Correlation between mRNAseq expression and clinical features
Kidney Renal Clear Cell Carcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1M32TSP
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1M32TSP
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 18278 genes and 12 clinical features across 529 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 8 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

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

  • 30 genes correlated to 'NEOPLASM_DISEASESTAGE'.

    • PLEKHA9|51054 ,  NR3C2|4306 ,  IL20RB|53833 ,  ZNF132|7691 ,  FKBP11|51303 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

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

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

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

  • 30 genes correlated to 'PATHOLOGY_M_STAGE'.

    • PLEKHA9|51054 ,  IL20RB|53833 ,  GARNL3|84253 ,  INHBE|83729 ,  C22ORF9|23313 ,  ...

  • 9 genes correlated to 'GENDER'.

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

  • 2 genes correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

    • ZNF410|57862 ,  TAF1A|9015

  • 30 genes correlated to 'RACE'.

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

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'NUMBER_PACK_YEARS_SMOKED', 'YEAR_OF_TOBACCO_SMOKING_ONSET', 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
DAYS_TO_DEATH_OR_LAST_FUP Cox regression test   N=0        
YEARS_TO_BIRTH Spearman correlation test N=30 older N=5 younger N=25
NEOPLASM_DISEASESTAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=13 lower stage N=17
PATHOLOGY_N_STAGE Wilcoxon test N=30 n1 N=30 n0 N=0
PATHOLOGY_M_STAGE Wilcoxon test N=30 class1 N=30 class0 N=0
GENDER Wilcoxon test N=9 male N=9 female N=0
KARNOFSKY_PERFORMANCE_SCORE Spearman correlation test N=2 higher score N=2 lower score N=0
NUMBER_PACK_YEARS_SMOKED Spearman correlation test   N=0        
YEAR_OF_TOBACCO_SMOKING_ONSET Spearman correlation test   N=0        
RACE Kruskal-Wallis test N=30        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

No gene related to 'DAYS_TO_DEATH_OR_LAST_FUP'.

Table S1.  Basic characteristics of clinical feature: 'DAYS_TO_DEATH_OR_LAST_FUP'

DAYS_TO_DEATH_OR_LAST_FUP Duration (Months) 0.1-120.6 (median=36.4)
  censored N = 360
  death N = 168
     
  Significant markers N = 0
Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 60.67 (12)
  Significant markers N = 30
  pos. correlated 5
  neg. correlated 25
List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

Table S3.  Get Full Table List of top 10 genes significantly correlated to 'YEARS_TO_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
RANBP17|64901 -0.2667 4.783e-10 6.46e-06
RFPL1S|10740 -0.2658 7.066e-10 6.46e-06
WFDC1|58189 -0.2554 2.628e-09 1.37e-05
NEFH|4744 -0.2545 2.993e-09 1.37e-05
UTY|7404 -0.2879 5.872e-09 2.15e-05
PALLD|23022 -0.2395 2.516e-08 7.66e-05
NDUFAF2|91942 0.23 9.071e-08 0.000237
KDM5D|8284 -0.2539 1.159e-07 0.000265
USP9Y|8287 -0.2542 1.584e-07 0.000292
ZFY|7544 -0.244 1.599e-07 0.000292
Clinical variable #3: 'NEOPLASM_DISEASESTAGE'

30 genes related to 'NEOPLASM_DISEASESTAGE'.

Table S4.  Basic characteristics of clinical feature: 'NEOPLASM_DISEASESTAGE'

NEOPLASM_DISEASESTAGE Labels N
  STAGE I 265
  STAGE II 57
  STAGE III 126
  STAGE IV 81
     
  Significant markers N = 30
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'

kruskal_wallis_P Q
PLEKHA9|51054 5.87e-19 1.07e-14
NR3C2|4306 7.129e-17 6.51e-13
IL20RB|53833 2.568e-16 1.56e-12
ZNF132|7691 1.441e-15 6.1e-12
FKBP11|51303 1.84e-15 6.1e-12
NOP2|4839 2.002e-15 6.1e-12
TSPAN7|7102 2.87e-15 6.9e-12
TRIM36|55521 3.021e-15 6.9e-12
NFE2L3|9603 4.683e-15 9.51e-12
INHBE|83729 5.682e-15 1.04e-11
Clinical variable #4: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'

