Correlation between mRNAseq expression and clinical features
Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1SF2V6G
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/C1SF2V6G
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 270 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one genes.

  • 30 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • CCDC13|152206 ,  IGF2BP3|10643 ,  CCNF|899 ,  PIGC|5279 ,  SPATA18|132671 ,  ...

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • LDHD|197257 ,  HIBCH|26275 ,  SLC22A18AS|5003 ,  SLC22A18|5002 ,  KLHL29|114818 ,  ...

  • 30 genes correlated to 'NEOPLASM_DISEASESTAGE'.

    • KIF20A|10112 ,  EPR1|8475 ,  UCK2|7371 ,  CENPA|1058 ,  CEP55|55165 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • EPR1|8475 ,  BUB1|699 ,  UCK2|7371 ,  CDCA8|55143 ,  CDCA2|157313 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • ACAD8|27034 ,  TBX18|9096 ,  TCTA|6988 ,  C9ORF140|89958 ,  HJURP|55355 ,  ...

  • 30 genes correlated to 'PATHOLOGY_M_STAGE'.

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

  • 10 genes correlated to 'GENDER'.

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

  • 30 genes correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

    • TMSB4Y|9087 ,  MS4A1|931 ,  C2ORF69|205327 ,  LOC646471|646471 ,  EIF1AY|9086 ,  ...

  • 2 genes correlated to 'YEAR_OF_TOBACCO_SMOKING_ONSET'.

    • LEPROTL1|23484 ,  CDHR3|222256

  • 30 genes correlated to 'RACE'.

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

  • No genes correlated to '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=19 longer survival N=11
YEARS_TO_BIRTH Spearman correlation test N=30 older N=18 younger N=12
NEOPLASM_DISEASESTAGE 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=22 lower stage N=8
PATHOLOGY_M_STAGE Wilcoxon test N=30 class1 N=30 class0 N=0
GENDER Wilcoxon test N=10 male N=10 female N=0
KARNOFSKY_PERFORMANCE_SCORE Spearman correlation test N=30 higher score N=22 lower score N=8
NUMBER_PACK_YEARS_SMOKED Spearman correlation test   N=0        
YEAR_OF_TOBACCO_SMOKING_ONSET Spearman correlation test N=2 higher year_of_tobacco_smoking_onset N=1 lower year_of_tobacco_smoking_onset N=1
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=21.5)
  censored N = 235
  death N = 34
     
  Significant markers N = 30
  associated with shorter survival 19
  associated with longer survival 11
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 0.49 1.377e-14 2.5e-10 0.18
IGF2BP3|10643 1.66 2.084e-12 1.9e-08 0.818
CCNF|899 3.1 1.026e-11 6.2e-08 0.813
PIGC|5279 10.1 1.149e-10 3.8e-07 0.793
SPATA18|132671 0.7 1.204e-10 3.8e-07 0.241
OIP5|11339 2.1 1.262e-10 3.8e-07 0.779
NICN1|84276 0.2 2.537e-10 6.5e-07 0.234
SYCE2|256126 2.2 3.905e-10 8.8e-07 0.75
ACCS|84680 0.56 5.151e-10 1e-06 0.352
PXMP4|11264 0.53 5.703e-10 1e-06 0.241
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) 61.31 (12)
  Significant markers N = 30
  pos. correlated 18
  neg. correlated 12
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 0.3103 2.543e-07 0.00263
HIBCH|26275 0.3088 2.926e-07 0.00263
SLC22A18AS|5003 0.2847 2.461e-06 0.0141
SLC22A18|5002 0.2801 3.638e-06 0.0141
KLHL29|114818 -0.2792 3.926e-06 0.0141
ATPAF1|64756 0.2727 6.674e-06 0.0153
GPI|2821 0.2725 6.776e-06 0.0153
BAZ1A|11177 -0.2712 7.549e-06 0.0153
SMARCE1|6605 -0.2705 7.936e-06 0.0153
AKR7A2|8574 0.2692 8.867e-06 0.0153
Clinical variable #3: 'NEOPLASM_DISEASESTAGE'

30 genes related to 'NEOPLASM_DISEASESTAGE'.

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

NEOPLASM_DISEASESTAGE Labels N
  STAGE I 168
  STAGE II 21
  STAGE III 49
  STAGE IV 14
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'NEOPLASM_DISEASESTAGE'

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

kruskal_wallis_P Q
KIF20A|10112 2.553e-15 3.13e-11
EPR1|8475 4.124e-15 3.13e-11
UCK2|7371 5.323e-15 3.13e-11
CENPA|1058 7.813e-15 3.13e-11
CEP55|55165 9.069e-15 3.13e-11
CDCA2|157313 1.045e-14 3.13e-11
CENPF|1063 1.384e-14 3.45e-11
TPX2|22974 1.582e-14 3.45e-11
KIFC1|3833 1.825e-14 3.45e-11
NEK2|4751 1.919e-14 3.45e-11
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 177
  T2 29
  T3 54
  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 0.4887 9.019e-17 1.62e-12
BUB1|699 0.4787 2.071e-16 1.86e-12
UCK2|7371 0.4739 4.479e-16 2.69e-12
CDCA8|55143 0.4718 6.276e-16 2.82e-12
CDCA2|157313 0.4707 8.485e-16 3.05e-12
NEK2|4751 0.469 1.264e-15 3.07e-12
TPX2|22974 0.4669 1.359e-15 3.07e-12
CEP55|55165 0.4669 1.364e-15 3.07e-12
NUF2|83540 0.4645 1.994e-15 3.99e-12
EXO1|9156 0.4601 3.943e-15 6.53e-12
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) 0.42 (0.6)
  N
  N0 45
  N1 22
  N2 4
     
