Correlation between mRNAseq expression and clinical features
Stomach Adenocarcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C1J102NQ
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/C1J102NQ
Overview
Introduction

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

Summary

Testing the association between 18694 genes and 13 clinical features across 415 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 12 clinical features related to at least one genes.

  • 30 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • NRP1|8829 ,  PRTG|283659 ,  PACS1|55690 ,  RBMS1|5937 ,  C1QTNF2|114898 ,  ...

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • PEX7|5191 ,  FUZ|80199 ,  METTL7A|25840 ,  TMEM132C|92293 ,  NEFH|4744 ,  ...

  • 30 genes correlated to 'PATHOLOGIC_STAGE'.

    • DEDD|9191 ,  EIF2B2|8892 ,  ISLR|3671 ,  NCOR1|9611 ,  ST6GALNAC5|81849 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • PPP1R12A|4659 ,  RYR2|6262 ,  SNTB2|6645 ,  TECR|9524 ,  OSTM1|28962 ,  ...

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • HDC|3067 ,  PELI2|57161 ,  DYNC2H1|79659 ,  SIGLEC6|946 ,  CNGB3|54714 ,  ...

  • 1 gene correlated to 'PATHOLOGY_M_STAGE'.

    • PPIAL4C|653598

  • 5 genes correlated to 'GENDER'.

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

  • 30 genes correlated to 'RADIATION_THERAPY'.

    • GALNT7|51809 ,  LMLN|89782 ,  RPL4|6124 ,  CATSPERB|79820 ,  ATP2B1|490 ,  ...

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • LY86|9450 ,  MFAP5|8076 ,  GNB4|59345 ,  CLEC2B|9976 ,  GGTA1|2681 ,  ...

  • 30 genes correlated to 'RESIDUAL_TUMOR'.

    • SAMD1|90378 ,  EEF1A1P9|441032 ,  RPPH1|85495 ,  PDDC1|347862 ,  ZBTB3|79842 ,  ...

  • 30 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

    • HDC|3067 ,  OSBPL9|114883 ,  CNGB3|54714 ,  SIGLEC6|946 ,  COL4A4|1286 ,  ...

  • 30 genes correlated to 'RACE'.

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

  • No genes correlated to '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=30   N=NA   N=NA
YEARS_TO_BIRTH Spearman correlation test N=30 older N=9 younger N=21
PATHOLOGIC_STAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=25 lower stage N=5
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=18 lower stage N=12
PATHOLOGY_M_STAGE Wilcoxon test N=1 class1 N=1 class0 N=0
GENDER Wilcoxon test N=5 male N=5 female N=0
RADIATION_THERAPY Wilcoxon test N=30 yes N=30 no N=0
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
RESIDUAL_TUMOR Kruskal-Wallis test N=30        
NUMBER_OF_LYMPH_NODES Spearman correlation test N=30 higher number_of_lymph_nodes N=28 lower number_of_lymph_nodes N=2
RACE Kruskal-Wallis test N=30        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

30 genes 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=15.3)
  censored N = 251
  death N = 163
     
  Significant markers N = 30
  associated with shorter survival NA
  associated with longer survival NA
List of top 10 genes differentially expressed by 'DAYS_TO_DEATH_OR_LAST_FUP'

Table S2.  Get Full Table List of top 10 genes significantly associated with 'Time to Death' by Cox regression test. For the survival curves, it compared quantile intervals at c(0, 0.25, 0.50, 0.75, 1) and did not try survival analysis if there is only one interval.

logrank_P Q C_index
NRP1|8829 8.23e-06 0.15 0.616
PRTG|283659 7.14e-05 0.25 0.605
PACS1|55690 9.1e-05 0.25 0.573
RBMS1|5937 0.00013 0.25 0.592
C1QTNF2|114898 0.000138 0.25 0.594
NKAPL|222698 0.000149 0.25 0.558
PPP1R3B|79660 0.000167 0.25 0.578
LOC113230|113230 0.000173 0.25 0.386
C20ORF54|113278 0.000177 0.25 0.396
WHAMML1|339005 0.000181 0.25 0.559
Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

Table S3.  Basic characteristics of clinical feature: 'YEARS_TO_BIRTH'

YEARS_TO_BIRTH Mean (SD) 65.69 (11)
  Significant markers N = 30
  pos. correlated 9
  neg. correlated 21
List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

Table S4.  Get Full Table List of top 10 genes significantly correlated to 'YEARS_TO_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
PEX7|5191 0.2676 4.371e-08 0.000817
FUZ|80199 -0.2599 1.079e-07 0.00101
METTL7A|25840 -0.2446 6.089e-07 0.00379
TMEM132C|92293 -0.259 8.385e-07 0.0038
NEFH|4744 -0.2401 1.016e-06 0.0038
PURA|5813 -0.2307 2.639e-06 0.00607
DCX|1641 -0.2401 2.985e-06 0.00607
SCARA3|51435 -0.2281 3.429e-06 0.00607
RNF10|9921 -0.2279 3.495e-06 0.00607
IL17D|53342 -0.2275 3.655e-06 0.00607
Clinical variable #3: 'PATHOLOGIC_STAGE'

30 genes related to 'PATHOLOGIC_STAGE'.

