Correlation between mRNAseq expression and clinical features
Stomach Adenocarcinoma (Primary solid tumor)
21 April 2013  |  analyses__2013_04_21
Maintainer Information
Citation Information
doi:10.7908/C13R0QVG
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Stomach Adenocarcinoma (Primary solid tumor cohort) - 21 April 2013: Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C13R0QVG
Overview
Introduction

This pipeline uses various statistical tests to identify mRNAs whose expression levels correlated to selected clinical features.

Summary

Testing the association between 23411 genes and 11 clinical features across 147 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.

  • 2 genes correlated to 'AGE'.

    • ADIPOQ|9370_CALCULATED ,  KIAA0845|?_CALCULATED

  • 17 genes correlated to 'GENDER'.

    • TSIX|9383_CALCULATED ,  XIST|7503_CALCULATED ,  DDX3Y|8653_CALCULATED ,  ZFY|7544_CALCULATED ,  PRKY|5616_CALCULATED ,  ...

  • 78 genes correlated to 'HISTOLOGICAL.TYPE'.

    • RPS27|6232_CALCULATED ,  HOOK3|84376_CALCULATED ,  MDFIC|29969_CALCULATED ,  RPUSD3|285367_CALCULATED ,  ARSB|411_CALCULATED ,  ...

  • 43 genes correlated to 'PATHOLOGY.T'.

    • PLN|5350_CALCULATED ,  JAKMIP2|9832_CALCULATED ,  CALD1|800_CALCULATED ,  NEXN|91624_CALCULATED ,  KCNMA1|3778_CALCULATED ,  ...

  • 1 gene correlated to 'TUMOR.STAGE'.

    • SCG2|7857_CALCULATED

  • 34 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • LOC84931|84931_CALCULATED ,  RPAIN|84268_CALCULATED ,  S100A4|6275_CALCULATED ,  MFSD7|84179_CALCULATED ,  MIR3916|100500849_CALCULATED ,  ...

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

    • ZNF865|100507290_CALCULATED ,  C19ORF68|374920_CALCULATED ,  GLTSCR1|29998_CALCULATED ,  LEMD2|221496_CALCULATED ,  MIR1281|100302237_CALCULATED ,  ...

  • No genes correlated to 'Time to Death', 'PATHOLOGY.N', 'PATHOLOGICSPREAD(M)', and 'NUMBER.OF.LYMPH.NODES'.

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 Q value < 0.05.

Clinical feature Statistical test Significant genes Associated with                 Associated with
Time to Death Cox regression test   N=0        
AGE Spearman correlation test N=2 older N=0 younger N=2
GENDER t test N=17 male N=10 female N=7
HISTOLOGICAL TYPE ANOVA test N=78        
PATHOLOGY T Spearman correlation test N=43 higher pT N=43 lower pT N=0
PATHOLOGY N Spearman correlation test   N=0        
PATHOLOGICSPREAD(M) ANOVA test   N=0        
TUMOR STAGE Spearman correlation test N=1 higher stage N=1 lower stage N=0
RADIATIONS RADIATION REGIMENINDICATION t test N=34 yes N=26 no N=8
COMPLETENESS OF RESECTION ANOVA test N=875        
NUMBER OF LYMPH NODES Spearman correlation test   N=0        
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) 0.1-72.2 (median=1.4)
  censored N = 98
  death N = 15
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

2 genes related to 'AGE'.

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

AGE Mean (SD) 67.24 (11)
  Significant markers N = 2
  pos. correlated 0
  neg. correlated 2
List of 2 genes significantly correlated to 'AGE' by Spearman correlation test

Table S3.  Get Full Table List of 2 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
ADIPOQ|9370_CALCULATED -0.4759 1.862e-06 0.0436
KIAA0845|?_CALCULATED -0.3889 2.042e-06 0.0478

Figure S1.  Get High-res Image As an example, this figure shows the association of ADIPOQ|9370_CALCULATED to 'AGE'. P value = 1.86e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'GENDER'

17 genes related to 'GENDER'.

