Correlation between mRNA expression and clinical features
Breast Invasive Carcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1KP814G
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Correlation between mRNA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1KP814G
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 17814 genes and 12 clinical features across 526 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 9 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • ESR1 ,  CNTNAP3 ,  KRT17 ,  C20ORF42 ,  MAGED4B ,  ...

  • 30 genes correlated to 'NEOPLASM_DISEASESTAGE'.

    • RANBP2 ,  RWDD3 ,  RPL11 ,  OR4D1 ,  LOC51252 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • RBBP5 ,  PPP2R5D ,  TMEM81 ,  CCNF ,  TBRG4 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • RWDD3 ,  RPL5 ,  HIST1H2AG ,  PBX1 ,  LRP6 ,  ...

  • 1 gene correlated to 'PATHOLOGY_M_STAGE'.

    • OR4C13

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • CDH1 ,  GLTSCR2 ,  ADRM1 ,  PPIL1 ,  ALG3 ,  ...

  • 30 genes correlated to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

    • SETD7 ,  FBXL10 ,  LOC285398 ,  IL6 ,  HBG1 ,  ...

  • 30 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

    • CSDE1 ,  RWDD3 ,  BCAR1 ,  STS ,  DDX20 ,  ...

  • 30 genes correlated to 'RACE'.

    • PSPH ,  CRYBB2 ,  IL27 ,  PRSS36 ,  RAI16 ,  ...

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'GENDER', 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=6 younger N=24
NEOPLASM_DISEASESTAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=21 lower stage N=9
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=14 lower stage N=16
PATHOLOGY_M_STAGE Wilcoxon test N=1 class1 N=1 class0 N=0
GENDER Wilcoxon test   N=0        
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
RADIATIONS_RADIATION_REGIMENINDICATION Wilcoxon test N=30 yes N=30 no N=0
NUMBER_OF_LYMPH_NODES Spearman correlation test N=30 higher number_of_lymph_nodes N=16 lower number_of_lymph_nodes N=14
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) 0.2-234.3 (median=31)
  censored N = 450
  death N = 75
     
  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) 58.08 (13)
  Significant markers N = 30
  pos. correlated 6
  neg. correlated 24
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
ESR1 0.4214 8.331e-24 1.48e-19
CNTNAP3 -0.3013 2.261e-12 2.01e-08
KRT17 -0.2952 6.472e-12 3.13e-08
C20ORF42 -0.2947 7.018e-12 3.13e-08
MAGED4B -0.2913 1.245e-11 4.13e-08
FOXD2 0.2907 1.391e-11 4.13e-08
KLK6 -0.2892 1.784e-11 4.28e-08
SYT8 -0.2882 2.11e-11 4.28e-08
SOSTDC1 -0.2879 2.195e-11 4.28e-08
PPP1R14C -0.2873 2.438e-11 4.28e-08
Clinical variable #3: 'NEOPLASM_DISEASESTAGE'

30 genes related to 'NEOPLASM_DISEASESTAGE'.

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

NEOPLASM_DISEASESTAGE Labels N
  STAGE I 50
  STAGE IA 33
  STAGE IB 6
  STAGE IIA 184
  STAGE IIB 111
  STAGE IIIA 77
  STAGE IIIB 15
  STAGE IIIC 19
  STAGE IV 14
  STAGE TIS 1
  STAGE X 13
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'NEOPLASM_DISEASESTAGE'

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

kruskal_wallis_P Q
RANBP2 2.151e-06 0.0282
RWDD3 5.233e-06 0.0282
RPL11 5.711e-06 0.0282
OR4D1 6.332e-06 0.0282
LOC51252 8.588e-06 0.0306
CHST5 1.746e-05 0.0457
OR51L1 1.903e-05 0.0457
FRMD1 2.053e-05 0.0457
DDX20 2.707e-05 0.0536
SATB2 3.584e-05 0.0621
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) 1.93 (0.72)
  N
  T1 133
  T2 311
  T3 59
  T4 20
     
  Significant markers N = 30
  pos. correlated 21
  neg. correlated 9
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
RBBP5 0.2759 1.374e-10 2.45e-06
PPP2R5D 0.2371 4.053e-08 0.000361
TMEM81 0.2324 7.583e-08 0.00045
CCNF 0.2287 1.236e-07 0.000551
TBRG4 0.226 1.748e-07 0.000586
TMEM63B 0.2251 1.974e-07 0.000586
SEPT10 -0.2198 3.856e-07 0.000981
RWDD3 -0.2176 5.027e-07 0.00112
ZBED5 -0.2165 5.779e-07 0.00114
RRM2 0.2125 9.338e-07 0.00166
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) 0.74 (0.88)
  N
  N0 255
  N1 170
  N2 61
  N3 29
     
