Correlation between mRNAseq expression and clinical features
Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C16Q1WDP
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/C16Q1WDP
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 18545 genes and 7 clinical features across 534 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 7 clinical features related to at least one genes.

  • 30 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • SRD5A1|6715 ,  CD3EAP|10849 ,  CPS1|1373 ,  MGAT4A|11320 ,  GDPD2|54857 ,  ...

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • DIO2|1734 ,  FAM107A|11170 ,  S100A1|6271 ,  PTCH1|5727 ,  MGAT4A|11320 ,  ...

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • KIAA1324|57535 ,  L1CAM|3897 ,  PPAP2C|8612 ,  FOXA2|3170 ,  SLC6A12|6539 ,  ...

  • 30 genes correlated to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

    • RPL23AP82|284942 ,  RPL23AP7|118433 ,  LOC341056|341056 ,  UBE2MP1|606551 ,  UBE2NL|389898 ,  ...

  • 30 genes correlated to 'COMPLETENESS_OF_RESECTION'.

    • TMEM171|134285 ,  SLC7A10|56301 ,  VRK3|51231 ,  DOK1|1796 ,  ARHGAP17|55114 ,  ...

  • 30 genes correlated to 'RACE'.

    • LRRC37A2|474170 ,  LOC90784|90784 ,  SORD|6652 ,  ACTB|60 ,  PPIL3|53938 ,  ...

  • 1 gene correlated to 'ETHNICITY'.

    • SEPT6|23157

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=18 longer survival N=12
YEARS_TO_BIRTH Spearman correlation test N=30 older N=19 younger N=11
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
RADIATIONS_RADIATION_REGIMENINDICATION Wilcoxon test N=30 yes N=30 no N=0
COMPLETENESS_OF_RESECTION Kruskal-Wallis test N=30        
RACE Kruskal-Wallis test N=30        
ETHNICITY Wilcoxon test N=1 not hispanic or latino N=1 hispanic or latino 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) 0.1-191.8 (median=23.3)
  censored N = 464
  death N = 69
     
  Significant markers N = 30
  associated with shorter survival 18
  associated with longer survival 12
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
SRD5A1|6715 2.7 3.552e-09 6.6e-05 0.669
CD3EAP|10849 2.7 4.498e-08 0.00042 0.665
CPS1|1373 1.26 3.756e-07 0.0023 0.669
MGAT4A|11320 1.6 2.038e-06 0.0061 0.667
GDPD2|54857 1.32 2.309e-06 0.0061 0.656
ALG12|79087 0.46 2.362e-06 0.0061 0.343
SCGB2A1|4246 0.86 2.555e-06 0.0061 0.309
MRPL15|29088 2.2 2.819e-06 0.0061 0.64
MBOAT2|129642 1.55 2.963e-06 0.0061 0.686
KIAA1324|57535 0.87 4.138e-06 0.0077 0.338
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) 63.95 (11)
  Significant markers N = 30
  pos. correlated 19
  neg. correlated 11
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
DIO2|1734 -0.345 2.565e-16 4.76e-12
FAM107A|11170 0.333 3.065e-15 2.84e-11
S100A1|6271 0.3289 6.907e-15 4.27e-11
PTCH1|5727 -0.327 1.002e-14 4.65e-11
MGAT4A|11320 0.3199 4.029e-14 1.49e-10
DUSP9|1852 0.3222 2.133e-13 6.59e-10
PTGS1|5742 0.3065 4.944e-13 1.27e-09
EEF2|1938 -0.3059 5.483e-13 1.27e-09
GPR158|57512 0.3297 1.09e-12 2.25e-09
HRASLS|57110 0.3112 1.274e-12 2.36e-09
Clinical variable #3: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA 400
  MIXED SEROUS AND ENDOMETRIOID 21
  SEROUS ENDOMETRIAL ADENOCARCINOMA 113
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