Table S4.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 53
  MALE 94
     
  Significant markers N = 17
  Higher in MALE 10
  Higher in FEMALE 7
List of top 10 genes differentially expressed by 'GENDER'

Table S5.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
TSIX|9383_CALCULATED -25.9 2.952e-49 6.91e-45 0.9869
XIST|7503_CALCULATED -26.78 4.206e-48 9.84e-44 0.9851
DDX3Y|8653_CALCULATED 23.04 7.21e-24 1.69e-19 0.9749
ZFY|7544_CALCULATED 20.93 6.723e-23 1.57e-18 0.9803
PRKY|5616_CALCULATED 18.64 1.795e-22 4.2e-18 0.9777
USP9Y|8287_CALCULATED 19.51 2.644e-19 6.19e-15 0.9738
KDM5D|8284_CALCULATED 18.42 3.387e-17 7.92e-13 0.9711
EIF1AY|9086_CALCULATED 15.47 4.234e-14 9.91e-10 0.9603
UTY|7404_CALCULATED 14.83 2.286e-13 5.35e-09 0.9661
NLGN4Y|22829_CALCULATED 13.83 5.607e-12 1.31e-07 0.959

Figure S2.  Get High-res Image As an example, this figure shows the association of TSIX|9383_CALCULATED to 'GENDER'. P value = 2.95e-49 with T-test analysis.

Clinical variable #4: 'HISTOLOGICAL.TYPE'

78 genes related to 'HISTOLOGICAL.TYPE'.

Table S6.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  STOMACH ADENOCARCINOMA DIFFUSE TYPE 5
  STOMACH ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 6
  STOMACH INTESTINAL ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 4
  STOMACH INTESTINAL ADENOCARCINOMA  MUCINOUS TYPE 2
  STOMACH ADENOCARCINOMA - DIFFUSE TYPE 16
  STOMACH ADENOCARCINOMA - NOT OTHERWISE SPECIFIED (NOS) 67
  STOMACH INTESTINAL ADENOCARCINOMA - MUCINOUS TYPE 6
  STOMACH INTESTINAL ADENOCARCINOMA - PAPILLARY TYPE 3
  STOMACH INTESTINAL ADENOCARCINOMA - TUBULAR TYPE 10
  STOMACH INTESTINAL ADENOCARCINOMA - TYPE NOT OTHERWISE SPECIFIED (NOS) 23
     
  Significant markers N = 78
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S7.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
RPS27|6232_CALCULATED 4.896e-18 1.15e-13
HOOK3|84376_CALCULATED 3.42e-11 8.01e-07
MDFIC|29969_CALCULATED 2.548e-09 5.96e-05
RPUSD3|285367_CALCULATED 2.713e-09 6.35e-05
ARSB|411_CALCULATED 4.254e-09 9.96e-05
AK310493|?_CALCULATED 8.135e-09 0.00019
LIX1L|128077_CALCULATED 1.525e-08 0.000357
PIP4K2A|5305_CALCULATED 1.532e-08 0.000359
MFAP5|8076_CALCULATED 2.174e-08 0.000509
DPYSL3|1809_CALCULATED 2.278e-08 0.000533

Figure S3.  Get High-res Image As an example, this figure shows the association of RPS27|6232_CALCULATED to 'HISTOLOGICAL.TYPE'. P value = 4.9e-18 with ANOVA analysis.

Clinical variable #5: 'PATHOLOGY.T'

43 genes related to 'PATHOLOGY.T'.

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY.T'

PATHOLOGY.T Mean (SD) 2.64 (0.78)
  N
  T1 6
  T2 48
  T3 50
  T4 17
     
  Significant markers N = 43
  pos. correlated 43
  neg. correlated 0
List of top 10 genes significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

Table S9.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

SpearmanCorr corrP Q
PLN|5350_CALCULATED 0.4987 5.847e-09 0.000137
JAKMIP2|9832_CALCULATED 0.4774 3.095e-08 0.000725
CALD1|800_CALCULATED 0.4671 6.607e-08 0.00155
NEXN|91624_CALCULATED 0.4591 1.179e-07 0.00276
KCNMA1|3778_CALCULATED 0.4578 1.291e-07 0.00302
AF268386|?_CALCULATED 0.4563 1.443e-07 0.00338
SYNPO2|171024_CALCULATED 0.456 1.47e-07 0.00344
HAND2|9464_CALCULATED 0.4568 1.768e-07 0.00414
NCAM2|4685_CALCULATED 0.455 1.785e-07 0.00418
KCNE4|23704_CALCULATED 0.4485 2.484e-07 0.00581

Figure S4.  Get High-res Image As an example, this figure shows the association of PLN|5350_CALCULATED to 'PATHOLOGY.T'. P value = 5.85e-09 with Spearman correlation analysis.

