Correlation between mRNAseq expression and clinical features
Kidney Renal Clear Cell Carcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1GB22XJ
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/C1GB22XJ
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 18273 genes and 11 clinical features across 519 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 7 clinical features related to at least one genes.

  • 51 genes correlated to 'AGE'.

    • RFPL1S|10740 ,  RANBP17|64901 ,  NEFH|4744 ,  WFDC1|58189 ,  UTY|7404 ,  ...

  • 2351 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • PLEKHA9|51054 ,  NR3C2|4306 ,  IL20RB|53833 ,  FAM122A|116224 ,  FKBP11|51303 ,  ...

  • 2671 genes correlated to 'PATHOLOGY.T.STAGE'.

    • NR3C2|4306 ,  ZNF132|7691 ,  PLEKHA9|51054 ,  FKBP11|51303 ,  ANKRD56|345079 ,  ...

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

    • RHBDF2|79651 ,  FAM64A|54478 ,  UBE2T|29089 ,  CDCA8|55143 ,  IQGAP3|128239 ,  ...

  • 1156 genes correlated to 'PATHOLOGY.M.STAGE'.

    • KIF20A|10112 ,  SKA1|220134 ,  ZNF668|79759 ,  GARNL3|84253 ,  PLEKHA9|51054 ,  ...

  • 542 genes correlated to 'GENDER'.

    • NCRNA00183|554203 ,  HDHD1A|8226 ,  DNAJB13|374407 ,  RAB42|115273 ,  RERG|85004 ,  ...

  • 121 genes correlated to 'RACE'.

    • TUBB8|347688 ,  LOC90784|90784 ,  NOTCH2NL|388677 ,  PWWP2B|170394 ,  DHX30|22907 ,  ...

  • No genes correlated to 'Time to Death', 'KARNOFSKY.PERFORMANCE.SCORE', '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=51 older N=8 younger N=43
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=2351        
PATHOLOGY T STAGE Spearman correlation test N=2671 higher stage N=1469 lower stage N=1202
PATHOLOGY N STAGE Wilcoxon test N=13 class1 N=13 class0 N=0
PATHOLOGY M STAGE Kruskal-Wallis test N=1156        
GENDER Wilcoxon test N=542 male N=542 female N=0
KARNOFSKY PERFORMANCE SCORE Spearman correlation test   N=0        
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
RACE Kruskal-Wallis test N=121        
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 (Years) 3-3668 (median=1307)
  censored N = 350
  death N = 23
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

51 genes related to 'AGE'.

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

AGE Mean (SD) 60.66 (12)
  Significant markers N = 51
  pos. correlated 8
  neg. correlated 43
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
RFPL1S|10740 -0.2673 8.219e-10 1.5e-05
RANBP17|64901 -0.2653 8.583e-10 1.57e-05
NEFH|4744 -0.2529 5.329e-09 9.74e-05
WFDC1|58189 -0.2499 8.153e-09 0.000149
UTY|7404 -0.2775 2.956e-08 0.00054
PALLD|23022 -0.2372 4.663e-08 0.000852
NKAPL|222698 -0.2269 1.843e-07 0.00337
NDUFAF2|91942 0.2253 2.195e-07 0.00401
MAPKAPK2|9261 0.2241 2.546e-07 0.00465
DIO2|1734 -0.2227 3.125e-07 0.00571
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

2351 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 256
  STAGE II 57
  STAGE III 125
  STAGE IV 81
     
  Significant markers N = 2351
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
PLEKHA9|51054 2.138e-18 3.91e-14
NR3C2|4306 4.419e-17 8.07e-13
IL20RB|53833 2.888e-16 5.28e-12
FAM122A|116224 1.229e-15 2.25e-11
FKBP11|51303 1.28e-15 2.34e-11
NOP2|4839 1.707e-15 3.12e-11
ZNF132|7691 2.387e-15 4.36e-11
TSPAN7|7102 7.31e-15 1.34e-10
TRIM36|55521 9.075e-15 1.66e-10
INHBE|83729 1.251e-14 2.29e-10
Clinical variable #4: 'PATHOLOGY.T.STAGE'

2671 genes related to 'PATHOLOGY.T.STAGE'.

