Correlation between mRNAseq expression and clinical features
Stomach and Esophageal carcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C13N22VB
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C13N22VB
Overview
Introduction

This pipeline uses various statistical tests to identify mRNAs whose log2 expression levels correlated to selected clinical features. The input file "STES-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt" is generated in the pipeline mRNAseq_Preprocess in the stddata run.

Summary

Testing the association between 18744 genes and 12 clinical features across 599 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'.

    • CCDC68|80323 ,  TMEM45B|120224 ,  RIPK3|11035 ,  MUC13|56667 ,  SLC17A5|26503 ,  ...

  • 30 genes correlated to 'PATHOLOGIC_STAGE'.

    • ST6GALNAC5|81849 ,  ISLR|3671 ,  GPBAR1|151306 ,  GREM1|26585 ,  TCF21|6943 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • KCNE4|23704 ,  ASPN|54829 ,  HAND2|9464 ,  DUOX1|53905 ,  ST6GALNAC5|81849 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • GPBAR1|151306 ,  IFFO2|126917 ,  CDHR5|53841 ,  SLC18A2|6571 ,  DUSP7|1849 ,  ...

  • 4 genes correlated to 'GENDER'.

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

  • 30 genes correlated to 'RADIATION_THERAPY'.

    • LMLN|89782 ,  TANC2|26115 ,  RPS25|6230 ,  DBNDD2|55861 ,  DHX8|1659 ,  ...

  • 30 genes correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

    • EIF3F|8665 ,  EEF1A1P9|441032 ,  RPL10A|4736 ,  EEA1|8411 ,  MT1F|4494 ,  ...

  • 30 genes correlated to 'NUMBER_PACK_YEARS_SMOKED'.

    • SF3B14|51639 ,  ZMYND19|116225 ,  CCPG1|9236 ,  NIT2|56954 ,  LOC100125556|100125556 ,  ...

  • 30 genes correlated to 'RACE'.

    • UTS2|10911 ,  POM121L10P|646074 ,  SIRPB2|284759 ,  LOC162632|162632 ,  LOC441294|441294 ,  ...

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'PATHOLOGY_M_STAGE', 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=22 younger N=8
PATHOLOGIC_STAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=28 lower stage N=2
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=15 lower stage N=15
PATHOLOGY_M_STAGE Wilcoxon test   N=0        
GENDER Wilcoxon test N=4 male N=4 female N=0
RADIATION_THERAPY Wilcoxon test N=30 yes N=30 no N=0
KARNOFSKY_PERFORMANCE_SCORE Spearman correlation test N=30 higher score N=25 lower score N=5
NUMBER_PACK_YEARS_SMOKED Spearman correlation test N=30 higher number_pack_years_smoked N=10 lower number_pack_years_smoked N=20
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) 0-122.3 (median=14)
  censored N = 358
  death N = 240
     
  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) 64.68 (11)
  Significant markers N = 30
  pos. correlated 22
  neg. correlated 8
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
CCDC68|80323 0.2851 1.703e-12 3.19e-08
TMEM45B|120224 0.2804 4.005e-12 3.75e-08
RIPK3|11035 0.2759 9.077e-12 5.67e-08
MUC13|56667 0.2741 1.531e-11 7.15e-08
SLC17A5|26503 0.2717 1.907e-11 7.15e-08
CTH|1491 0.2696 2.756e-11 8.01e-08
ENAH|55740 -0.2692 2.992e-11 8.01e-08
PRSS3|5646 0.2692 3.461e-11 8.11e-08
ZNF385A|25946 -0.266 5.129e-11 1.07e-07
C6ORF222|389384 0.2692 8.073e-11 1.51e-07
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 10
  STAGE IA 21
  STAGE IB 45
  STAGE II 30
  STAGE IIA 84
  STAGE IIB 87
  STAGE III 29
  STAGE IIIA 88
  STAGE IIIB 66
  STAGE IIIC 44
  STAGE IV 46
  STAGE IVA 4
     
  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
ST6GALNAC5|81849 2.179e-12 1.69e-08
ISLR|3671 2.606e-12 1.69e-08
GPBAR1|151306 2.697e-12 1.69e-08
GREM1|26585 9.432e-12 4.42e-08
TCF21|6943 1.428e-11 5.36e-08
TNFSF4|7292 2.592e-11 8.1e-08
RSPO3|84870 3.846e-11 9.31e-08
JMJD7-PLA2G4B|8681 3.975e-11 9.31e-08
GGT5|2687 5.267e-11 1.01e-07
PODN|127435 5.386e-11 1.01e-07
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) 2.79 (0.88)
  N
  T0 1
  T1 53
  T2 130
  T3 269
  T4 120
     
  Significant markers N = 30
  pos. correlated 28
  neg. correlated 2
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
KCNE4|23704 0.3147 1.234e-14 1.47e-10
ASPN|54829 0.3135 1.571e-14 1.47e-10
HAND2|9464 0.3167 2.37e-14 1.48e-10
DUOX1|53905 -0.3085 4.273e-14 2e-10
ST6GALNAC5|81849 0.3057 7.375e-14 2.76e-10
CDH11|1009 0.3022 1.441e-13 4.5e-10
NALCN|259232 0.3048 2.046e-13 5.48e-10
CALD1|800 0.2987 2.848e-13 6.67e-10
THBS4|7060 0.2989 4.414e-13 7.9e-10
EPHA3|2042 0.296 4.701e-13 7.9e-10
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) 1.13 (1.1)
  N
  N0 199
  N1 181
  N2 92
  N3 90
     
  Significant markers N = 30
  pos. correlated 15
  neg. correlated 15
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
GPBAR1|151306 0.2582 5.198e-10 9.74e-06
IFFO2|126917 -0.2417 6.482e-09 4.26e-05
CDHR5|53841 0.2416 6.822e-09 4.26e-05
SLC18A2|6571 0.2374 1.247e-08 5.85e-05
DUSP7|1849 -0.2324 2.486e-08 8.08e-05
TP53AIP1|63970 -0.2525 2.976e-08 8.08e-05
TFAP2A|7020 -0.2308 3.107e-08 8.08e-05
GOLM1|51280 0.2301 3.449e-08 8.08e-05
PLA2G4E|123745 -0.25 5.734e-08 0.000108
SIGLEC6|946 0.2296 5.81e-08 0.000108
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 502
  class1 36
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

4 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 173
  MALE 426
     
  Significant markers N = 4
  Higher in MALE 4
  Higher in FEMALE 0
List of 4 genes differentially expressed by 'GENDER'

Table S12.  Get Full Table List of 4 genes differentially expressed by 'GENDER'. 26 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
CYORF15A|246126 18312 3.244e-27 5.53e-24 0.9997
CYORF15B|84663 13609 5.123e-21 7.39e-18 0.9983
CA5BP|340591 19295 6.001e-20 7.5e-17 0.7382
HDHD1A|8226 22601 1.153e-13 9.6e-11 0.6933
Clinical variable #8: 'RADIATION_THERAPY'

30 genes related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 426
  YES 115
     
  Significant markers N = 30
  Higher in YES 30
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATION_THERAPY'

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

W(pos if higher in 'YES') wilcoxontestP Q AUC
LMLN|89782 32857 1.897e-08 0.000356 0.6707
TANC2|26115 31937 5.656e-07 0.0053 0.6519
RPS25|6230 17311 1.371e-06 0.00857 0.6466
DBNDD2|55861 17715 5.174e-06 0.0138 0.6384
DHX8|1659 31256 5.498e-06 0.0138 0.638
SRPK2|6733 31232 5.935e-06 0.0138 0.6375
KRT18|3875 17763 6.03e-06 0.0138 0.6374
VPS8|23355 31214 6.285e-06 0.0138 0.6372
DDX5|1655 31174 7.133e-06 0.0138 0.6363
MFN1|55669 31115 8.586e-06 0.0138 0.6351
Clinical variable #9: 'KARNOFSKY_PERFORMANCE_SCORE'

30 genes related to 'KARNOFSKY_PERFORMANCE_SCORE'.

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

KARNOFSKY_PERFORMANCE_SCORE Mean (SD) 73.58 (16)
  Significant markers N = 30
  pos. correlated 25
  neg. correlated 5
List of top 10 genes differentially expressed by 'KARNOFSKY_PERFORMANCE_SCORE'

Table S16.  Get Full Table List of top 10 genes significantly correlated to 'KARNOFSKY_PERFORMANCE_SCORE' by Spearman correlation test

SpearmanCorr corrP Q
EIF3F|8665 0.5958 1.044e-07 0.00145
EEF1A1P9|441032 0.5894 1.547e-07 0.00145
RPL10A|4736 0.5794 2.791e-07 0.00174
EEA1|8411 -0.5656 6.118e-07 0.00287
MT1F|4494 0.559 8.79e-07 0.00298
SF3B5|83443 0.5575 9.539e-07 0.00298
RPS27A|6233 0.5485 1.542e-06 0.00369
RPS10|6204 0.5482 1.575e-06 0.00369
BBS10|79738 -0.5457 1.787e-06 0.00372
RPL24|6152 0.5307 3.843e-06 0.0072
Clinical variable #10: 'NUMBER_PACK_YEARS_SMOKED'

30 genes related to 'NUMBER_PACK_YEARS_SMOKED'.

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

NUMBER_PACK_YEARS_SMOKED Mean (SD) 34.72 (22)
  Significant markers N = 30
  pos. correlated 10
  neg. correlated 20
List of top 10 genes differentially expressed by 'NUMBER_PACK_YEARS_SMOKED'

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

SpearmanCorr corrP Q
SF3B14|51639 -0.4157 2.296e-05 0.138
ZMYND19|116225 -0.4099 3.053e-05 0.138
CCPG1|9236 0.4071 3.506e-05 0.138
NIT2|56954 -0.4054 3.803e-05 0.138
LOC100125556|100125556 -0.4004 4.834e-05 0.138
PCGF1|84759 -0.3912 7.436e-05 0.138
C9ORF6|54942 -0.3883 8.475e-05 0.138
MRPS22|56945 -0.3827 0.0001093 0.138
TPRKB|51002 -0.3822 0.000112 0.138
NOL10|79954 -0.3815 0.0001156 0.138
Clinical variable #11: 'RACE'

30 genes related to 'RACE'.

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

RACE Labels N
  ASIAN 133
  BLACK OR AFRICAN AMERICAN 17
  NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 1
  WHITE 373
     
  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
UTS2|10911 2.448e-23 4.59e-19
POM121L10P|646074 2.786e-16 2.61e-12
SIRPB2|284759 4.16e-14 2.6e-10
LOC162632|162632 1.275e-13 5.97e-10
LOC441294|441294 7.756e-13 2.91e-09
C3ORF34|84984 4.84e-12 1.51e-08
SKA2|348235 5.983e-12 1.6e-08
CTAGE9|643854 9.271e-12 2.17e-08
PEX6|5190 1.637e-11 3.41e-08
MNAT1|4331 2.046e-11 3.84e-08
Clinical variable #12: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 10
  NOT HISPANIC OR LATINO 390
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 599

  • Number of genes = 18744

  • Number of clinical features = 12

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, logrank test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values comparing quantile intervals using the 'coxph' function in R. Kaplan-Meier survival curves were plotted using quantile intervals at c(0, 0.25, 0.50, 0.75, 1). If there is only one interval group, it will not try survival analysis.

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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