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGIC_STAGE'

PATHOLOGIC_STAGE Labels N
  STAGE I 2
  STAGE IA 16
  STAGE IB 39
  STAGE II 29
  STAGE IIA 38
  STAGE IIB 56
  STAGE III 3
  STAGE IIIA 74
  STAGE IIIB 57
  STAGE IIIC 37
  STAGE IV 41
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'PATHOLOGIC_STAGE'

Table S6.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGIC_STAGE'

kruskal_wallis_P Q
DEDD|9191 8.188e-08 0.000943
EIF2B2|8892 1.009e-07 0.000943
ISLR|3671 3.395e-07 0.00212
NCOR1|9611 7.828e-07 0.00334
ST6GALNAC5|81849 8.937e-07 0.00334
PPIAL4C|653598 1.325e-06 0.00405
RBM23|55147 1.516e-06 0.00405
RAB3IL1|5866 2.343e-06 0.00476
MALAT1|378938 2.559e-06 0.00476
VCAM1|7412 3.013e-06 0.00476
Clinical variable #4: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'

PATHOLOGY_T_STAGE Mean (SD) 2.96 (0.85)
  N
  T1 22
  T2 88
  T3 181
  T4 115
     
  Significant markers N = 30
  pos. correlated 25
  neg. correlated 5
List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S8.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
PPP1R12A|4659 0.2942 1.497e-09 2.8e-05
RYR2|6262 0.2863 4.449e-09 3.42e-05
SNTB2|6645 0.2843 5.488e-09 3.42e-05
TECR|9524 -0.2727 2.356e-08 0.00011
OSTM1|28962 0.2655 5.623e-08 0.00021
CALD1|800 0.2588 1.226e-07 0.000382
KCNE4|23704 0.2564 1.614e-07 0.000431
ZEB1|6935 0.2499 3.393e-07 0.000689
GNB4|59345 0.2495 3.526e-07 0.000689
RAB23|51715 0.2477 4.291e-07 0.000689
Clinical variable #5: 'PATHOLOGY_N_STAGE'

30 genes related to 'PATHOLOGY_N_STAGE'.

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY_N_STAGE'

PATHOLOGY_N_STAGE Mean (SD) 1.3 (1.1)
  N
  N0 123
  N1 112
  N2 80
  N3 82
     
  Significant markers N = 30
  pos. correlated 18
  neg. correlated 12
List of top 10 genes differentially expressed by 'PATHOLOGY_N_STAGE'

Table S10.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_N_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
HDC|3067 0.2347 2.624e-06 0.0491
PELI2|57161 0.2204 9.336e-06 0.0873
DYNC2H1|79659 0.2116 2.122e-05 0.108
SIGLEC6|946 0.2138 2.342e-05 0.108
CNGB3|54714 0.2378 2.89e-05 0.108
L3MBTL3|84456 0.2059 3.565e-05 0.109
PDK4|5166 0.2044 4.078e-05 0.109
RAD23A|5886 -0.2029 4.648e-05 0.109
FBXO47|494188 -0.3156 5.996e-05 0.114
EIF4EBP1|1978 -0.1991 6.477e-05 0.114
Clinical variable #6: 'PATHOLOGY_M_STAGE'

One gene related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 367
  class1 27
     
  Significant markers N = 1
  Higher in class1 1
  Higher in class0 0
List of one gene differentially expressed by 'PATHOLOGY_M_STAGE'

Table S12.  Get Full Table List of one gene differentially expressed by 'PATHOLOGY_M_STAGE'

W(pos if higher in 'class1') wilcoxontestP Q AUC
PPIAL4C|653598 6328 4.529e-06 0.0847 0.7801
Clinical variable #7: 'GENDER'

5 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 147
  MALE 268
     
  Significant markers N = 5
  Higher in MALE 5
  Higher in FEMALE 0
List of 5 genes differentially expressed by 'GENDER'

Table S14.  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 10448 6.693e-24 1.25e-20 0.9996
CYORF15B|84663 6952 5.382e-17 7.19e-14 0.9977
CA5BP|340591 10144 2.962e-16 3.69e-13 0.7425
NCRNA00183|554203 11725 8.977e-12 7.3e-09 0.7024
HDHD1A|8226 12461 5.932e-10 4.11e-07 0.6837
Clinical variable #8: 'RADIATION_THERAPY'

30 genes related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 303
  YES 72
     
  Significant markers N = 30
  Higher in YES 30
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATION_THERAPY'

