Correlation between mRNAseq expression and clinical features
Pan-kidney cohort (KICH+KIRC+KIRP) (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
doi:10.7908/C1Q23ZG8
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/C1Q23ZG8
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 18216 genes and 14 clinical features across 888 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 11 clinical features related to at least one genes.

  • 30 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • ACAT1|38 ,  ACSS3|79611 ,  AKAP6|9472 ,  ANK3|288 ,  ANKRD56|345079 ,  ...

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • KIT|3815 ,  CYTSB|92521 ,  NRXN3|9369 ,  MEX3C|51320 ,  ZC3H4|23211 ,  ...

  • 30 genes correlated to 'PATHOLOGIC_STAGE'.

    • KIF20A|10112 ,  NCAPG|64151 ,  UBE2C|11065 ,  CEP55|55165 ,  SKA1|220134 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • UBE2C|11065 ,  BUB1|699 ,  NCAPG|64151 ,  CCNB2|9133 ,  TPX2|22974 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • UBE2T|29089 ,  PKMYT1|9088 ,  C16ORF59|80178 ,  FASN|2194 ,  BIRC5|332 ,  ...

  • 30 genes correlated to 'PATHOLOGY_M_STAGE'.

    • NCAPG|64151 ,  CEP55|55165 ,  BIRC5|332 ,  PTTG1|9232 ,  SKA1|220134 ,  ...

  • 7 genes correlated to 'GENDER'.

    • NCRNA00183|554203 ,  HDHD1A|8226 ,  DNAJB13|374407 ,  CYORF15A|246126 ,  CCDC146|57639 ,  ...

  • 30 genes correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

    • PTGR2|145482 ,  CYP1B1|1545 ,  PHF7|51533 ,  SAPS2|9701 ,  PATZ1|23598 ,  ...

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • NDUFA4L2|56901 ,  ELTD1|64123 ,  GPR4|2828 ,  FLT1|2321 ,  CDH13|1012 ,  ...

  • 21 genes correlated to 'YEAR_OF_TOBACCO_SMOKING_ONSET'.

    • AGK|55750 ,  POM121|9883 ,  CD1B|910 ,  PPAPDC1B|84513 ,  NOM1|64434 ,  ...

  • 30 genes correlated to 'RACE'.

    • NOTCH2NL|388677 ,  TUBB8|347688 ,  LOC90784|90784 ,  ULK4|54986 ,  CROCCL1|84809 ,  ...

  • No genes correlated to 'RADIATION_THERAPY', 'NUMBER_PACK_YEARS_SMOKED', 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=30 shorter survival N=21 longer survival N=9
YEARS_TO_BIRTH Spearman correlation test N=30 older N=9 younger N=21
PATHOLOGIC_STAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=28 lower stage N=2
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=30 lower stage N=0
PATHOLOGY_M_STAGE Wilcoxon test N=30 class1 N=30 class0 N=0
GENDER Wilcoxon test N=7 male N=7 female N=0
RADIATION_THERAPY Wilcoxon test   N=0        
KARNOFSKY_PERFORMANCE_SCORE Spearman correlation test N=30 higher score N=18 lower score N=12
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
NUMBER_PACK_YEARS_SMOKED Spearman correlation test   N=0        
YEAR_OF_TOBACCO_SMOKING_ONSET Spearman correlation test N=21 higher year_of_tobacco_smoking_onset N=6 lower year_of_tobacco_smoking_onset N=15
RACE Kruskal-Wallis test N=30        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

30 genes 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) 0.1-194.8 (median=34.9)
  censored N = 659
  death N = 228
     
  Significant markers N = 30
  associated with shorter survival 21
  associated with longer survival 9
List of top 10 genes differentially expressed by 'DAYS_TO_DEATH_OR_LAST_FUP'

Table S2.  Get Full Table List of top 10 genes significantly associated with 'Time to Death' by Cox regression test

HazardRatio Wald_P Q C_index
ACAT1|38 0.61 0 0 0.319
ACSS3|79611 0.77 0 0 0.332
AKAP6|9472 0.66 0 0 0.352
ANK3|288 0.71 0 0 0.352
ANKRD56|345079 0.7 0 0 0.333
ANLN|54443 1.61 0 0 0.685
ARHGAP11A|9824 1.75 0 0 0.661
ARHGAP24|83478 0.59 0 0 0.349
ASPM|259266 1.56 0 0 0.707
AUH|549 0.51 0 0 0.321
Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

Table S3.  Basic characteristics of clinical feature: 'YEARS_TO_BIRTH'

YEARS_TO_BIRTH Mean (SD) 60.18 (13)
  Significant markers N = 30
  pos. correlated 9
  neg. correlated 21
List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

Table S4.  Get Full Table List of top 10 genes significantly correlated to 'YEARS_TO_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
KIT|3815 -0.2226 2.305e-11 4.2e-07
CYTSB|92521 -0.2137 1.449e-10 1.07e-06
NRXN3|9369 -0.2128 1.769e-10 1.07e-06
MEX3C|51320 -0.2104 2.8e-10 1.25e-06
ZC3H4|23211 -0.209 3.648e-10 1.25e-06
VKORC1|79001 0.2084 4.102e-10 1.25e-06
ZMIZ1|57178 -0.2068 5.61e-10 1.46e-06
NKAPL|222698 -0.2046 9.852e-10 2.24e-06
DACT1|51339 -0.2004 1.912e-09 3.52e-06
BACH2|60468 -0.2004 1.933e-09 3.52e-06
Clinical variable #3: 'PATHOLOGIC_STAGE'

30 genes related to 'PATHOLOGIC_STAGE'.

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGIC_STAGE'

PATHOLOGIC_STAGE Labels N
  STAGE I 461
  STAGE II 104
  STAGE III 190
  STAGE IV 105
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'PATHOLOGIC_STAGE'

Table S6.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGIC_STAGE'

kruskal_wallis_P Q
KIF20A|10112 5.5e-35 1e-30
NCAPG|64151 3.212e-33 2.43e-29
UBE2C|11065 4.852e-33 2.43e-29
CEP55|55165 5.333e-33 2.43e-29
SKA1|220134 6.98e-33 2.54e-29
TPX2|22974 2.704e-32 8.21e-29
BIRC5|332 5.71e-32 1.49e-28
HJURP|55355 1.506e-31 3.43e-28
PTTG1|9232 3.077e-31 6.23e-28
CCNB2|9133 3.624e-31 6.6e-28
Clinical variable #4: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'

PATHOLOGY_T_STAGE Mean (SD) 1.78 (0.93)
  N
  T1 486
  T2 127
  T3 258
  T4 15
     
  Significant markers N = 30
  pos. correlated 28
  neg. correlated 2
List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S8.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
UBE2C|11065 0.3908 1.033e-33 1.88e-29
BUB1|699 0.3877 3.994e-33 3.64e-29
NCAPG|64151 0.3822 3.625e-32 2.2e-28
CCNB2|9133 0.3795 9.808e-32 4.47e-28
TPX2|22974 0.3749 5.977e-31 2.18e-27
GTSE1|51512 0.3736 1.076e-30 3.23e-27
KIF20A|10112 0.3734 1.24e-30 3.23e-27
SKA1|220134 0.3724 1.588e-30 3.62e-27
CENPF|1063 0.3666 1.414e-29 2.86e-26
CEP55|55165 0.3663 1.598e-29 2.91e-26
Clinical variable #5: 'PATHOLOGY_N_STAGE'

30 genes related to 'PATHOLOGY_N_STAGE'.

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY_N_STAGE'

PATHOLOGY_N_STAGE Mean (SD) 0.15 (0.41)
  N
  N0 329
  N1 43
  N2 7
     
  Significant markers N = 30
  pos. correlated 30
  neg. correlated 0
List of top 10 genes differentially expressed by 'PATHOLOGY_N_STAGE'

Table S10.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_N_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
UBE2T|29089 0.4388 2.893e-19 5.27e-15
PKMYT1|9088 0.4266 3.795e-18 3.46e-14
C16ORF59|80178 0.4039 2.867e-16 1.74e-12
FASN|2194 0.3909 2.76e-15 1.26e-11
BIRC5|332 0.3892 3.7e-15 1.35e-11
NEK2|4751 0.3849 7.802e-15 2.37e-11
CDC20|991 0.3829 1.112e-14 2.86e-11
AURKB|9212 0.3822 1.258e-14 2.86e-11
PLK1|5347 0.3807 1.619e-14 3.28e-11
PYCR1|5831 0.3797 1.904e-14 3.47e-11
Clinical variable #6: 'PATHOLOGY_M_STAGE'

30 genes related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 550
  class1 90
     
  Significant markers N = 30
  Higher in class1 30
  Higher in class0 0
List of top 10 genes differentially expressed by 'PATHOLOGY_M_STAGE'

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

W(pos if higher in 'class1') wilcoxontestP Q AUC
NCAPG|64151 37376 5.938e-15 6.36e-11 0.7564
CEP55|55165 37373 8.324e-15 6.36e-11 0.755
BIRC5|332 37224 1.242e-14 6.36e-11 0.7534
PTTG1|9232 37169 2.222e-14 6.36e-11 0.7509
SKA1|220134 37163 2.286e-14 6.36e-11 0.7508
CENPA|1058 37083 2.445e-14 6.36e-11 0.7505
OIP5|11339 37017 2.446e-14 6.36e-11 0.7505
IGF2BP3|10643 37064 3.66e-14 8.33e-11 0.7488
CCNB2|9133 36961 5.95e-14 1.15e-10 0.7467
KIF18B|146909 36948 6.324e-14 1.15e-10 0.7464
Clinical variable #7: 'GENDER'

7 genes related to 'GENDER'.

Table S13.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 291
  MALE 597
     
  Significant markers N = 7
  Higher in MALE 7
  Higher in FEMALE 0
List of 7 genes differentially expressed by 'GENDER'

Table S14.  Get Full Table List of 7 genes differentially expressed by 'GENDER'. 23 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
NCRNA00183|554203 28737 4.858e-59 8.85e-56 0.8346
HDHD1A|8226 37763.5 1.227e-42 1.49e-39 0.7826
DNAJB13|374407 119080.5 1.057e-35 9.63e-33 0.7655
CYORF15A|246126 34096 7.153e-30 5.21e-27 0.941
CCDC146|57639 126637 1.459e-28 1.02e-25 0.7289
PROM1|8842 122890.5 1.668e-28 1.13e-25 0.731
RERG|85004 126172 6.158e-28 4.01e-25 0.7263
Clinical variable #8: 'RADIATION_THERAPY'

No gene related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 406
  YES 3
     
  Significant markers N = 0
Clinical variable #9: 'KARNOFSKY_PERFORMANCE_SCORE'

30 genes related to 'KARNOFSKY_PERFORMANCE_SCORE'.

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

KARNOFSKY_PERFORMANCE_SCORE Mean (SD) 88.31 (22)
  Significant markers N = 30
  pos. correlated 18
  neg. correlated 12
List of top 10 genes differentially expressed by 'KARNOFSKY_PERFORMANCE_SCORE'

Table S17.  Get Full Table List of top 10 genes significantly correlated to 'KARNOFSKY_PERFORMANCE_SCORE' by Spearman correlation test