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

PATHOLOGY.T.STAGE Mean (SD) 1.88 (0.96)
  N
  1 262
  2 69
  3 177
  4 11
     
  Significant markers N = 2671
  pos. correlated 1469
  neg. correlated 1202
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
NR3C2|4306 -0.3712 2.143e-18 3.92e-14
ZNF132|7691 -0.3681 4.229e-18 7.73e-14
PLEKHA9|51054 0.3625 1.454e-17 2.66e-13
FKBP11|51303 0.3525 1.248e-16 2.28e-12
ANKRD56|345079 -0.3413 1.423e-15 2.6e-11
TMEM150C|441027 -0.3401 1.6e-15 2.92e-11
TSPAN7|7102 -0.3388 2.084e-15 3.81e-11
FAM122A|116224 -0.3383 2.316e-15 4.23e-11
EMCN|51705 -0.3374 2.75e-15 5.02e-11
SHOX2|6474 0.3431 2.935e-15 5.36e-11
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

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

PATHOLOGY.N.STAGE Labels N
  class0 237
  class1 17
     
  Significant markers N = 13
  Higher in class1 13
  Higher in class0 0
List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S9.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'

W(pos if higher in 'class1') wilcoxontestP Q AUC
RHBDF2|79651 3433 1.259e-06 0.023 0.8521
FAM64A|54478 3350 4.021e-06 0.0734 0.835
UBE2T|29089 3348 5.222e-06 0.0954 0.831
CDCA8|55143 3332.5 6.71e-06 0.123 0.8271
IQGAP3|128239 3312 9.309e-06 0.17 0.822
FOXM1|2305 3302 1.09e-05 0.199 0.8196
CEP55|55165 3300 1.125e-05 0.205 0.8191
BIRC5|332 3292 1.275e-05 0.233 0.8171
SKA1|220134 3291 1.295e-05 0.237 0.8168
LMNB2|84823 3289 1.337e-05 0.244 0.8163
Clinical variable #6: 'PATHOLOGY.M.STAGE'

1156 genes related to 'PATHOLOGY.M.STAGE'.

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

PATHOLOGY.M.STAGE Labels N
  M0 421
  M1 79
  MX 18
     
  Significant markers N = 1156
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
KIF20A|10112 3.039e-11 5.55e-07
SKA1|220134 3.475e-11 6.35e-07
ZNF668|79759 4.096e-11 7.48e-07
GARNL3|84253 5.75e-11 1.05e-06
PLEKHA9|51054 1.006e-10 1.84e-06
TRIP13|9319 1.026e-10 1.87e-06
SKA3|221150 1.288e-10 2.35e-06
BIRC5|332 1.342e-10 2.45e-06
CCNB2|9133 1.409e-10 2.57e-06
IL20RB|53833 1.609e-10 2.94e-06
Clinical variable #7: 'GENDER'

542 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 184
  MALE 335
     
  Significant markers N = 542
  Higher in MALE 542
  Higher in FEMALE 0
List of top 10 genes differentially expressed by 'GENDER'

Table S13.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'. 59 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
NCRNA00183|554203 8218 1.701e-43 3.11e-39 0.8667
HDHD1A|8226 10253.5 2.597e-36 4.74e-32 0.8337
DNAJB13|374407 46095 3.404e-30 6.21e-26 0.8099
RAB42|115273 49402 5.938e-30 1.08e-25 0.8015
RERG|85004 47465 2.332e-24 4.26e-20 0.77
CYORF15A|246126 14516 3.408e-24 6.22e-20 0.9658
RNASET2|8635 46558 6.016e-22 1.1e-17 0.7553
CYORF15B|84663 13245 2.056e-21 3.75e-17 0.9499
CCDC146|57639 45815 4.53e-20 8.26e-16 0.7433
CDHR1|92211 45457 8.019e-20 1.46e-15 0.7419
Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

No gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.

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

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 90.75 (17)
  Score N
  0 1
  70 1
  80 4
  90 16
  100 18
     
  Significant markers N = 0
Clinical variable #9: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 30.2 (16)
  Significant markers N = 0
Clinical variable #10: 'RACE'

121 genes related to 'RACE'.

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

RACE Labels N
  ASIAN 8
  BLACK OR AFRICAN AMERICAN 42
  WHITE 462
     
  Significant markers N = 121
List of top 10 genes differentially expressed by 'RACE'

Table S17.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

ANOVA_P Q
TUBB8|347688 8.637e-12 1.58e-07
LOC90784|90784 1.098e-10 2.01e-06
NOTCH2NL|388677 8.431e-10 1.54e-05
PWWP2B|170394 1.725e-09 3.15e-05
DHX30|22907 4.135e-09 7.55e-05
FAM114A1|92689 2.148e-08 0.000392
ANKRD9|122416 5.294e-08 0.000967
MYOC|4653 6.923e-08 0.00126
GSTM2P1|442245 1.109e-07 0.00202
SLC10A7|84068 1.214e-07 0.00222
Clinical variable #11: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 26
  NOT HISPANIC OR LATINO 342
     
  Significant markers N = 0
Methods & Data
Input

  • Expresson data file = KIRC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt

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

  • Number of patients = 519

  • Number of genes = 18273

  • 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)
Copyright © 2015 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle