Correlation between mRNAseq expression and clinical features
Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C13J3BWF
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C13J3BWF
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 18552 genes and 7 clinical features across 507 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 4 clinical features related to at least one genes.

  • 634 genes correlated to 'AGE'.

    • DIO2|1734 ,  PTCH1|5727 ,  FAM107A|11170 ,  S100A1|6271 ,  DUSP9|1852 ,  ...

  • 4973 genes correlated to 'HISTOLOGICAL.TYPE'.

    • KIAA1324|57535 ,  L1CAM|3897 ,  PPAP2C|8612 ,  FOXA2|3170 ,  IL20RA|53832 ,  ...

  • 180 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • RPL23AP82|284942 ,  RPL23AP7|118433 ,  LOC341056|341056 ,  UBE2MP1|606551 ,  EDARADD|128178 ,  ...

  • 303 genes correlated to 'RACE'.

    • SORD|6652 ,  LRRC37A2|474170 ,  ACTB|60 ,  LOC90784|90784 ,  DHRS4L1|728635 ,  ...

  • No genes correlated to 'Time to Death', 'COMPLETENESS.OF.RESECTION', 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
Time to Death Cox regression test   N=0        
AGE Spearman correlation test N=634 older N=365 younger N=269
HISTOLOGICAL TYPE Kruskal-Wallis test N=4973        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test N=180 yes N=180 no N=0
COMPLETENESS OF RESECTION Kruskal-Wallis test   N=0        
RACE Kruskal-Wallis test N=303        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'Time to Death'

No gene related to 'Time to Death'.

Table S1.  Basic characteristics of clinical feature: 'Time to Death'

Time to Death Duration (Months) 0-191.8 (median=22.8)
  censored N = 445
  death N = 60
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

634 genes related to 'AGE'.

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

AGE Mean (SD) 63.82 (11)
  Significant markers N = 634
  pos. correlated 365
  neg. correlated 269
List of top 10 genes differentially expressed by 'AGE'

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

SpearmanCorr corrP Q
DIO2|1734 -0.3583 9.029e-17 1.68e-12
PTCH1|5727 -0.3357 8.552e-15 1.59e-10
FAM107A|11170 0.3345 1.073e-14 1.99e-10
S100A1|6271 0.3269 4.583e-14 8.5e-10
DUSP9|1852 0.3294 2.64e-13 4.9e-09
MGAT4A|11320 0.3137 5.123e-13 9.5e-09
NR2F6|2063 0.3102 9.51e-13 1.76e-08
DLC1|10395 -0.3099 9.972e-13 1.85e-08
FBXL16|146330 0.3084 1.312e-12 2.43e-08
HIF3A|64344 0.3106 1.34e-12 2.49e-08
Clinical variable #3: 'HISTOLOGICAL.TYPE'

4973 genes related to 'HISTOLOGICAL.TYPE'.

Table S4.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA 382
  MIXED SEROUS AND ENDOMETRIOID 20
  SEROUS ENDOMETRIAL ADENOCARCINOMA 105
     
  Significant markers N = 4973
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

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

ANOVA_P Q
KIAA1324|57535 1.891e-40 3.51e-36
L1CAM|3897 4.539e-39 8.42e-35
PPAP2C|8612 5.93e-38 1.1e-33
FOXA2|3170 1.085e-37 2.01e-33
IL20RA|53832 8.331e-37 1.55e-32
HIF3A|64344 1.396e-36 2.59e-32
SLC6A12|6539 1.948e-36 3.61e-32
SPDEF|25803 6.618e-36 1.23e-31
TFF3|7033 1.262e-35 2.34e-31
CDKN1A|1026 1.829e-35 3.39e-31
Clinical variable #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

180 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S6.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 137
  YES 370
     
  Significant markers N = 180
  Higher in YES 180
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S7.  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 14413 8.497e-14 1.58e-09 0.7157
RPL23AP7|118433 14625 2.523e-13 4.68e-09 0.7115
LOC341056|341056 15270 6.098e-12 1.13e-07 0.6988
UBE2MP1|606551 15787.5 6.842e-11 1.27e-06 0.6885
EDARADD|128178 15842 8.764e-11 1.63e-06 0.6875
POTEE|445582 15594 1.242e-10 2.3e-06 0.6864
UBE2NL|389898 15592.5 1.879e-10 3.49e-06 0.685
LOC100130932|100130932 16064 2.368e-10 4.39e-06 0.6831
PGAM4|441531 16145 3.385e-10 6.28e-06 0.6815
TPI1P3|728402 14894 3.434e-10 6.37e-06 0.6839
Clinical variable #5: 'COMPLETENESS.OF.RESECTION'

No gene related to 'COMPLETENESS.OF.RESECTION'.

Table S8.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 351
  R1 22
  R2 17
  RX 30
     
  Significant markers N = 0
Clinical variable #6: 'RACE'

303 genes related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 4
  ASIAN 19
  BLACK OR AFRICAN AMERICAN 90
  NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 9
  WHITE 359
     
  Significant markers N = 303
List of top 10 genes differentially expressed by 'RACE'

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

ANOVA_P Q
SORD|6652 7.398e-15 1.37e-10
LRRC37A2|474170 5.173e-14 9.6e-10
ACTB|60 1.136e-13 2.11e-09
LOC90784|90784 4.18e-13 7.75e-09
DHRS4L1|728635 2.163e-12 4.01e-08
PPIL3|53938 3.66e-12 6.79e-08
ANXA2P3|305 6.493e-12 1.2e-07
EIF5AL1|143244 2.341e-11 4.34e-07
LOC644165|644165 1.001e-10 1.86e-06
CTAGE4|100128553 1.114e-10 2.07e-06
Clinical variable #7: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 13
  NOT HISPANIC OR LATINO 350
     
  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 = 507

  • Number of genes = 18552

  • Number of clinical features = 7

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

ANOVA analysis

For multi-class clinical features (ordinal or nominal), one-way analysis of variance (Howell 2002) was applied to compare the log2-expression levels between different clinical classes using 'anova' function in R

Student's t-test analysis

For two-class clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the log2-expression levels between the two clinical classes using 't.test' function in R

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] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[4] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[5] 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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