.0022

Figure S4.  Get High-res Image As an example, this figure shows the association of COX5A|9377 to 'PATHOLOGY.M.STAGE'. P value = 1.2e-07 with ANOVA analysis.

Clinical variable #7: 'GENDER'

16 genes related to 'GENDER'.

Table S11.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 47
  MALE 139
     
  Significant markers N = 16
  Higher in MALE 11
  Higher in FEMALE 5
List of top 10 genes differentially expressed by 'GENDER'

Table S12.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
USP9Y|8287 45.99 5.371e-76 9.8e-72 1
XIST|7503 -27.17 1.029e-51 1.88e-47 0.9947
PRKY|5616 29.52 3.865e-51 7.06e-47 0.9988
TMSB4Y|9087 27.31 2.686e-50 4.9e-46 0.985
CYORF15A|246126 37.78 2.631e-45 4.8e-41 1
ZFY|7544 34.18 6.174e-38 1.13e-33 0.9993
RPS4Y1|6192 40.25 3.274e-35 5.98e-31 1
TSIX|9383 -19.91 3.503e-32 6.39e-28 0.9921
DDX3Y|8653 37.74 2.277e-31 4.15e-27 1
NLGN4Y|22829 21.2 2.647e-27 4.83e-23 0.987

Figure S5.  Get High-res Image As an example, this figure shows the association of USP9Y|8287 to 'GENDER'. P value = 5.37e-76 with T-test analysis.

Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

One gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S13.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 77.8 (16)
  Significant markers N = 1
  pos. correlated 0
  neg. correlated 1
List of one gene significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

Table S14.  Get Full Table List of one gene significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

SpearmanCorr corrP Q
LOC283070|283070 -0.6841 4.338e-08 0.000792

Figure S6.  Get High-res Image As an example, this figure shows the association of LOC283070|283070 to 'KARNOFSKY.PERFORMANCE.SCORE'. P value = 4.34e-08 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #9: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

Table S15.  Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED Mean (SD) 38.19 (26)
  Significant markers N = 0
Clinical variable #10: 'NUMBER.OF.LYMPH.NODES'

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

Table S16.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 1.58 (3.4)
  Significant markers N = 4
  pos. correlated 3
  neg. correlated 1
List of 4 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

Table S17.  Get Full Table List of 4 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
PRR15L|79170 0.424 3.317e-07 0.00606
C6ORF141|135398 -0.4354 3.486e-07 0.00637
OCLN|4950 0.4099 8.725e-07 0.0159
SLC44A2|57153 0.3948 2.352e-06 0.043

Figure S7.  Get High-res Image As an example, this figure shows the association of PRR15L|79170 to 'NUMBER.OF.LYMPH.NODES'. P value = 3.32e-07 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #11: 'GLEASON_SCORE'

No gene related to 'GLEASON_SCORE'.

Table S18.  Basic characteristics of clinical feature: 'GLEASON_SCORE'

GLEASON_SCORE Mean (SD) 6.44 (0.68)
  Score N
  6 25
  7 12
  8 1
  9 1
     
  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 = 186

  • Number of genes = 18266

  • 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)
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