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

W(pos if higher in 'YES') wilcoxontestP Q AUC
GALNT7|51809 14654 5.892e-06 0.0411 0.6717
LMLN|89782 14625 6.952e-06 0.0411 0.6704
RPL4|6124 7191 6.952e-06 0.0411 0.6704
CATSPERB|79820 14077 8.787e-06 0.0411 0.6698
ATP2B1|490 14543 1.103e-05 0.0412 0.6666
TC2N|123036 14417 2.2e-05 0.049 0.6608
PANK3|79646 14404 2.359e-05 0.049 0.6602
PIGA|5277 14385 2.612e-05 0.049 0.6594
ARHGAP26|23092 14376 2.741e-05 0.049 0.659
DKFZP434K028|26070 10253 3.01e-05 0.049 0.6723
Clinical variable #9: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  STOMACH ADENOCARCINOMA, SIGNET RING TYPE 12
  STOMACH, ADENOCARCINOMA, DIFFUSE TYPE 69
  STOMACH, ADENOCARCINOMA, NOT OTHERWISE SPECIFIED (NOS) 155
  STOMACH, INTESTINAL ADENOCARCINOMA, MUCINOUS TYPE 20
  STOMACH, INTESTINAL ADENOCARCINOMA, NOT OTHERWISE SPECIFIED (NOS) 73
  STOMACH, INTESTINAL ADENOCARCINOMA, PAPILLARY TYPE 7
  STOMACH, INTESTINAL ADENOCARCINOMA, TUBULAR TYPE 76
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

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

kruskal_wallis_P Q
LY86|9450 4.181e-16 7.82e-12
MFAP5|8076 1.08e-15 1.01e-11
GNB4|59345 4.345e-15 2.71e-11
CLEC2B|9976 1.868e-14 6e-11
GGTA1|2681 1.948e-14 6e-11
DCN|1634 2.37e-14 6e-11
TXNDC15|79770 2.385e-14 6e-11
MS4A7|58475 2.566e-14 6e-11
RNLS|55328 3.241e-14 6.73e-11
TM6SF1|53346 5.439e-14 9.68e-11
Clinical variable #10: 'RESIDUAL_TUMOR'

30 genes related to 'RESIDUAL_TUMOR'.

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

RESIDUAL_TUMOR Labels N
  R0 330
  R1 17
  R2 17
  RX 22
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RESIDUAL_TUMOR'

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

kruskal_wallis_P Q
SAMD1|90378 5.897e-14 8.06e-10
EEF1A1P9|441032 1.248e-13 8.06e-10
RPPH1|85495 1.757e-13 8.06e-10
PDDC1|347862 1.952e-13 8.06e-10
ZBTB3|79842 2.385e-13 8.06e-10
DOHH|83475 2.586e-13 8.06e-10
PABPN1|8106 3.834e-13 9.28e-10
ZBTB7A|51341 3.972e-13 9.28e-10
HDGFRP2|84717 5.612e-13 1.1e-09
MAP3K10|4294 5.886e-13 1.1e-09
Clinical variable #11: 'NUMBER_OF_LYMPH_NODES'

30 genes related to 'NUMBER_OF_LYMPH_NODES'.

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

NUMBER_OF_LYMPH_NODES Mean (SD) 5.73 (8.6)
  Significant markers N = 30
  pos. correlated 28
  neg. correlated 2
List of top 10 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

Table S22.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER_OF_LYMPH_NODES' by Spearman correlation test

SpearmanCorr corrP Q
HDC|3067 0.2372 5.059e-06 0.0564
OSBPL9|114883 0.2292 9.168e-06 0.0564
CNGB3|54714 0.2561 1.243e-05 0.0564
SIGLEC6|946 0.2295 1.261e-05 0.0564
COL4A4|1286 0.2218 1.809e-05 0.0564
ABCA6|23460 0.2203 2.057e-05 0.0564
DYNC2H1|79659 0.22 2.111e-05 0.0564
PELI2|57161 0.2184 2.438e-05 0.057
CPA3|1359 0.2155 3.143e-05 0.0633
L3MBTL3|84456 0.2135 3.738e-05 0.0633
Clinical variable #12: 'RACE'

30 genes related to 'RACE'.

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

RACE Labels N
  ASIAN 87
  BLACK OR AFRICAN AMERICAN 12
  NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 1
  WHITE 260
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S24.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
UTS2|10911 1.041e-17 1.95e-13
SIRPB2|284759 7.058e-11 5.19e-07
LOC162632|162632 8.335e-11 5.19e-07
POM121L10P|646074 3.927e-10 1.84e-06
LOC441294|441294 9.778e-10 3.66e-06
C14ORF181|400223 1.168e-08 3.28e-05
MGMT|4255 1.229e-08 3.28e-05
CTAGE4|100128553 1.48e-08 3.46e-05
CTAGE9|643854 1.779e-08 3.7e-05
PEX6|5190 2.75e-08 5.14e-05
Clinical variable #13: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S25.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 5
  NOT HISPANIC OR LATINO 302
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 415

  • Number of genes = 18694

  • 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, 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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