PATHOLOGY_T_STAGE Mean (SD) 1.87 (0.96)
  N
  T1 270
  T2 69
  T3 179
  T4 11
     
  Significant markers N = 30
  pos. correlated 13
  neg. correlated 17
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
PLEKHA9|51054 0.3673 2.447e-18 2.54e-14
ZNF132|7691 -0.366 3.241e-18 2.54e-14
NR3C2|4306 -0.3649 4.161e-18 2.54e-14
FKBP11|51303 0.3496 1.184e-16 5.41e-13
ANKRD56|345079 -0.3398 1.043e-15 3.72e-12
TSPAN7|7102 -0.3384 1.222e-15 3.72e-12
TMEM150C|441027 -0.3373 1.544e-15 3.72e-12
SHOX2|6474 0.3435 1.629e-15 3.72e-12
TRIM36|55521 0.3356 2.147e-15 4.13e-12
CAPZA1|829 0.3354 2.257e-15 4.13e-12
Clinical variable #5: 'PATHOLOGY_N_STAGE'

30 genes related to 'PATHOLOGY_N_STAGE'.

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY_N_STAGE'

PATHOLOGY_N_STAGE Labels N
  N0 238
  N1 17
     
  Significant markers N = 30
  Higher in N1 30
  Higher in N0 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 'N1') wilcoxontestP Q AUC
RHBDF2|79651 3449 1.222e-06 0.0177 0.8524
FAM64A|54478 3365 3.954e-06 0.0177 0.8352
UBE2T|29089 3364 5.049e-06 0.0177 0.8314
CDCA8|55143 3348.5 6.484e-06 0.0177 0.8276
IQGAP3|128239 3328 8.988e-06 0.0177 0.8225
CEP55|55165 3317 1.069e-05 0.0177 0.8198
FOXM1|2305 3317 1.069e-05 0.0177 0.8198
BIRC5|332 3306 1.269e-05 0.0177 0.8171
SKA1|220134 3306 1.269e-05 0.0177 0.8171
PI3|5266 2766 1.316e-05 0.0177 0.8272
Clinical variable #6: 'PATHOLOGY_M_STAGE'

30 genes related to 'PATHOLOGY_M_STAGE'.

Table S10.  Basic characteristics of clinical feature: 'PATHOLOGY_M_STAGE'

PATHOLOGY_M_STAGE Labels N
  class0 422
  class1 79
     
  Significant markers N = 30
  Higher in class1 30
  Higher in class0 0
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'

W(pos if higher in 'class1') wilcoxontestP Q AUC
PLEKHA9|51054 24695 1.077e-11 1.97e-07 0.7407
IL20RB|53833 24533.5 2.756e-11 2.16e-07 0.7359
GARNL3|84253 8848 3.538e-11 2.16e-07 0.7346
INHBE|83729 24223 8.508e-11 3.34e-07 0.73
C22ORF9|23313 24266 1.255e-10 3.34e-07 0.7279
SKA1|220134 24215 1.666e-10 3.34e-07 0.7263
BIRC5|332 24208 1.732e-10 3.34e-07 0.7261
ENPP5|59084 9133 1.761e-10 3.34e-07 0.726
UBE2C|11065 24184 1.977e-10 3.34e-07 0.7254
GTSE1|51512 24127 1.989e-10 3.34e-07 0.7254
Clinical variable #7: 'GENDER'

9 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 187
  MALE 342
     
  Significant markers N = 9
  Higher in MALE 9
  Higher in FEMALE 0
List of 9 genes differentially expressed by 'GENDER'

Table S13.  Get Full Table List of 9 genes differentially expressed by 'GENDER'. 21 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
NCRNA00183|554203 8378 8.726e-45 1.77e-41 0.869
HDHD1A|8226 10693.5 9.428e-37 1.33e-33 0.8328
DNAJB13|374407 48066 2.777e-31 2.99e-28 0.8128
RAB42|115273 51279 1.58e-30 1.6e-27 0.8018
RERG|85004 49222 1.061e-24 8.08e-22 0.7696
CYORF15A|246126 14820 3.004e-24 2.2e-21 0.9658
RNASET2|8635 48514 7.627e-23 5.16e-20 0.7586
CYORF15B|84663 13528 1.749e-21 1.1e-18 0.9501
CCDC146|57639 47689 8.9e-21 5.42e-18 0.7457
Clinical variable #8: 'KARNOFSKY_PERFORMANCE_SCORE'

2 genes related to 'KARNOFSKY_PERFORMANCE_SCORE'.

