Correlation between mRNAseq expression and clinical features
Kidney Chromophobe (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C1CZ36JX
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1CZ36JX
Overview
Introduction

This pipeline uses various statistical tests to identify mRNAs whose log2 expression levels correlated to selected clinical features. The input file "KICH-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt" is generated in the pipeline mRNAseq_Preprocess in the stddata run.

Summary

Testing the association between 17843 genes and 12 clinical features across 66 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 4 clinical features related to at least one genes.

  • 30 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • CKAP2L|150468 ,  ZDHHC1|29800 ,  FBRS|64319 ,  FUK|197258 ,  NCAPG2|54892 ,  ...

  • 30 genes correlated to 'PATHOLOGIC_STAGE'.

    • C17ORF60|284021 ,  QRFPR|84109 ,  PVR|5817 ,  FUCA1|2517 ,  NTRK2|4915 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • GLT25D2|23127 ,  PCDHGA2|56113 ,  KLK4|9622 ,  PCDHGA1|56114 ,  CYP4V2|285440 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • UBE2QL1|134111 ,  DBNDD1|79007 ,  GARS|2617 ,  INTS8|55656 ,  CDKN3|1033 ,  ...

  • No genes correlated to 'YEARS_TO_BIRTH', 'PATHOLOGY_M_STAGE', 'GENDER', 'KARNOFSKY_PERFORMANCE_SCORE', 'NUMBER_PACK_YEARS_SMOKED', 'YEAR_OF_TOBACCO_SMOKING_ONSET', 'RACE', 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   N=NA   N=NA
YEARS_TO_BIRTH Spearman correlation test   N=0        
PATHOLOGIC_STAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=18 lower stage N=12
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=26 lower stage N=4
PATHOLOGY_M_STAGE Wilcoxon test   N=0        
GENDER Wilcoxon test   N=0        
KARNOFSKY_PERFORMANCE_SCORE Wilcoxon test   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=0        
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) 1-153.7 (median=72.7)
  censored N = 55
  death N = 10
     
  Significant markers N = 30
  associated with shorter survival NA
  associated with longer survival NA
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. For the survival curves, it compared quantile intervals at c(0, 0.25, 0.50, 0.75, 1) and did not try survival analysis if there is only one interval.

logrank_P Q C_index
CKAP2L|150468 2.87e-07 0.0051 0.922
ZDHHC1|29800 2.48e-06 0.015 0.105
FBRS|64319 2.72e-06 0.015 0.247
FUK|197258 4.11e-06 0.015 0.059
NCAPG2|54892 4.29e-06 0.015 0.908
PSMC2|5701 5.05e-06 0.015 0.89
ZKSCAN5|23660 5.71e-06 0.015 0.895
THUMPD1|55623 7.1e-06 0.016 0.183
ARPC1A|10552 8.56e-06 0.016 0.872
FAHD1|81889 1.02e-05 0.016 0.169
Clinical variable #2: 'YEARS_TO_BIRTH'

No gene related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 51.52 (14)
  Significant markers N = 0
Clinical variable #3: 'PATHOLOGIC_STAGE'

30 genes related to 'PATHOLOGIC_STAGE'.

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

PATHOLOGIC_STAGE Labels N
  STAGE I 21
  STAGE II 25
  STAGE III 14
  STAGE IV 6
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'PATHOLOGIC_STAGE'

Table S5.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGIC_STAGE'

kruskal_wallis_P Q
C17ORF60|284021 3.827e-05 0.146
QRFPR|84109 6.709e-05 0.146
PVR|5817 6.983e-05 0.146
FUCA1|2517 7.913e-05 0.146
NTRK2|4915 7.985e-05 0.146
GRB10|2887 8.589e-05 0.146
BRD4|23476 9.602e-05 0.146
HMGB2|3148 0.000103 0.146
MCM7|4176 0.0001175 0.146
TPMT|7172 0.0001408 0.146
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) 2.02 (0.85)
  N
  T1 21
  T2 25
  T3 18
  T4 2
     
  Significant markers N = 30
  pos. correlated 18
  neg. correlated 12
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
GLT25D2|23127 0.5415 2.664e-06 0.0262
PCDHGA2|56113 0.5353 4.348e-06 0.0262
KLK4|9622 -0.5309 4.529e-06 0.0262
PCDHGA1|56114 0.529 5.882e-06 0.0262
CYP4V2|285440 -0.52 7.637e-06 0.0273
MGC57346|401884 0.4893 3.059e-05 0.0772
FUCA1|2517 -0.4889 3.112e-05 0.0772
TYRO3|7301 0.4845 3.75e-05 0.0772
DNASE1L3|1776 -0.4836 3.904e-05 0.0772
REEP2|51308 0.4811 4.324e-05 0.0772
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 Mean (SD) 0.16 (0.47)
  N
  N0 40
  N1 3
  N2 2
     
  Significant markers N = 30
  pos. correlated 26
  neg. correlated 4
List of top 10 genes differentially expressed by 'PATHOLOGY_N_STAGE'

Table S9.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_N_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
UBE2QL1|134111 -0.5378 0.0001392 0.123
DBNDD1|79007 -0.5286 0.0001896 0.123
GARS|2617 0.5286 0.0001896 0.123
INTS8|55656 0.5228 0.0002294 0.123
CDKN3|1033 0.5182 0.0002662 0.123
KIAA0101|9768 0.5182 0.0002662 0.123
CENPE|1062 0.5176 0.0002714 0.123
POLQ|10721 0.5176 0.0002714 0.123
CDK1|983 0.517 0.0002767 0.123
CEP55|55165 0.517 0.0002767 0.123
Clinical variable #6: 'PATHOLOGY_M_STAGE'

No gene related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 34
  class1 2
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

No gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 27
  MALE 39
     
  Significant markers N = 0
Clinical variable #8: 'KARNOFSKY_PERFORMANCE_SCORE'

No gene related to 'KARNOFSKY_PERFORMANCE_SCORE'.

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

KARNOFSKY_PERFORMANCE_SCORE Labels N
  class100 10
  class90 3
     
  Significant markers N = 0
Clinical variable #9: 'NUMBER_PACK_YEARS_SMOKED'

No gene related to 'NUMBER_PACK_YEARS_SMOKED'.

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

NUMBER_PACK_YEARS_SMOKED Mean (SD) 25.09 (22)
  Significant markers N = 0
Clinical variable #10: 'YEAR_OF_TOBACCO_SMOKING_ONSET'

No gene related to 'YEAR_OF_TOBACCO_SMOKING_ONSET'.

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

YEAR_OF_TOBACCO_SMOKING_ONSET Mean (SD) 1973.75 (15)
  Significant markers N = 0
Clinical variable #11: 'RACE'

No gene related to 'RACE'.

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

RACE Labels N
  ASIAN 2
  BLACK OR AFRICAN AMERICAN 4
  WHITE 58
     
  Significant markers N = 0
Clinical variable #12: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 4
  NOT HISPANIC OR LATINO 32
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 66

  • Number of genes = 17843

  • 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, logrank test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values comparing quantile intervals using the 'coxph' function in R. Kaplan-Meier survival curves were plotted using quantile intervals at c(0, 0.25, 0.50, 0.75, 1). If there is only one interval group, it will not try survival analysis.

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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