Correlation between mRNAseq expression and clinical features
Stomach Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C1QR4VZK
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1QR4VZK
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.

  • 23 genes correlated to 'AGE'.

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

  • 28 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • FMO2|2327_CALCULATED ,  LOC641298|641298|1OF2_CALCULATED ,  UVSSA|57654_CALCULATED ,  METAZOA_SRP|?|35OF109_CALCULATED ,  GNB4|59345_CALCULATED ,  ...

  • 740 genes correlated to 'PATHOLOGY.T.STAGE'.

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

  • 6 genes correlated to 'PATHOLOGY.N.STAGE'.

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

  • 2 genes correlated to 'GENDER'.

    • LOC389906|389906_CALCULATED ,  AY927613|?_CALCULATED

  • 384 genes correlated to 'HISTOLOGICAL.TYPE'.

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

  • 696 genes correlated to 'COMPLETENESS.OF.RESECTION'.

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

  • 3 genes correlated to 'NUMBER.OF.LYMPH.NODES'.

    • SIGLEC6|946_CALCULATED ,  ABCA6|23460_CALCULATED ,  BX538254|?_CALCULATED

  • 298 genes correlated to 'RACE'.

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

  • No genes correlated to 'Time to Death', '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
Time to Death Cox regression test   N=0        
AGE Spearman correlation test N=23 older N=16 younger N=7
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=28        
PATHOLOGY T STAGE Spearman correlation test N=740 higher stage N=735 lower stage N=5
PATHOLOGY N STAGE Spearman correlation test N=6 higher stage N=6 lower stage N=0
PATHOLOGY M STAGE Kruskal-Wallis test   N=0        
GENDER Wilcoxon test N=2 male N=2 female N=0
HISTOLOGICAL TYPE Kruskal-Wallis test N=384        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test   N=0        
COMPLETENESS OF RESECTION Kruskal-Wallis test N=696        
NUMBER OF LYMPH NODES Spearman correlation test N=3 higher number.of.lymph.nodes N=3 lower number.of.lymph.nodes N=0
RACE Kruskal-Wallis test N=298        
Clinical variable #1: 'Time to Death'

No gene related to 'Time to Death'.

Table S1.  Basic characteristics of clinical feature: 'Time to Death'

Time to Death Duration (Months) 0.1-105.1 (median=12)
  censored N = 176
  death N = 67
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

23 genes related to 'AGE'.

Table S2.  Basic characteristics of clinical feature: 'AGE'

AGE Mean (SD) 65.75 (11)
  Significant markers N = 23
  pos. correlated 16
  neg. correlated 7
List of top 10 genes differentially expressed by 'AGE'

Table S3.  Get Full Table List of top 10 genes significantly correlated to 'AGE' 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 0.0144
TMEM240|339453_CALCULATED -0.2972 7.558e-07 0.0177
PEX7|5191_CALCULATED 0.2938 1.03e-06 0.0241
TMEM132C|92293_CALCULATED -0.3038 1.46e-06 0.0341
KIAA0845|?_CALCULATED -0.2844 2.314e-06 0.054
CSF2|1437_CALCULATED 0.2909 2.411e-06 0.0563
SPTBN4|57731_CALCULATED -0.276 4.712e-06 0.11
ACAT2|39_CALCULATED 0.2743 5.387e-06 0.126
SNORD35A|26816_CALCULATED 0.2728 6.367e-06 0.149
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

28 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 43
  STAGE III 3
  STAGE IIIA 40
  STAGE IIIB 32
  STAGE IIIC 23
  STAGE IV 27
     
  Significant markers N = 28
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Clinical variable #4: 'PATHOLOGY.T.STAGE'

740 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
  1 13
  2 70
  3 107
  4 75
     
  Significant markers N = 740
  pos. correlated 735
  neg. correlated 5
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 3.71e-07
SNTB2|6645_CALCULATED 0.3862 7.404e-11 1.73e-06
PLN|5350_CALCULATED 0.3834 1.047e-10 2.45e-06
KCNE4|23704_CALCULATED 0.3822 1.2e-10 2.8e-06
PPP1R12A|4659_CALCULATED 0.3794 1.677e-10 3.92e-06
RYR2|6262_CALCULATED 0.3781 1.974e-10 4.61e-06
AF268386|?_CALCULATED 0.3743 3.093e-10 7.22e-06
NPTX1|4884_CALCULATED 0.3739 3.495e-10 8.16e-06
CALD1|800_CALCULATED 0.3723 3.894e-10 9.1e-06
Clinical variable #5: 'PATHOLOGY.N.STAGE'

6 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
  0 91
  1 76
  2 46
  3 49
     
  Significant markers N = 6
  pos. correlated 6
  neg. correlated 0
List of 6 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S9.  Get Full Table List of 6 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
ABCA6|23460_CALCULATED 0.2893 1.913e-06 0.0447
BX538254|?_CALCULATED 0.2821 3.516e-06 0.0821
DYNC2H1|79659_CALCULATED 0.2743 6.608e-06 0.154
C1ORF150|148823_CALCULATED 0.276 8.054e-06 0.188
SIGLEC6|946_CALCULATED 0.2712 8.47e-06 0.198
ITPR1|3708_CALCULATED 0.271 8.636e-06 0.202
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
  M0 243
  M1 18
  MX 13
     
  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 105
  MALE 169
     
  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'. 33 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
LOC389906|389906_CALCULATED 5855.5 2.242e-06 0.0523 0.67
AY927613|?_CALCULATED 5873 2.565e-06 0.0599 0.669
Clinical variable #8: 'HISTOLOGICAL.TYPE'

384 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 PAPILLARY TYPE 1
  STOMACH INTESTINAL ADENOCARCINOMA  MUCINOUS TYPE 14
  STOMACH INTESTINAL ADENOCARCINOMA  PAPILLARY TYPE 4
  STOMACH ADENOCARCINOMA SIGNET RING TYPE 1
     
  Significant markers N = 384
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

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 7
  YES 267
     
  Significant markers N = 0
Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

696 genes related to 'COMPLETENESS.OF.RESECTION'.

Table S16.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 216
  R1 9
  R2 10
  RX 22
     
  Significant markers N = 696
List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

3 genes related to 'NUMBER.OF.LYMPH.NODES'.

Table S18.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 4.86 (7.1)
  Significant markers N = 3
  pos. correlated 3
  neg. correlated 0
List of 3 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S19.  Get Full Table List of 3 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
SIGLEC6|946_CALCULATED 0.2853 8.101e-06 0.189
ABCA6|23460_CALCULATED 0.2847 8.531e-06 0.199
BX538254|?_CALCULATED 0.2841 8.884e-06 0.208
Clinical variable #12: 'RACE'

298 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 = 298
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

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

ANOVA analysis

For multi-class clinical features (ordinal or nominal), one-way analysis of variance (Howell 2002) was applied to compare the log2-expression levels between different clinical classes using 'anova' function in R

Student's t-test analysis

For two-class clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the log2-expression levels between the two clinical classes using 't.test' function in R

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] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[4] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[5] 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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