Correlation between mRNAseq expression and clinical features
Esophageal Carcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1571B10
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/C1571B10
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 23680 genes and 10 clinical features across 174 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 6 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • MCM2|4171_CALCULATED ,  TMC5|79838_CALCULATED ,  H1FX|8971_CALCULATED ,  CENPA|1058_CALCULATED ,  HAT1|8520_CALCULATED ,  ...

  • 30 genes correlated to 'NEOPLASM_DISEASESTAGE'.

    • SEMA4G|57715_CALCULATED ,  PDX1|3651_CALCULATED ,  GPD1L|23171_CALCULATED ,  BC043213|?_CALCULATED ,  CHN2|1124_CALCULATED ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • BTNL3|10917_CALCULATED ,  TMEM45B|120224_CALCULATED ,  NOG|9241_CALCULATED ,  ACOT11|26027_CALCULATED ,  HMGCS2|3158_CALCULATED ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • GADD45G|10912_CALCULATED ,  CMTM8|152189_CALCULATED ,  GPR160|26996_CALCULATED ,  ZDHHC23|254887_CALCULATED ,  ABHD11|83451_CALCULATED ,  ...

  • 2 genes correlated to 'GENDER'.

    • TXLNG2P|246126_CALCULATED ,  AY927613|?_CALCULATED

  • 30 genes correlated to 'RACE'.

    • TMC5|79838_CALCULATED ,  CAGE1|285782_CALCULATED ,  TMTC3|160418_CALCULATED ,  CHODL|140578_CALCULATED ,  LRP12|29967_CALCULATED ,  ...

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'PATHOLOGY_M_STAGE', 'NUMBER_PACK_YEARS_SMOKED', 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=11 lower stage N=19
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=29 lower stage N=1
PATHOLOGY_M_STAGE Wilcoxon test   N=0        
GENDER Wilcoxon test N=2 male N=2 female N=0
NUMBER_PACK_YEARS_SMOKED Spearman correlation test   N=0        
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) 0.1-122.1 (median=12.6)
  censored N = 102
  death N = 71
     
  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) 62.62 (12)
  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
MCM2|4171_CALCULATED -0.4326 2.505e-09 5.93e-05
TMC5|79838_CALCULATED 0.4177 9.752e-09 6.11e-05
H1FX|8971_CALCULATED -0.4138 1.386e-08 6.11e-05
CENPA|1058_CALCULATED -0.4135 1.424e-08 6.11e-05
HAT1|8520_CALCULATED -0.4115 1.69e-08 6.11e-05
BC014150|?_CALCULATED -0.4442 1.949e-08 6.11e-05
CENPH|64946_CALCULATED -0.4097 1.975e-08 6.11e-05
RFC4|5984_CALCULATED -0.4092 2.064e-08 6.11e-05
RIPK3|11035_CALCULATED 0.4062 2.684e-08 6.22e-05
MCM5|4174_CALCULATED -0.4054 2.866e-08 6.22e-05
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 8
  STAGE IA 5
  STAGE IB 7
  STAGE II 1
  STAGE IIA 39
  STAGE IIB 29
  STAGE III 26
  STAGE IIIA 12
  STAGE IIIB 10
  STAGE IIIC 7
  STAGE IV 5
  STAGE IVA 4
     
  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) 2.41 (0.85)
  N
  T0 1
  T1 30
  T2 36
  T3 86
  T4 5
     
  Significant markers N = 30
  pos. correlated 11
  neg. correlated 19
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
BTNL3|10917_CALCULATED -0.4754 1.093e-08 0.000259
TMEM45B|120224_CALCULATED -0.4106 8.406e-08 0.000995
NOG|9241_CALCULATED 0.4116 1.841e-07 0.00145
ACOT11|26027_CALCULATED -0.3868 5.151e-07 0.00283
HMGCS2|3158_CALCULATED -0.4141 5.973e-07 0.00283
CLCN3|1182_CALCULATED -0.3773 1.024e-06 0.00358
CDS1|1040_CALCULATED -0.3768 1.059e-06 0.00358
ANO9|338440_CALCULATED -0.3712 1.574e-06 0.00416
FAM151A|338094_CALCULATED -0.3699 1.729e-06 0.00416
AK123947|?_CALCULATED 0.3696 1.756e-06 0.00416
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) 0.72 (0.82)
  N
  N0 71
  N1 65
  N2 12
  N3 8
     
  Significant markers N = 30
  pos. correlated 29
  neg. correlated 1
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
GADD45G|10912_CALCULATED 0.3603 3.832e-06 0.0795
CMTM8|152189_CALCULATED 0.3517 6.716e-06 0.0795
GPR160|26996_CALCULATED 0.3417 1.266e-05 0.1
ZDHHC23|254887_CALCULATED 0.3322 2.27e-05 0.128
ABHD11|83451_CALCULATED 0.3267 3.149e-05 0.128
LOC100507218|100507218_CALCULATED 0.3251 3.466e-05 0.128
PLA2G16|11145_CALCULATED 0.3236 3.771e-05 0.128
CLDN3|1365_CALCULATED 0.3192 4.877e-05 0.141
PRR15|222171_CALCULATED 0.3172 5.46e-05 0.141
ELF3|1999_CALCULATED 0.3155 6.036e-05 0.141
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 127
  class1 9
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

2 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 24
  MALE 150
     
  Significant markers N = 2
  Higher in MALE 2
  Higher in FEMALE 0
List of 2 genes differentially expressed by 'GENDER'

Table S12.  Get Full Table List of 2 genes differentially expressed by 'GENDER'. 15 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
TXLNG2P|246126_CALCULATED 1200 1.991e-06 0.00408 1
AY927613|?_CALCULATED 932 0.000153 0.226 0.7411
Clinical variable #8: 'NUMBER_PACK_YEARS_SMOKED'

No gene related to 'NUMBER_PACK_YEARS_SMOKED'.

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

NUMBER_PACK_YEARS_SMOKED Mean (SD) 35.15 (22)
  Significant markers N = 0
Clinical variable #9: 'RACE'

30 genes related to 'RACE'.

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

RACE Labels N
  ASIAN 41
  BLACK OR AFRICAN AMERICAN 2
  WHITE 111
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Clinical variable #10: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 3
  NOT HISPANIC OR LATINO 81
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 174

  • Number of genes = 23680

  • Number of clinical features = 10

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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