Correlation between mRNAseq expression and clinical features
Uterine Corpus Endometrioid 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/C1CC100N
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 542 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 5 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

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

  • 30 genes correlated to 'RADIATION_THERAPY'.

    • CNIH|10175 ,  CABP1|9478 ,  DUSP3|1845 ,  LOC644172|644172 ,  SNRNP40|9410 ,  ...

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • KIAA1324|57535 ,  L1CAM|3897 ,  PPAP2C|8612 ,  FOXA2|3170 ,  HIF3A|64344 ,  ...

  • 30 genes correlated to 'RESIDUAL_TUMOR'.

    • VRK3|51231 ,  TMEM171|134285 ,  SLC7A10|56301 ,  ADAMTS4|9507 ,  DGCR6|8214 ,  ...

  • 30 genes correlated to 'RACE'.

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

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 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=0        
YEARS_TO_BIRTH Spearman correlation test N=30 older N=18 younger N=12
RADIATION_THERAPY Wilcoxon test N=30 yes N=30 no N=0
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
RESIDUAL_TUMOR Kruskal-Wallis test N=30        
RACE Kruskal-Wallis test N=30        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

No gene 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) 0-225.5 (median=27.4)
  censored N = 459
  death N = 82
     
  Significant markers N = 0
Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

Table S2.  Basic characteristics of clinical feature: 'YEARS_TO_BIRTH'

YEARS_TO_BIRTH Mean (SD) 63.94 (11)
  Significant markers N = 30
  pos. correlated 18
  neg. correlated 12
List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

Table S3.  Get Full Table List of top 10 genes significantly correlated to 'YEARS_TO_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
DIO2|1734 -0.3506 4.637e-17 8.6e-13
S100A1|6271 0.3359 1.034e-15 9.59e-12
FAM107A|11170 0.3322 2.243e-15 1.39e-11
PTCH1|5727 -0.3294 3.892e-15 1.8e-11
MGAT4A|11320 0.3216 1.871e-14 6.94e-11
DUSP9|1852 0.3202 1.985e-13 6.14e-10
FBXL16|146330 0.3083 2.336e-13 6.19e-10
EEF2|1938 -0.307 3.023e-13 7.01e-10
GPR158|57512 0.3327 4.613e-13 9.5e-10
PTGS1|5742 0.3039 5.295e-13 9.82e-10
Clinical variable #3: 'RADIATION_THERAPY'

30 genes related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 288
  YES 220
     
  Significant markers N = 30
  Higher in YES 30
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATION_THERAPY'

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

W(pos if higher in 'YES') wilcoxontestP Q AUC
CNIH|10175 38231 6.449e-05 0.215 0.6034
CABP1|9478 24333.5 6.916e-05 0.215 0.6038
DUSP3|1845 38169 7.56e-05 0.215 0.6024
LOC644172|644172 25262 9.055e-05 0.215 0.6013
SNRNP40|9410 38085 9.357e-05 0.215 0.6011
ALPL|249 25383 0.0001226 0.215 0.5994
PDLIM3|27295 37952 0.0001305 0.215 0.599
LOC100128573|100128573 15233.5 0.000133 0.215 0.6115
GHITM|27069 37932 0.0001371 0.215 0.5987
PEMT|10400 25475 0.0001539 0.215 0.5979
Clinical variable #4: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

Table S6.  Basic characteristics of clinical feature: 'HISTOLOGICAL_TYPE'

HISTOLOGICAL_TYPE Labels N
  ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA 406
  MIXED SEROUS AND ENDOMETRIOID 22
  SEROUS ENDOMETRIAL ADENOCARCINOMA 114
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S7.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

kruskal_wallis_P Q
KIAA1324|57535 1.448e-43 2.68e-39
L1CAM|3897 3.192e-42 2.96e-38
PPAP2C|8612 4.776e-41 2.95e-37
FOXA2|3170 5.013e-40 2.32e-36
HIF3A|64344 2.677e-39 9.56e-36
SLC6A12|6539 3.094e-39 9.56e-36
IL20RA|53832 7.469e-39 1.9e-35
SPDEF|25803 8.177e-39 1.9e-35
CDKN1A|1026 4.923e-38 1.01e-34
TFF3|7033 1.603e-37 2.97e-34
Clinical variable #5: 'RESIDUAL_TUMOR'

30 genes related to 'RESIDUAL_TUMOR'.

Table S8.  Basic characteristics of clinical feature: 'RESIDUAL_TUMOR'

RESIDUAL_TUMOR Labels N
  R0 373
  R1 22
  R2 17
  RX 37
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RESIDUAL_TUMOR'

Table S9.  Get Full Table List of top 10 genes differentially expressed by 'RESIDUAL_TUMOR'

kruskal_wallis_P Q
VRK3|51231 7.712e-06 0.14
TMEM171|134285 1.513e-05 0.14
SLC7A10|56301 3.393e-05 0.165
ADAMTS4|9507 5.652e-05 0.165
DGCR6|8214 5.767e-05 0.165
ZNF649|65251 5.99e-05 0.165
ARHGAP17|55114 6.891e-05 0.165
C6ORF97|80129 8.327e-05 0.165
KCNQ2|3785 8.562e-05 0.165
NYX|60506 8.917e-05 0.165
Clinical variable #6: 'RACE'

30 genes related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 4
  ASIAN 20
  BLACK OR AFRICAN AMERICAN 107
  NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 9
  WHITE 373
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S11.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
LRRC37A2|474170 6.659e-18 1.23e-13
LOC90784|90784 3.767e-16 3.49e-12
ACTB|60 1.865e-15 1.15e-11
SORD|6652 2.595e-15 1.2e-11
PPIL3|53938 5.205e-15 1.86e-11
EIF5AL1|143244 6.031e-15 1.86e-11
DHRS4L1|728635 1.245e-14 3.3e-11
ANXA2P3|305 3.845e-14 8.91e-11
LRRC37A|9884 4.447e-14 9.16e-11
LOC644165|644165 9.262e-14 1.72e-10
Clinical variable #7: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 15
  NOT HISPANIC OR LATINO 375
     
  Significant markers N = 0
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 = 542

  • Number of genes = 18545

  • Number of clinical features = 7

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)