Table S14.  Basic characteristics of clinical feature: 'KARNOFSKY_PERFORMANCE_SCORE'

KARNOFSKY_PERFORMANCE_SCORE Mean (SD) 90.23 (17)
  Significant markers N = 2
  pos. correlated 2
  neg. correlated 0
List of 2 genes differentially expressed by 'KARNOFSKY_PERFORMANCE_SCORE'

Table S15.  Get Full Table List of 2 genes significantly correlated to 'KARNOFSKY_PERFORMANCE_SCORE' by Spearman correlation test

SpearmanCorr corrP Q
ZNF410|57862 0.5919 2.907e-05 0.295
TAF1A|9015 0.5892 3.227e-05 0.295
Clinical variable #9: 'NUMBER_PACK_YEARS_SMOKED'

No gene related to 'NUMBER_PACK_YEARS_SMOKED'.

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

NUMBER_PACK_YEARS_SMOKED Mean (SD) 28.93 (18)
  Significant markers N = 0
Clinical variable #10: 'YEAR_OF_TOBACCO_SMOKING_ONSET'

No gene related to 'YEAR_OF_TOBACCO_SMOKING_ONSET'.

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

YEAR_OF_TOBACCO_SMOKING_ONSET Mean (SD) 1979.62 (21)
  Significant markers N = 0
Clinical variable #11: 'RACE'

30 genes related to 'RACE'.

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

RACE Labels N
  ASIAN 8
  BLACK OR AFRICAN AMERICAN 52
  WHITE 462
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S19.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
TUBB8|347688 1.035e-13 1.89e-09
LOC90784|90784 4.769e-13 4.36e-09
PWWP2B|170394 7.312e-12 4.45e-08
DHX30|22907 1.443e-11 6.6e-08
NOTCH2NL|388677 2.615e-11 9.56e-08
NACA2|342538 2.845e-10 8.67e-07
ANKRD9|122416 3.425e-10 8.94e-07
ZNF775|285971 4.116e-10 9.11e-07
FAM114A1|92689 4.485e-10 9.11e-07
FTHL3|2498 5.662e-10 1.03e-06
Clinical variable #12: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 26
  NOT HISPANIC OR LATINO 350
     
  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 = 529

  • Number of genes = 18278

  • Number of clinical features = 12

Selected clinical features

  • For clinical features selected for this analysis and their value conozzle.versions, please find a documentation on selected CDEs .

  • Survival time data

    • Survival time data is a combined value of days_to_death and days_to_last_followup. For each patient, it creates a combined value 'days_to_death_or_last_fup' using conversion process below.

      • if 'vital_status'==1(dead), 'days_to_last_followup' is always NA. Thus, uses 'days_to_death' value for 'days_to_death_or_fup'

      • if 'vital_status'==0(alive),

        • if 'days_to_death'==NA & 'days_to_last_followup'!=NA, uses 'days_to_last_followup' value for 'days_to_death_or_fup'

        • if 'days_to_death'!=NA, excludes this case in survival analysis and report the case.

      • if 'vital_status'==NA,excludes this case in survival analysis and report the case.

    • cf. In certain diesase types such as SKCM, days_to_death parameter is replaced with time_from_specimen_dx or time_from_specimen_procurement_to_death .

  • This analysis excluded clinical variables that has only NA values.

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

Wilcoxon rank sum test (Mann-Whitney U test)

For two groups (mutant or wild-type) of continuous type of clinical data, wilcoxon rank sum test (Mann and Whitney, 1947) was applied to compare their mean difference using 'wilcox.test(continuous.clinical ~ as.factor(group), exact=FALSE)' function in R. This test is equivalent to the Mann-Whitney test.

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] Mann and Whitney, On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other, Annals of Mathematical Statistics 18 (1), 50-60 (1947)
[4] 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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