Correlation between mRNAseq expression and clinical features
Stomach Adenocarcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1H41QHW
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/C1H41QHW
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 23365 genes and 12 clinical features across 274 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'.

    • CXCL1|2919_CALCULATED ,  SNORD52|26797_CALCULATED ,  TMEM240|339453_CALCULATED ,  PEX7|5191_CALCULATED ,  TMEM132C|92293_CALCULATED ,  ...

  • 30 genes correlated to 'NEOPLASM_DISEASESTAGE'.

    • FMO2|2327_CALCULATED ,  GNB4|59345_CALCULATED ,  METAZOA_SRP|?|35OF109_CALCULATED ,  LOC641298|641298|1OF2_CALCULATED ,  ABI3BP|25890_CALCULATED ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • GNB4|59345_CALCULATED ,  NEXN|91624_CALCULATED ,  SNTB2|6645_CALCULATED ,  PLN|5350_CALCULATED ,  KCNE4|23704_CALCULATED ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • ABCA6|23460_CALCULATED ,  BX538254|?_CALCULATED ,  DYNC2H1|79659_CALCULATED ,  C1ORF150|148823_CALCULATED ,  SIGLEC6|946_CALCULATED ,  ...

  • 1 gene correlated to 'GENDER'.

    • AY927613|?_CALCULATED

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • MFAP5|8076_CALCULATED ,  FRMD6|122786_CALCULATED ,  DCN|1634_CALCULATED ,  ZFPM2|23414_CALCULATED ,  LY86|9450_CALCULATED ,  ...

  • 30 genes correlated to 'COMPLETENESS_OF_RESECTION'.

    • METAZOA_SRP|?|35OF109_CALCULATED ,  RPPH1|85495_CALCULATED ,  METAZOA_SRP|?|38OF109_CALCULATED ,  ZBTB3|79842_CALCULATED ,  GLTSCR1|29998_CALCULATED ,  ...

  • 30 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

    • SIGLEC6|946_CALCULATED ,  ABCA6|23460_CALCULATED ,  BX538254|?_CALCULATED ,  GHRL|51738_CALCULATED ,  GPR20|2843_CALCULATED ,  ...

  • 30 genes correlated to 'RACE'.

    • AK055746|?_CALCULATED ,  RGPD4|285190_CALCULATED ,  NPIPL2|440348_CALCULATED ,  LOC23117|?|2OF4_CALCULATED ,  WASH3P|374666_CALCULATED ,  ...

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'PATHOLOGY_M_STAGE', and 'RADIATIONS_RADIATION_REGIMENINDICATION'.

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=20 younger N=10
NEOPLASM_DISEASESTAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=30 lower stage N=0
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=28 lower stage N=2
PATHOLOGY_M_STAGE Wilcoxon test   N=0        
GENDER Wilcoxon test N=1 male N=1 female N=0
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
RADIATIONS_RADIATION_REGIMENINDICATION Wilcoxon test   N=0        
COMPLETENESS_OF_RESECTION Kruskal-Wallis test N=30        
NUMBER_OF_LYMPH_NODES Spearman correlation test N=30 higher number_of_lymph_nodes N=29 lower number_of_lymph_nodes N=1
RACE Kruskal-Wallis test N=30        
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) 0-105.1 (median=12.8)
  censored N = 199
  death N = 74
     
  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) 65.75 (11)
  Significant markers N = 30
  pos. correlated 20
  neg. correlated 10
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
CXCL1|2919_CALCULATED 0.3135 1.683e-07 0.00393
SNORD52|26797_CALCULATED 0.3011 6.176e-07 0.00589
TMEM240|339453_CALCULATED -0.2972 7.558e-07 0.00589
PEX7|5191_CALCULATED 0.2938 1.03e-06 0.00602
TMEM132C|92293_CALCULATED -0.3038 1.46e-06 0.00682
KIAA0845|?_CALCULATED -0.2844 2.314e-06 0.00805
CSF2|1437_CALCULATED 0.2909 2.411e-06 0.00805
SPTBN4|57731_CALCULATED -0.276 4.712e-06 0.0124
ACAT2|39_CALCULATED 0.2743 5.387e-06 0.0124
SNORD35A|26816_CALCULATED 0.2728 6.367e-06 0.0124
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 2
  STAGE IA 10
  STAGE IB 27
  STAGE II 23
  STAGE IIA 29
  STAGE IIB 44
  STAGE III 3
  STAGE IIIA 42
  STAGE IIIB 31
  STAGE IIIC 23
  STAGE IV 25
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'NEOPLASM_DISEASESTAGE'

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) 2.92 (0.86)
  N
  T1 13
  T2 70
  T3 107
  T4 75
     
  Significant markers N = 30
  pos. correlated 30
  neg. correlated 0
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
GNB4|59345_CALCULATED 0.4138 2.187e-12 5.11e-08
NEXN|91624_CALCULATED 0.3986 1.588e-11 1.85e-07
SNTB2|6645_CALCULATED 0.3862 7.404e-11 5.61e-07
PLN|5350_CALCULATED 0.3834 1.047e-10 5.61e-07
KCNE4|23704_CALCULATED 0.3822 1.2e-10 5.61e-07
PPP1R12A|4659_CALCULATED 0.3794 1.677e-10 6.53e-07
RYR2|6262_CALCULATED 0.3781 1.974e-10 6.59e-07
AF268386|?_CALCULATED 0.3743 3.093e-10 9.03e-07
NPTX1|4884_CALCULATED 0.3739 3.495e-10 9.07e-07
CALD1|800_CALCULATED 0.3723 3.894e-10 9.1e-07
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) 1.2 (1.1)
  N
  N0 91
  N1 76
  N2 46
  N3 49
     
  Significant markers N = 30
  pos. correlated 28
  neg. correlated 2
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
ABCA6|23460_CALCULATED 0.2893 1.913e-06 0.0336
BX538254|?_CALCULATED 0.2821 3.516e-06 0.0336
DYNC2H1|79659_CALCULATED 0.2743 6.608e-06 0.0336
C1ORF150|148823_CALCULATED 0.276 8.054e-06 0.0336
SIGLEC6|946_CALCULATED 0.2712 8.47e-06 0.0336
ITPR1|3708_CALCULATED 0.271 8.636e-06 0.0336
DTX1|1840_CALCULATED 0.2638 1.517e-05 0.0362
HDC|3067_CALCULATED 0.2631 1.604e-05 0.0362
ABI3BP|25890_CALCULATED 0.2619 1.758e-05 0.0362
YPEL2|388403_CALCULATED 0.2617 1.775e-05 0.0362
Clinical variable #6: 'PATHOLOGY_M_STAGE'

No gene related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 243
  class1 18
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

One gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 103
  MALE 171
     
  Significant markers N = 1
  Higher in MALE 1
  Higher in FEMALE 0
List of one gene differentially expressed by 'GENDER'

Table S12.  Get Full Table List of one gene differentially expressed by 'GENDER'. 29 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
AY927613|?_CALCULATED 5635 6e-07 0.000501 0.6801
Clinical variable #8: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  STOMACH ADENOCARCINOMA DIFFUSE TYPE 51
  STOMACH ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 131
  STOMACH INTESTINAL ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 34
  STOMACH INTESTINAL ADENOCARCINOMA TUBULAR TYPE 36
  STOMACH INTESTINAL ADENOCARCINOMA  MUCINOUS TYPE 14
  STOMACH INTESTINAL ADENOCARCINOMA  PAPILLARY TYPE 5
  STOMACH ADENOCARCINOMA SIGNET RING TYPE 1
     
  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
MFAP5|8076_CALCULATED 2.422e-10 5.66e-06
FRMD6|122786_CALCULATED 9.61e-10 9.74e-06
DCN|1634_CALCULATED 1.25e-09 9.74e-06
ZFPM2|23414_CALCULATED 2.085e-09 1.17e-05
LY86|9450_CALCULATED 2.9e-09 1.17e-05
GEM|2669_CALCULATED 2.999e-09 1.17e-05
FAM70A|55026_CALCULATED 4.298e-09 1.43e-05
ARHGAP20|57569_CALCULATED 5.929e-09 1.56e-05
VIM|7431_CALCULATED 6.137e-09 1.56e-05
COLEC12|81035_CALCULATED 6.664e-09 1.56e-05
Clinical variable #9: 'RADIATIONS_RADIATION_REGIMENINDICATION'

No gene related to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

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

RADIATIONS_RADIATION_REGIMENINDICATION Labels N
  NO 6
  YES 268
     
  Significant markers N = 0
Clinical variable #10: 'COMPLETENESS_OF_RESECTION'

30 genes related to 'COMPLETENESS_OF_RESECTION'.

Table S16.  Basic characteristics of clinical feature: 'COMPLETENESS_OF_RESECTION'

COMPLETENESS_OF_RESECTION Labels N
  R0 217
  R1 9
  R2 10
  RX 22
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'COMPLETENESS_OF_RESECTION'

Clinical variable #11: 'NUMBER_OF_LYMPH_NODES'

30 genes related to 'NUMBER_OF_LYMPH_NODES'.

Table S18.  Basic characteristics of clinical feature: 'NUMBER_OF_LYMPH_NODES'

NUMBER_OF_LYMPH_NODES Mean (SD) 4.84 (7.1)
  Significant markers N = 30
  pos. correlated 29
  neg. correlated 1
List of top 10 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

Table S19.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER_OF_LYMPH_NODES' by Spearman correlation test

SpearmanCorr corrP Q
SIGLEC6|946_CALCULATED 0.2858 7.495e-06 0.0619
ABCA6|23460_CALCULATED 0.2857 7.524e-06 0.0619
BX538254|?_CALCULATED 0.285 7.947e-06 0.0619
GHRL|51738_CALCULATED 0.2808 1.09e-05 0.0622
GPR20|2843_CALCULATED 0.2782 1.331e-05 0.0622
DTX1|1840_CALCULATED 0.2732 1.915e-05 0.0641
C1ORF150|148823_CALCULATED 0.2749 2.172e-05 0.0641
NFASC|23114_CALCULATED 0.2709 2.268e-05 0.0641
ITPR1|3708_CALCULATED 0.2678 2.826e-05 0.0641
GALNTL1|57452_CALCULATED 0.2673 2.939e-05 0.0641
Clinical variable #12: 'RACE'

30 genes related to 'RACE'.

Table S20.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  ASIAN 73
  BLACK OR AFRICAN AMERICAN 4
  WHITE 156
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Methods & Data
Input

  • Expresson data file = STAD-TP.mRNAseq_RPKM_log2.txt

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

  • Number of patients = 274

  • Number of genes = 23365

  • 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)
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