  Significant markers N = 30
  pos. correlated 22
  neg. correlated 8
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
ACAD8|27034 -0.6699 1.679e-10 3.02e-06
TBX18|9096 0.6518 2.318e-09 2.09e-05
TCTA|6988 -0.6281 4.541e-09 2.72e-05
C9ORF140|89958 0.6203 7.971e-09 3.59e-05
HJURP|55355 0.6047 2.338e-08 8.42e-05
NEK2|4751 0.5932 5.001e-08 0.000148
STRA6|64220 0.605 7.438e-08 0.000148
KIF14|9928 0.5838 9.087e-08 0.000148
PRRX2|51450 0.6042 9.857e-08 0.000148
TPX2|22974 0.5821 1.01e-07 0.000148
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 91
  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 781 7.877e-06 0.0561 0.9536
MKI67IP|84365 775 1.101e-05 0.0561 0.9463
PABPC4|8761 770 1.451e-05 0.0561 0.9402
LOC728643|728643 763 2.122e-05 0.0561 0.9316
RPL6|6128 761 2.362e-05 0.0561 0.9292
ZBTB2|57621 757 2.922e-05 0.0561 0.9243
BYSL|705 754 3.423e-05 0.0561 0.9206
NAP1L1|4673 754 3.423e-05 0.0561 0.9206
RPL10A|4736 754 3.423e-05 0.0561 0.9206
RPLP0|6175 751 4.005e-05 0.0561 0.917
Clinical variable #7: 'GENDER'

10 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 72
  MALE 198
     
  Significant markers N = 10
  Higher in MALE 10
  Higher in FEMALE 0
List of 10 genes differentially expressed by 'GENDER'

Table S14.  Get Full Table List of 10 genes differentially expressed by 'GENDER'. 20 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
NCRNA00183|554203 2482 2.672e-16 6.01e-13 0.8259
HDHD1A|8226 2609 1.673e-15 2.74e-12 0.817
SLC2A9|56606 11505 1.227e-14 1.58e-11 0.807
NLRP6|171389 11026 1.441e-13 1.44e-10 0.7964
AOX1|316 11085 3.103e-12 2.54e-09 0.7776
MSH6|2956 3179 3.43e-12 2.68e-09 0.777
CCDC146|57639 11069 3.791e-12 2.84e-09 0.7764
ANKRD2|26287 11003 8.583e-12 5.52e-09 0.7718
ZMYND12|84217 10992 9.823e-12 6.1e-09 0.771
C1ORF186|440712 10932 2.037e-11 1.22e-08 0.7668
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) 92.13 (16)
  Significant markers N = 30
  pos. correlated 22
  neg. correlated 8
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
TMSB4Y|9087 -0.646 3.829e-06 0.0591
MS4A1|931 -0.5578 6.562e-06 0.0591
C2ORF69|205327 -0.5222 1.584e-05 0.088
LOC646471|646471 0.5212 1.956e-05 0.088
EIF1AY|9086 -0.5664 4.075e-05 0.147
KLHL5|51088 -0.4943 5.148e-05 0.154
LOC283922|283922 0.4882 6.568e-05 0.158
TTC21A|199223 0.4796 9.215e-05 0.158
SLC35E2|728661 0.4777 9.911e-05 0.158
TBC1D12|23232 0.476 0.0001055 0.158
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) 31.88 (28)
  Significant markers N = 0
Clinical variable #10: 'YEAR_OF_TOBACCO_SMOKING_ONSET'

2 genes 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) 1972.15 (16)
  Significant markers N = 2
  pos. correlated 1
  neg. correlated 1
List of 2 genes differentially expressed by 'YEAR_OF_TOBACCO_SMOKING_ONSET'

Table S19.  Get Full Table List of 2 genes significantly correlated to 'YEAR_OF_TOBACCO_SMOKING_ONSET' by Spearman correlation test

SpearmanCorr corrP Q
LEPROTL1|23484 0.5507 2.34e-05 0.252
CDHR3|222256 -0.5463 2.8e-05 0.252
Clinical variable #11: 'RACE'

30 genes related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 2
  ASIAN 5
  BLACK OR AFRICAN AMERICAN 60
  WHITE 188
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S21.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
NOTCH2NL|388677 1.824e-11 3.28e-07
LRRC37A2|474170 2.466e-09 2.22e-05
GSTM3|2947 1.255e-07 0.000753
CRYBB2|1415 1.709e-07 0.000769
LOC90784|90784 2.64e-07 0.00095
BEGAIN|57596 4.535e-07 0.00136
CN5H6.4|150384 9.533e-07 0.00245
LOC441455|441455 2.959e-06 0.00666
LQK1|642946 4.463e-06 0.00893
C21ORF56|84221 8.896e-06 0.016
Clinical variable #12: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S22.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 12
  NOT HISPANIC OR LATINO 221
     
  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 = 270

  • Number of genes = 17999

  • 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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