  Significant markers N = 30
  pos. correlated 14
  neg. correlated 16
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
RWDD3 -0.2537 5.268e-09 9.38e-05
RPL5 -0.2316 1.062e-07 0.000946
HIST1H2AG 0.2272 1.866e-07 0.00111
PBX1 0.2181 5.796e-07 0.00238
LRP6 -0.2169 6.674e-07 0.00238
SRD5A2L 0.2124 1.149e-06 0.00315
C11ORF80 0.2118 1.239e-06 0.00315
RBBP8 -0.2094 1.638e-06 0.00346
CALM1 0.2088 1.749e-06 0.00346
ZMYM4 -0.2079 1.949e-06 0.00347
Clinical variable #6: 'PATHOLOGY_M_STAGE'

One gene related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 495
  class1 15
     
  Significant markers N = 1
  Higher in class1 1
  Higher in class0 0
List of one gene differentially expressed by 'PATHOLOGY_M_STAGE'

Table S11.  Get Full Table List of one gene differentially expressed by 'PATHOLOGY_M_STAGE'

W(pos if higher in 'class1') wilcoxontestP Q AUC
OR4C13 1239.5 1.12e-05 0.2 0.8327
Clinical variable #7: 'GENDER'

No gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 520
  MALE 6
     
  Significant markers N = 0
Clinical variable #8: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  INFILTRATING DUCTAL CARCINOMA 448
  INFILTRATING LOBULAR CARCINOMA 41
  MEDULLARY CARCINOMA 1
  MIXED HISTOLOGY (PLEASE SPECIFY) 12
  MUCINOUS CARCINOMA 2
  OTHER SPECIFY 21
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S14.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

kruskal_wallis_P Q
CDH1 3.005e-17 5.35e-13
GLTSCR2 3.981e-10 2.65e-06
ADRM1 4.47e-10 2.65e-06
PPIL1 9.746e-10 4.34e-06
ALG3 3.424e-09 1.22e-05
MGC7036 8.706e-09 1.88e-05
C6ORF129 8.992e-09 1.88e-05
C10ORF56 1.014e-08 1.88e-05
CIRBP 1.046e-08 1.88e-05
HSPC171 1.129e-08 1.88e-05
Clinical variable #9: 'RADIATIONS_RADIATION_REGIMENINDICATION'

30 genes related to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

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

RADIATIONS_RADIATION_REGIMENINDICATION Labels N
  NO 168
  YES 358
     
  Significant markers N = 30
  Higher in YES 30
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATIONS_RADIATION_REGIMENINDICATION'

Table S16.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS_RADIATION_REGIMENINDICATION'

W(pos if higher in 'YES') wilcoxontestP Q AUC
SETD7 37238 1.039e-05 0.0932 0.6191
FBXL10 22908.5 1.046e-05 0.0932 0.6191
LOC285398 37086 1.593e-05 0.0946 0.6166
IL6 23235.5 2.597e-05 0.105 0.6137
HBG1 36841.5 3.114e-05 0.105 0.6126
OR52J3 36794 3.538e-05 0.105 0.6118
KLHL34 23492 5.157e-05 0.109 0.6094
OR7A17 36569.5 6.398e-05 0.109 0.608
CRLF3 23576 6.423e-05 0.109 0.608
MGC33407 36555.5 6.635e-05 0.109 0.6078
Clinical variable #10: 'NUMBER_OF_LYMPH_NODES'

30 genes related to 'NUMBER_OF_LYMPH_NODES'.

Table S17.  Basic characteristics of clinical feature: 'NUMBER_OF_LYMPH_NODES'

NUMBER_OF_LYMPH_NODES Mean (SD) 1.82 (3.5)
  Significant markers N = 30
  pos. correlated 16
  neg. correlated 14
List of top 10 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

Table S18.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER_OF_LYMPH_NODES' by Spearman correlation test

SpearmanCorr corrP Q
CSDE1 -0.2397 9.632e-07 0.0168
RWDD3 -0.2328 1.998e-06 0.0168
BCAR1 0.2294 2.832e-06 0.0168
STS 0.2229 5.475e-06 0.0244
DDX20 -0.2181 8.777e-06 0.0263
ACY1L2 -0.2165 1.027e-05 0.0263
ARRDC1 0.214 1.296e-05 0.0263
NFATC1 -0.2134 1.375e-05 0.0263
HIST1H2AG 0.2131 1.416e-05 0.0263
SH3GL1 0.2114 1.659e-05 0.0263
Clinical variable #11: 'RACE'

30 genes related to 'RACE'.

Table S19.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 34
  BLACK OR AFRICAN AMERICAN 40
  WHITE 361
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S20.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
PSPH 2.725e-16 4.85e-12
CRYBB2 1.187e-13 1.06e-09
IL27 8.988e-11 4.51e-07
PRSS36 1.012e-10 4.51e-07
RAI16 1.656e-10 5.9e-07
DPF2 1.832e-09 5.44e-06
UTS2 2.16e-09 5.5e-06
CRCT1 1.266e-08 2.58e-05
MAB21L2 1.302e-08 2.58e-05
TNMD 2.08e-08 3.7e-05
Clinical variable #12: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S21.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 7
  NOT HISPANIC OR LATINO 372
     
  Significant markers N = 0
Methods & Data
Input

  • Expresson data file = BRCA-TP.medianexp.txt

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

  • Number of patients = 526

  • Number of genes = 17814

  • 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)
Copyright © 2015 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle