Correlation between mRNAseq expression and clinical features
Colon Adenocarcinoma (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
doi:10.7908/C1057F35
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/C1057F35
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 18012 genes and 13 clinical features across 454 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • MTERF|7978 ,  MGA|23269 ,  AMH|268 ,  ZNF75A|7627 ,  DNM3|26052 ,  ...

  • 30 genes correlated to 'PATHOLOGIC_STAGE'.

    • RGL2|5863 ,  GFI1|2672 ,  TEAD3|7005 ,  AGPAT5|55326 ,  GSR|2936 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • RIMKLB|57494 ,  SOX11|6664 ,  C10ORF114|399726 ,  FSTL3|10272 ,  TCHH|7062 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • AGPAT5|55326 ,  GSR|2936 ,  NAT1|9 ,  PBK|55872 ,  PDE12|201626 ,  ...

  • 30 genes correlated to 'PATHOLOGY_M_STAGE'.

    • LAP3|51056 ,  IRF1|3659 ,  TYMS|7298 ,  GFI1|2672 ,  HOXA4|3201 ,  ...

  • 5 genes correlated to 'GENDER'.

    • CYORF15A|246126 ,  CYORF15B|84663 ,  CA5BP|340591 ,  HDHD1A|8226 ,  NCRNA00183|554203

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • MUC2|4583 ,  PLAGL2|5326 ,  SLC19A3|80704 ,  CREB3L1|90993 ,  SLC5A6|8884 ,  ...

  • 30 genes correlated to 'RESIDUAL_TUMOR'.

    • LOC150776|150776 ,  NSUN5P1|155400 ,  SPDYE8P|389517 ,  LOC100132287|100132287 ,  LOC100133331|100133331 ,  ...

  • 30 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

    • NPR3|4883 ,  GSR|2936 ,  AGPAT5|55326 ,  TEAD3|7005 ,  NAT1|9 ,  ...

  • 30 genes correlated to 'RACE'.

    • CROCCL1|84809 ,  ULK4|54986 ,  C14ORF167|55449 ,  SPDYE1|285955 ,  LOC441455|441455 ,  ...

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'RADIATION_THERAPY', 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
PATHOLOGIC_STAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=29 lower stage N=1
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=11 lower stage N=19
PATHOLOGY_M_STAGE Wilcoxon test N=30 class1 N=30 class0 N=0
GENDER Wilcoxon test N=5 male N=5 female N=0
RADIATION_THERAPY Wilcoxon test   N=0        
HISTOLOGICAL_TYPE Wilcoxon test N=30 colon mucinous adenocarcinoma N=30 colon adenocarcinoma N=0
RESIDUAL_TUMOR Kruskal-Wallis test N=30        
NUMBER_OF_LYMPH_NODES Spearman correlation test N=30 higher number_of_lymph_nodes N=11 lower number_of_lymph_nodes N=19
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) 0-148 (median=22)
  censored N = 353
  death N = 100
     
  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) 67 (13)
  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
MTERF|7978 -0.2652 1.15e-08 0.000207
MGA|23269 -0.2459 1.198e-07 0.00108
AMH|268 0.2386 4.805e-07 0.00288
ZNF75A|7627 -0.232 6.462e-07 0.00291
DNM3|26052 -0.2294 8.208e-07 0.00296
PPP1R10|5514 -0.2271 1.065e-06 0.0032
FGF8|2253 0.2774 4.951e-06 0.0101
VDAC2|7417 0.2112 5.929e-06 0.0101
CNTD2|79935 0.2102 6.901e-06 0.0101
EXT1|2131 -0.2095 7.076e-06 0.0101
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 74
  STAGE IA 1
  STAGE II 29
  STAGE IIA 138
  STAGE IIB 9
  STAGE IIC 1
  STAGE III 21
  STAGE IIIA 9
  STAGE IIIB 59
  STAGE IIIC 40
  STAGE IV 45
  STAGE IVA 17
  STAGE IVB 2
     
  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
RGL2|5863 1.43e-09 2.58e-05
GFI1|2672 1.68e-07 0.00116
TEAD3|7005 1.931e-07 0.00116
AGPAT5|55326 2.851e-07 0.00128
GSR|2936 5.026e-07 0.00181
NAT1|9 7.242e-07 0.00217
C5ORF23|79614 1.101e-06 0.00265
PBK|55872 1.179e-06 0.00265
CDCA2|157313 1.325e-06 0.00265
C13ORF15|28984 1.786e-06 0.00322
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) 2.9 (0.62)
  N
  T1 11
  T2 77
  T3 310
  T4 55
     
  Significant markers N = 30
  pos. correlated 29
  neg. correlated 1
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
RIMKLB|57494 0.2352 4.143e-07 0.00635
SOX11|6664 0.2311 1.01e-06 0.00635
C10ORF114|399726 0.2269 1.403e-06 0.00635
FSTL3|10272 0.2227 1.7e-06 0.00635
TCHH|7062 0.2286 1.818e-06 0.00635
CSRP2|1466 0.2205 2.144e-06 0.00635
C11ORF41|25758 0.2202 2.467e-06 0.00635
C5ORF23|79614 0.2219 2.821e-06 0.00635
HTR2B|3357 0.2202 3.936e-06 0.00788
CAMK2B|816 0.2267 5.487e-06 0.00988
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) 0.59 (0.78)
  N
  N0 267
  N1 105
  N2 82
     
  Significant markers N = 30
  pos. correlated 11
  neg. correlated 19
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
AGPAT5|55326 -0.3148 6.639e-12 1.2e-07
GSR|2936 -0.3067 2.412e-11 2.17e-07
NAT1|9 -0.3025 4.632e-11 2.78e-07
PBK|55872 -0.2938 1.794e-10 8.08e-07
PDE12|201626 -0.2884 3.829e-10 1.2e-06
NPR3|4883 0.3102 4.003e-10 1.2e-06
TEAD3|7005 0.2869 4.752e-10 1.22e-06
INTS10|55174 -0.2844 6.751e-10 1.52e-06
ESCO2|157570 -0.2832 8.741e-10 1.75e-06
CDCA2|157313 -0.2805 1.236e-09 2.23e-06
Clinical variable #6: 'PATHOLOGY_M_STAGE'

30 genes related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 331
  class1 64
     
  Significant markers N = 30
  Higher in class1 30
  Higher in class0 0
List of top 10 genes differentially expressed by 'PATHOLOGY_M_STAGE'

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

W(pos if higher in 'class1') wilcoxontestP Q AUC
LAP3|51056 5339 3.34e-10 6.02e-06 0.748
IRF1|3659 6079 6.775e-08 0.00061 0.713
TYMS|7298 6254 2.129e-07 0.00105 0.7048
GFI1|2672 6268 2.328e-07 0.00105 0.7041
HOXA4|3201 14725 4.486e-07 0.00134 0.6993
CXCL9|4283 6388 4.97e-07 0.00134 0.6985
C13ORF15|28984 14789 5.191e-07 0.00134 0.6981
CXCR6|10663 6414 6.63e-07 0.00149 0.6963
ZSCAN5A|79149 6482 8.876e-07 0.00167 0.694
RASGRP1|10125 6448 9.277e-07 0.00167 0.6938
Clinical variable #7: 'GENDER'

5 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 214
  MALE 240
     
  Significant markers N = 5
  Higher in MALE 5
  Higher in FEMALE 0
List of 5 genes differentially expressed by 'GENDER'

Table S13.  Get Full Table List of 5 genes differentially expressed by 'GENDER'. 25 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
CYORF15A|246126 13550 1.155e-30 2.31e-27 0.9905
CYORF15B|84663 10711 9.688e-25 1.16e-21 0.9784
CA5BP|340591 12044 1.498e-22 1.69e-19 0.7655
HDHD1A|8226 12294 8.643e-22 9.16e-19 0.7606
NCRNA00183|554203 14340 4.444e-16 3.64e-13 0.7208
Clinical variable #8: 'RADIATION_THERAPY'

No gene related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 361
  YES 9
     
  Significant markers N = 0
Clinical variable #9: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  COLON ADENOCARCINOMA 388
  COLON MUCINOUS ADENOCARCINOMA 61
     
  Significant markers N = 30
  Higher in COLON MUCINOUS ADENOCARCINOMA 30
  Higher in COLON ADENOCARCINOMA 0
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

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

W(pos if higher in 'COLON MUCINOUS ADENOCARCINOMA') wilcoxontestP Q AUC
MUC2|4583 19486 4.595e-16 8.28e-12 0.8233
PLAGL2|5326 4286 1.134e-15 1.02e-11 0.8189
SLC19A3|80704 4381.5 2.574e-15 1.55e-11 0.8149
CREB3L1|90993 19101 1.228e-14 5.53e-11 0.807
SLC5A6|8884 4609 1.74e-14 6.11e-11 0.8053
UQCC|55245 4628 2.036e-14 6.11e-11 0.8045
TAF4|6874 4676 3.021e-14 7.77e-11 0.8024
TOMM34|10953 4721 4.365e-14 9.83e-11 0.8005
AQP3|360 18858 8.976e-14 1.8e-10 0.7968
POFUT1|23509 4826 1.021e-13 1.84e-10 0.7961
Clinical variable #10: 'RESIDUAL_TUMOR'

30 genes related to 'RESIDUAL_TUMOR'.

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

RESIDUAL_TUMOR Labels N
  R0 326
  R1 3
  R2 24
  RX 25
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RESIDUAL_TUMOR'

Table S18.  Get Full Table List of top 10 genes differentially expressed by 'RESIDUAL_TUMOR'

kruskal_wallis_P Q
LOC150776|150776 1.707e-10 1.18e-06
NSUN5P1|155400 2.46e-10 1.18e-06
SPDYE8P|389517 2.481e-10 1.18e-06
LOC100132287|100132287 3.082e-10 1.18e-06
LOC100133331|100133331 3.264e-10 1.18e-06
RRN3P2|653390 6.011e-10 1.8e-06
POLR2J4|84820 1.328e-09 3.01e-06
LOC339047|339047 1.338e-09 3.01e-06
RPL36A|6173 2.056e-09 4.06e-06
RRP7B|91695 2.352e-09 4.06e-06
Clinical variable #11: 'NUMBER_OF_LYMPH_NODES'

30 genes related to 'NUMBER_OF_LYMPH_NODES'.

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

NUMBER_OF_LYMPH_NODES Mean (SD) 2.06 (4.4)
  Significant markers N = 30
  pos. correlated 11
  neg. correlated 19
List of top 10 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

Table S20.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER_OF_LYMPH_NODES' by Spearman correlation test

SpearmanCorr corrP Q
NPR3|4883 0.3272 1.398e-10 2.01e-06
GSR|2936 -0.299 2.745e-10 2.01e-06
AGPAT5|55326 -0.2976 3.351e-10 2.01e-06
TEAD3|7005 0.2831 2.476e-09 8e-06
NAT1|9 -0.2827 2.612e-09 8e-06
RGL2|5863 0.2826 2.666e-09 8e-06
C5ORF23|79614 0.2836 4.611e-09 1.19e-05
PBK|55872 -0.2744 8.195e-09 1.85e-05
MINPP1|9562 -0.2714 1.165e-08 2.3e-05
INTS10|55174 -0.2706 1.275e-08 2.3e-05
Clinical variable #12: 'RACE'

30 genes related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 11
  BLACK OR AFRICAN AMERICAN 58
  WHITE 213
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S22.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
CROCCL1|84809 8.124e-13 1.46e-08
ULK4|54986 1.982e-12 1.79e-08
C14ORF167|55449 4.703e-12 2.82e-08
SPDYE1|285955 5.088e-10 2.29e-06
LOC441455|441455 7.078e-10 2.55e-06
SPDYE6|729597 1.28e-09 3.84e-06
LOC100190986|100190986 4.545e-09 1.17e-05
NOTCH2NL|388677 8.41e-09 1.86e-05
SPDYE5|442590 9.274e-09 1.86e-05
BCO2|83875 1.681e-08 2.94e-05
Clinical variable #13: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S23.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 4
  NOT HISPANIC OR LATINO 267
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 454

  • Number of genes = 18012

  • Number of clinical features = 13

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