SpearmanCorr corrP Q
PTGR2|145482 0.3736 4.661e-06 0.0849
CYP1B1|1545 -0.3517 1.772e-05 0.118
PHF7|51533 0.3501 1.94e-05 0.118
SAPS2|9701 0.34 3.471e-05 0.118
PATZ1|23598 0.3385 3.791e-05 0.118
CIRBP|1153 0.3328 5.199e-05 0.118
GKAP1|80318 0.3313 5.647e-05 0.118
FNTB|2342 0.3312 5.68e-05 0.118
MARK3|4140 0.3307 5.832e-05 0.118
FZD5|7855 -0.3267 7.25e-05 0.125
Clinical variable #10: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  KIDNEY CHROMOPHOBE 66
  KIDNEY CLEAR CELL RENAL CARCINOMA 533
  KIDNEY PAPILLARY RENAL CELL CARCINOMA 289
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

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

kruskal_wallis_P Q
NDUFA4L2|56901 4.696e-129 8.55e-125
ELTD1|64123 3.403e-128 3.1e-124
GPR4|2828 5.186e-128 3.15e-124
FLT1|2321 7e-128 3.19e-124
CDH13|1012 2.716e-127 9.89e-124
MYCT1|80177 8.397e-127 2.55e-123
VEGFA|7422 1.256e-126 3.08e-123
C3ORF70|285382 1.352e-126 3.08e-123
APLN|8862 2.013e-126 4.08e-123
ANGPT2|285 7.041e-126 1.28e-122
Clinical variable #11: 'NUMBER_PACK_YEARS_SMOKED'

No gene related to 'NUMBER_PACK_YEARS_SMOKED'.

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

NUMBER_PACK_YEARS_SMOKED Mean (SD) 30.63 (25)
  Significant markers N = 0
Clinical variable #12: 'YEAR_OF_TOBACCO_SMOKING_ONSET'

21 genes related to 'YEAR_OF_TOBACCO_SMOKING_ONSET'.

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

YEAR_OF_TOBACCO_SMOKING_ONSET Mean (SD) 1973.56 (16)
  Significant markers N = 21
  pos. correlated 6
  neg. correlated 15
List of top 10 genes differentially expressed by 'YEAR_OF_TOBACCO_SMOKING_ONSET'

Table S22.  Get Full Table List of top 10 genes significantly correlated to 'YEAR_OF_TOBACCO_SMOKING_ONSET' by Spearman correlation test

SpearmanCorr corrP Q
AGK|55750 -0.4665 2.461e-05 0.275
POM121|9883 -0.4599 3.303e-05 0.275
CD1B|910 0.5901 6.129e-05 0.275
PPAPDC1B|84513 0.4408 7.544e-05 0.275
NOM1|64434 -0.4385 8.322e-05 0.275
SLC2A13|114134 -0.4325 0.0001066 0.275
PTCD1|26024 -0.4264 0.0001363 0.275
IFITM1|8519 0.4264 0.0001367 0.275
NAPEPLD|222236 -0.4253 0.0001428 0.275
TYW1|55253 -0.4226 0.0001587 0.275
Clinical variable #13: 'RACE'

30 genes related to 'RACE'.

Table S23.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 2
  ASIAN 15
  BLACK OR AFRICAN AMERICAN 121
  WHITE 726
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S24.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
NOTCH2NL|388677 1.545e-25 2.81e-21
TUBB8|347688 2.27e-18 2.07e-14
LOC90784|90784 1.644e-16 9.98e-13
ULK4|54986 3.842e-15 1.75e-11
CROCCL1|84809 3.407e-14 1.13e-10
LRRC37A2|474170 4.186e-14 1.13e-10
LOC653113|653113 4.343e-14 1.13e-10
PRSS45|377047 5.078e-13 1.16e-09
CRYBB2|1415 7.53e-13 1.52e-09
FAM22A|728118 1.267e-12 2.31e-09
Clinical variable #14: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S25.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 42
  NOT HISPANIC OR LATINO 628
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 888

  • Number of genes = 18216

  • Number of clinical features = 14

Selected clinical features

  • Further details on clinical features selected for this analysis, please find a documentation on selected CDEs (Clinical Data Elements). The first column of the file is a formula to convert values and the second column is a clinical parameter name.

  • 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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