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

kruskal_wallis_P Q
KIAA1324|57535 9.629e-43 1.79e-38
L1CAM|3897 1.989e-41 1.84e-37
PPAP2C|8612 2.486e-40 1.54e-36
FOXA2|3170 5.157e-39 2.39e-35
SLC6A12|6539 1.456e-38 5.35e-35
CDKN1A|1026 1.792e-38 5.35e-35
HIF3A|64344 2.02e-38 5.35e-35
IL20RA|53832 3.079e-38 7.14e-35
SPDEF|25803 8.579e-38 1.77e-34
FIGNL2|401720 1.211e-36 2.25e-33
Clinical variable #4: 'RADIATIONS_RADIATION_REGIMENINDICATION'

30 genes related to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

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

RADIATIONS_RADIATION_REGIMENINDICATION Labels N
  NO 141
  YES 393
     
  Significant markers N = 30
  Higher in YES 30
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATIONS_RADIATION_REGIMENINDICATION'

Table S8.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS_RADIATION_REGIMENINDICATION'

W(pos if higher in 'YES') wilcoxontestP Q AUC
RPL23AP82|284942 15120 1.171e-15 2.17e-11 0.7271
RPL23AP7|118433 15401 4.929e-15 4.57e-11 0.7221
LOC341056|341056 16525.5 1.4e-12 6.96e-09 0.701
UBE2MP1|606551 16586.5 1.5e-12 6.96e-09 0.7007
UBE2NL|389898 16252 2.233e-12 8.28e-09 0.7
POTEE|445582 16291 3.221e-12 9.96e-09 0.6983
EDARADD|128178 16832 4.572e-12 1.21e-08 0.6962
PGAM4|441531 16884 5.771e-12 1.34e-08 0.6953
LOC100130932|100130932 17074 1.34e-11 2.76e-08 0.6919
PA2G4P4|647033 17127 1.69e-11 3.13e-08 0.6909
Clinical variable #5: 'COMPLETENESS_OF_RESECTION'

30 genes related to 'COMPLETENESS_OF_RESECTION'.

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

COMPLETENESS_OF_RESECTION Labels N
  R0 366
  R1 23
  R2 17
  RX 35
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'COMPLETENESS_OF_RESECTION'

Table S10.  Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS_OF_RESECTION'

kruskal_wallis_P Q
TMEM171|134285 1.579e-05 0.193
SLC7A10|56301 2.329e-05 0.193
VRK3|51231 6.761e-05 0.193
DOK1|1796 6.811e-05 0.193
ARHGAP17|55114 7.336e-05 0.193
NYX|60506 0.0001088 0.193
ADAMTS4|9507 0.0001379 0.193
C6ORF97|80129 0.0001379 0.193
AVPI1|60370 0.0001442 0.193
PSAT1|29968 0.0001453 0.193
Clinical variable #6: 'RACE'

30 genes related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 4
  ASIAN 20
  BLACK OR AFRICAN AMERICAN 102
  NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 9
  WHITE 371
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

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

kruskal_wallis_P Q
LRRC37A2|474170 1.177e-16 2.18e-12
LOC90784|90784 2.667e-16 2.47e-12
SORD|6652 1.917e-15 1.19e-11
ACTB|60 1.604e-14 7.44e-11
PPIL3|53938 3.785e-14 1.4e-10
EIF5AL1|143244 8.224e-14 2.54e-10
LRRC37A|9884 1.621e-13 4.18e-10
DHRS4L1|728635 1.802e-13 4.18e-10
ANXA2P3|305 6.509e-13 1.34e-09
LOC644165|644165 1.558e-12 2.89e-09
Clinical variable #7: 'ETHNICITY'

One gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 14
  NOT HISPANIC OR LATINO 370
     
  Significant markers N = 1
  Higher in NOT HISPANIC OR LATINO 1
  Higher in HISPANIC OR LATINO 0
List of one gene differentially expressed by 'ETHNICITY'

Table S14.  Get Full Table List of one gene differentially expressed by 'ETHNICITY'

W(pos if higher in 'NOT HISPANIC OR LATINO') wilcoxontestP Q AUC
SEPT6|23157 c("708", "3.925e-06") c("708", "3.925e-06") 0.0728 0.8633
Methods & Data
Input

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

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

  • Number of patients = 534

  • Number of genes = 18545

  • Number of clinical features = 7

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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