Correlation between mRNAseq expression and clinical features
Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
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/C12V2FCC
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 17999 genes and 12 clinical features across 289 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 9 clinical features related to at least one genes.

  • 30 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • CCDC13|152206 ,  IGF2BP3|10643 ,  OIP5|11339 ,  CEP55|55165 ,  CCNB2|9133 ,  ...

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • LDHD|197257 ,  HIBCH|26275 ,  SLC22A18|5002 ,  MFSD3|113655 ,  KLHL29|114818 ,  ...

  • 30 genes correlated to 'PATHOLOGIC_STAGE'.

    • KIF20A|10112 ,  CEP55|55165 ,  TPX2|22974 ,  EPR1|8475 ,  CDCA2|157313 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • EPR1|8475 ,  BUB1|699 ,  CEP55|55165 ,  TPX2|22974 ,  NUF2|83540 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • NEK2|4751 ,  C9ORF140|89958 ,  TCTA|6988 ,  TPX2|22974 ,  ACAD8|27034 ,  ...

  • 30 genes correlated to 'PATHOLOGY_M_STAGE'.

    • LYAR|55646 ,  MKI67IP|84365 ,  PABPC4|8761 ,  LOC728643|728643 ,  RPL6|6128 ,  ...

  • 8 genes correlated to 'GENDER'.

    • HDHD1A|8226 ,  NCRNA00183|554203 ,  SLC2A9|56606 ,  NLRP6|171389 ,  AOX1|316 ,  ...

  • 30 genes correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

    • STK19|8859 ,  LOC284440|284440 ,  PNPLA7|375775 ,  C9ORF95|54981 ,  GTF2H4|2968 ,  ...

  • 30 genes correlated to 'RACE'.

    • NOTCH2NL|388677 ,  LRRC37A2|474170 ,  GSTM3|2947 ,  CRYBB2|1415 ,  LOC90784|90784 ,  ...

  • No genes correlated to '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=30 shorter survival N=27 longer survival N=3
YEARS_TO_BIRTH Spearman correlation test N=30 older N=17 younger N=13
PATHOLOGIC_STAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=30 lower stage N=0
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=26 lower stage N=4
PATHOLOGY_M_STAGE Wilcoxon test N=30 class1 N=30 class0 N=0
GENDER Wilcoxon test N=8 male N=8 female N=0
KARNOFSKY_PERFORMANCE_SCORE Spearman correlation test N=30 higher score N=24 lower score N=6
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'

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=24.9)
  censored N = 244
  death N = 44
     
  Significant markers N = 30
  associated with shorter survival 27
  associated with longer survival 3
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
CCDC13|152206 0.48 0 0 0.194
IGF2BP3|10643 1.71 0 0 0.82
OIP5|11339 2.2 8.549e-15 5.1e-11 0.792
CEP55|55165 2.1 7.383e-14 3.3e-10 0.798
CCNB2|9133 2 1.22e-13 3.7e-10 0.812
PIGC|5279 12 1.237e-13 3.7e-10 0.792
KIF14|9928 1.96 1.602e-13 4.1e-10 0.806
CENPA|1058 2.2 2.266e-13 4.7e-10 0.803
CCNF|899 3 2.441e-13 4.7e-10 0.801
KIF11|3832 2.3 2.598e-13 4.7e-10 0.794
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) 61.4 (12)
  Significant markers N = 30
  pos. correlated 17
  neg. correlated 13
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
LDHD|197257 0.3049 1.602e-07 0.00288
HIBCH|26275 0.2924 5.281e-07 0.00475
SLC22A18|5002 0.2799 1.655e-06 0.00748
MFSD3|113655 0.278 1.948e-06 0.00748
KLHL29|114818 -0.2746 2.631e-06 0.00748
SLC22A18AS|5003 0.2738 2.829e-06 0.00748
ATPAF1|64756 0.2734 2.907e-06 0.00748
TNFAIP1|7126 -0.2682 4.573e-06 0.00931
APEH|327 0.268 4.656e-06 0.00931
BCAT2|587 0.2616 7.906e-06 0.0102
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 172
  STAGE II 22
  STAGE III 52
  STAGE IV 15
     
  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 1.295e-16 2.33e-12
CEP55|55165 8.828e-16 3.98e-12
TPX2|22974 9.463e-16 3.98e-12
EPR1|8475 9.465e-16 3.98e-12
CDCA2|157313 1.438e-15 3.98e-12
NUF2|83540 1.564e-15 3.98e-12
KIFC1|3833 1.629e-15 3.98e-12
CENPA|1058 1.927e-15 3.98e-12
CENPF|1063 1.989e-15 3.98e-12
NEK2|4751 2.81e-15 4.77e-12
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) 1.55 (0.84)
  N
  T1 192
  T2 33
  T3 60
  T4 2
     
  Significant markers N = 30
  pos. correlated 30
  neg. correlated 0
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
EPR1|8475 0.4901 2.886e-18 3.59e-14
BUB1|699 0.4823 3.987e-18 3.59e-14
CEP55|55165 0.4698 3.659e-17 1.68e-13
TPX2|22974 0.4697 3.733e-17 1.68e-13
NUF2|83540 0.4667 6.223e-17 2.24e-13
CDCA2|157313 0.466 8.049e-17 2.29e-13
CDCA8|55143 0.464 9.885e-17 2.29e-13
EXO1|9156 0.4639 1.017e-16 2.29e-13
UCK2|7371 0.4604 1.831e-16 3.66e-13
NEK2|4751 0.46 2.492e-16 3.9e-13
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) 0.44 (0.62)
  N
  N0 49
  N1 24
  N2 5
     
  Significant markers N = 30
  pos. correlated 26
  neg. correlated 4
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
NEK2|4751 0.6023 5.44e-09 4.55e-05
C9ORF140|89958 0.6012 5.877e-09 4.55e-05
TCTA|6988 -0.5977 7.577e-09 4.55e-05
TPX2|22974 0.5882 1.491e-08 5.41e-05
ACAD8|27034 -0.5881 1.503e-08 5.41e-05
CENPF|1063 0.579 2.804e-08 8.41e-05
TBX18|9096 0.5898 4.01e-08 0.000103
HJURP|55355 0.5717 4.574e-08 0.000103
KIF14|9928 0.5697 5.227e-08 0.000105
CEP55|55165 0.5641 7.516e-08 0.000132
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 94
  class1 9
     
  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
LYAR|55646 808 7.109e-06 0.0556 0.9551
MKI67IP|84365 801 1.04e-05 0.0556 0.9468
PABPC4|8761 793 1.594e-05 0.0556 0.9374
LOC728643|728643 790 1.867e-05 0.0556 0.9338
RPL6|6128 788 2.073e-05 0.0556 0.9314
ZBTB2|57621 781 2.979e-05 0.0556 0.9232
BYSL|705 780 3.135e-05 0.0556 0.922
RPL10A|4736 778 3.472e-05 0.0556 0.9196
NAP1L1|4673 777 3.654e-05 0.0556 0.9184
RPLP0|6175 777 3.654e-05 0.0556 0.9184
Clinical variable #7: 'GENDER'

8 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 76
  MALE 213
     
  Significant markers N = 8
  Higher in MALE 8
  Higher in FEMALE 0
List of 8 genes differentially expressed by 'GENDER'

Table S14.  Get Full Table List of 8 genes differentially expressed by 'GENDER'. 22 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
HDHD1A|8226 2860 5.894e-17 9.78e-14 0.8233
NCRNA00183|554203 2861 5.974e-17 9.78e-14 0.8233
SLC2A9|56606 13036 2.778e-15 3.57e-12 0.8053
NLRP6|171389 12508 3.998e-14 4e-11 0.7942
AOX1|316 12707 1.65e-13 1.48e-10 0.785
MSH6|2956 3656 1.296e-12 8.59e-10 0.7742
C1ORF186|440712 12513 1.614e-12 1e-09 0.773
ZMYND12|84217 12445 3.511e-12 2.11e-09 0.7688
Clinical variable #8: 'KARNOFSKY_PERFORMANCE_SCORE'

30 genes related to 'KARNOFSKY_PERFORMANCE_SCORE'.

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

KARNOFSKY_PERFORMANCE_SCORE Mean (SD) 87.66 (22)
  Significant markers N = 30
  pos. correlated 24
  neg. correlated 6
List of top 10 genes differentially expressed by 'KARNOFSKY_PERFORMANCE_SCORE'

Table S16.  Get Full Table List of top 10 genes significantly correlated to 'KARNOFSKY_PERFORMANCE_SCORE' by Spearman correlation test

SpearmanCorr corrP Q
STK19|8859 0.4914 5.671e-06 0.0207
LOC284440|284440 0.49 6.087e-06 0.0207
PNPLA7|375775 0.4868 7.139e-06 0.0207
C9ORF95|54981 0.4862 7.379e-06 0.0207
GTF2H4|2968 0.485 7.8e-06 0.0207
TUBE1|51175 0.4773 1.141e-05 0.0207
C14ORF181|400223 0.4762 1.199e-05 0.0207
DUT|1854 0.4723 1.449e-05 0.0207
PRR11|55771 -0.4889 1.52e-05 0.0207
PTGR2|145482 0.47 1.611e-05 0.0207
Clinical variable #9: 'NUMBER_PACK_YEARS_SMOKED'

No gene related to 'NUMBER_PACK_YEARS_SMOKED'.

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

NUMBER_PACK_YEARS_SMOKED Mean (SD) 32.08 (27)
  Significant markers N = 0
Clinical variable #10: 'YEAR_OF_TOBACCO_SMOKING_ONSET'

No gene related to 'YEAR_OF_TOBACCO_SMOKING_ONSET'.

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

YEAR_OF_TOBACCO_SMOKING_ONSET Mean (SD) 1972.29 (16)
  Significant markers N = 0
Clinical variable #11: 'RACE'

30 genes related to 'RACE'.

Table S19.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 2
  ASIAN 5
  BLACK OR AFRICAN AMERICAN 61
  WHITE 206
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S20.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
NOTCH2NL|388677 1.391e-12 2.5e-08
LRRC37A2|474170 4.373e-10 3.94e-06
GSTM3|2947 6.214e-08 0.000373
CRYBB2|1415 1.759e-07 0.000791
LOC90784|90784 2.7e-07 0.000972
CN5H6.4|150384 7.015e-07 0.0021
BEGAIN|57596 8.423e-07 0.00217
LOC441455|441455 2.583e-06 0.00581
LQK1|642946 3.162e-06 0.00618
ULK4|54986 3.433e-06 0.00618
Clinical variable #12: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 12
  NOT HISPANIC OR LATINO 241
     
  Significant markers N = 0
Methods & Data
Input
  • Expresson data file = KIRP-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt

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

  • Number of patients = 289

  • Number of genes = 17999

  • Number of clinical features = 12

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)