Correlation between mRNAseq expression and clinical features
Kidney Renal Clear Cell 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/C15H7F18
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 18274 genes and 11 clinical features across 507 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 7 clinical features related to at least one genes.

  • 50 genes correlated to 'AGE'.

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

  • 2483 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • PLEKHA9|51054 ,  NR3C2|4306 ,  FAM122A|116224 ,  NOP2|4839 ,  IL20RB|53833 ,  ...

  • 2779 genes correlated to 'PATHOLOGY.T.STAGE'.

    • NR3C2|4306 ,  ZNF132|7691 ,  PLEKHA9|51054 ,  FKBP11|51303 ,  FAM122A|116224 ,  ...

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

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

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

    • PLEKHA9|51054 ,  IL20RB|53833 ,  GARNL3|84253 ,  KIF20A|10112 ,  TRIP13|9319 ,  ...

  • 485 genes correlated to 'GENDER'.

    • NCRNA00183|554203 ,  HDHD1A|8226 ,  RAB42|115273 ,  DNAJB13|374407 ,  CYORF15A|246126 ,  ...

  • 23 genes correlated to 'RACE'.

    • LOC90784|90784 ,  APLN|8862 ,  TUBB8|347688 ,  NOTCH2NL|388677 ,  DOK7|285489 ,  ...

  • 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=50 older N=9 younger N=41
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=2483        
PATHOLOGY T STAGE Spearman correlation test N=2779 higher stage N=1536 lower stage N=1243
PATHOLOGY N STAGE Wilcoxon test N=15 class1 N=15 class0 N=0
PATHOLOGY M STAGE Kruskal-Wallis test N=600        
GENDER Wilcoxon test N=485 male N=485 female N=0
KARNOFSKY PERFORMANCE SCORE Spearman correlation test   N=0        
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
RACE Kruskal-Wallis test N=23        
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) 7-3668 (median=1311)
  censored N = 341
  death N = 25
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

50 genes related to 'AGE'.

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

AGE Mean (SD) 60.62 (12)
  Significant markers N = 50
  pos. correlated 9
  neg. correlated 41
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
RANBP17|64901 -0.2738 3.728e-10 6.81e-06
RFPL1S|10740 -0.2687 1.061e-09 1.94e-05
WFDC1|58189 -0.2592 3.283e-09 6e-05
NEFH|4744 -0.2506 1.107e-08 0.000202
UTY|7404 -0.2773 3.443e-08 0.000629
PALLD|23022 -0.2388 5.443e-08 0.000994
DIO2|1734 -0.2268 2.595e-07 0.00474
NKAPL|222698 -0.2235 3.877e-07 0.00708
MAPKAPK2|9261 0.2232 3.937e-07 0.00719
NDUFAF2|91942 0.2208 5.26e-07 0.00961
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

2483 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 246
  STAGE II 56
  STAGE III 125
  STAGE IV 80
     
  Significant markers N = 2483
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 2.693e-18 4.92e-14
NR3C2|4306 2.792e-17 5.1e-13
FAM122A|116224 4.644e-16 8.49e-12
NOP2|4839 5.188e-16 9.48e-12
IL20RB|53833 5.857e-16 1.07e-11
FKBP11|51303 1.788e-15 3.27e-11
TSPAN7|7102 2.133e-15 3.9e-11
INHBE|83729 3.055e-15 5.58e-11
ZNF132|7691 5.432e-15 9.92e-11
TRIM36|55521 1.521e-14 2.78e-10
Clinical variable #4: 'PATHOLOGY.T.STAGE'

2779 genes related to 'PATHOLOGY.T.STAGE'.

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

PATHOLOGY.T.STAGE Mean (SD) 1.9 (0.96)
  N
  1 252
  2 67
  3 177
  4 11
     
  Significant markers N = 2779
  pos. correlated 1536
  neg. correlated 1243
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 -0.3763 1.679e-18 3.07e-14
ZNF132|7691 -0.3696 7.373e-18 1.35e-13
PLEKHA9|51054 0.3668 1.368e-17 2.5e-13
FKBP11|51303 0.3534 2.307e-16 4.22e-12
FAM122A|116224 -0.3488 5.939e-16 1.08e-11
TMEM150C|441027 -0.3469 8.737e-16 1.6e-11
ANKRD56|345079 -0.3456 1.228e-15 2.24e-11
TSPAN7|7102 -0.3446 1.395e-15 2.55e-11
NOP2|4839 0.3441 1.554e-15 2.84e-11
FAM160A1|729830 -0.3419 2.376e-15 4.34e-11
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

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

PATHOLOGY.N.STAGE Labels N
  class0 236
  class1 17
     
  Significant markers N = 15
  Higher in class1 15
  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 9.824e-07 0.0179 0.8557
FAM64A|54478 3343 3.58e-06 0.0654 0.8368
UBE2T|29089 3346 4.295e-06 0.0784 0.834
CDCA8|55143 3330.5 5.535e-06 0.101 0.8301
IQGAP3|128239 3309 7.836e-06 0.143 0.8248
FOXM1|2305 3298 9.342e-06 0.171 0.822
CEP55|55165 3297 9.491e-06 0.173 0.8218
BIRC5|332 3292 1.028e-05 0.188 0.8205
SKA1|220134 3290 1.061e-05 0.194 0.82
LMNB2|84823 3285 1.148e-05 0.21 0.8188
Clinical variable #6: 'PATHOLOGY.M.STAGE'

600 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 7
     
  Significant markers N = 600
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
PLEKHA9|51054 6.971e-11 1.27e-06
IL20RB|53833 2.213e-10 4.04e-06
GARNL3|84253 2.888e-10 5.28e-06
KIF20A|10112 3.374e-10 6.16e-06
TRIP13|9319 4.679e-10 8.55e-06
SKA1|220134 4.866e-10 8.89e-06
BIRC5|332 5.514e-10 1.01e-05
INHBE|83729 5.669e-10 1.04e-05
C22ORF9|23313 8.496e-10 1.55e-05
IGF2BP3|10643 9.038e-10 1.65e-05
Clinical variable #7: 'GENDER'

485 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 174
  MALE 333
     
  Significant markers N = 485
  Higher in MALE 485
  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'. 57 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
NCRNA00183|554203 7767 9.27e-42 1.69e-37 0.866
HDHD1A|8226 9719.5 1.003e-34 1.83e-30 0.8323
RAB42|115273 46909 2.268e-30 4.14e-26 0.8096
DNAJB13|374407 43011 1.602e-28 2.93e-24 0.8069
CYORF15A|246126 14429 3.544e-24 6.47e-20 0.9658
RERG|85004 44191 2.535e-22 4.63e-18 0.7627
CYORF15B|84663 13164 2.16e-21 3.94e-17 0.9498
RNASET2|8635 43756 3.73e-21 6.81e-17 0.7552
CCDC146|57639 43197 1.056e-19 1.93e-15 0.7455
CDHR1|92211 42702 4.563e-19 8.32e-15 0.7414
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) 90.86 (18)
  Score N
  0 1
  70 1
  80 3
  90 13
  100 17
     
  Significant markers N = 0
Clinical variable #9: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 29 (15)
  Value N
  7 1
  10 1
  30 2
  40 2
  46 1
     
  Significant markers N = 0
Clinical variable #10: 'RACE'

23 genes related to 'RACE'.

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

RACE Labels N
  ASIAN 8
  BLACK OR AFRICAN AMERICAN 30
  WHITE 462
     
  Significant markers N = 23
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
LOC90784|90784 2.918e-09 5.33e-05
APLN|8862 2.827e-07 0.00516
TUBB8|347688 4.361e-07 0.00797
NOTCH2NL|388677 7.581e-07 0.0139
DOK7|285489 3.737e-06 0.0683
MYOC|4653 4.218e-06 0.0771
NKAIN1|79570 4.53e-06 0.0827
RALGPS1|9649 5.454e-06 0.0996
DHX30|22907 6.68e-06 0.122
SCEL|8796 6.777e-06 0.124
Clinical variable #11: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 24
  NOT HISPANIC OR LATINO 332
     
  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 = 507

  • Number of genes = 18274

  • 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)