Clinical variable #6: 'PATHOLOGY.N'

No gene related to 'PATHOLOGY.N'.

Table S10.  Basic characteristics of clinical feature: 'PATHOLOGY.N'

PATHOLOGY.N Mean (SD) 1.06 (0.99)
  N
  N0 41
  N1 44
  N2 20
  N3 14
     
  Significant markers N = 0
Clinical variable #7: 'PATHOLOGICSPREAD(M)'

No gene related to 'PATHOLOGICSPREAD(M)'.

Table S11.  Basic characteristics of clinical feature: 'PATHOLOGICSPREAD(M)'

PATHOLOGICSPREAD(M) Labels N
  M0 109
  M1 14
  MX 7
     
  Significant markers N = 0
Clinical variable #8: 'TUMOR.STAGE'

One gene related to 'TUMOR.STAGE'.

Table S12.  Basic characteristics of clinical feature: 'TUMOR.STAGE'

TUMOR.STAGE Mean (SD) 2.52 (1)
  N
  Stage 1 23
  Stage 2 33
  Stage 3 35
  Stage 4 24
     
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene significantly correlated to 'TUMOR.STAGE' by Spearman correlation test

Table S13.  Get Full Table List of one gene significantly correlated to 'TUMOR.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
SCG2|7857_CALCULATED 0.4319 1.439e-06 0.0337

Figure S5.  Get High-res Image As an example, this figure shows the association of SCG2|7857_CALCULATED to 'TUMOR.STAGE'. P value = 1.44e-06 with Spearman correlation analysis.

Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

34 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S14.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 5
  YES 142
     
  Significant markers N = 34
  Higher in YES 26
  Higher in NO 8
List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S15.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
LOC84931|84931_CALCULATED 11.57 1.534e-16 3.31e-12 0.9632
RPAIN|84268_CALCULATED 12.71 1.021e-13 2.2e-09 0.8958
S100A4|6275_CALCULATED 8.74 3.468e-11 7.48e-07 0.8521
MFSD7|84179_CALCULATED -9.26 4.317e-11 9.3e-07 0.8254
MIR3916|100500849_CALCULATED 7.77 2.208e-10 4.76e-06 0.8268
SNORD51|26798_CALCULATED 10.63 7.248e-10 1.56e-05 0.8914
STXBP2|6813_CALCULATED -8.87 8.721e-10 1.88e-05 0.8296
UPK2|7379_CALCULATED 8.22 2.001e-09 4.31e-05 0.8647
LINC00277|283673_CALCULATED 8.94 2.228e-09 4.8e-05 0.8634
KIAA0855|?_CALCULATED 9.15 2.424e-09 5.22e-05 0.8396

Figure S6.  Get High-res Image As an example, this figure shows the association of LOC84931|84931_CALCULATED to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 1.53e-16 with T-test analysis.

Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

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

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

COMPLETENESS.OF.RESECTION Labels N
  R0 98
  R1 6
  R2 10
  RX 22
     
  Significant markers N = 875
List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S17.  Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
ZNF865|100507290_CALCULATED 8.696e-17 2.04e-12
C19ORF68|374920_CALCULATED 4.445e-16 1.04e-11
GLTSCR1|29998_CALCULATED 5.995e-16 1.4e-11
LEMD2|221496_CALCULATED 1.696e-15 3.97e-11
MIR1281|100302237_CALCULATED 4.646e-15 1.09e-10
MIR3960|100616250_CALCULATED 5.786e-15 1.35e-10
ZC3H4|23211_CALCULATED 8.567e-15 2.01e-10
ZBTB3|79842_CALCULATED 1.745e-14 4.08e-10
SRP72|6731_CALCULATED 1.927e-14 4.51e-10
RFX1|5989_CALCULATED 4.985e-14 1.17e-09

Figure S7.  Get High-res Image As an example, this figure shows the association of ZNF865|100507290_CALCULATED to 'COMPLETENESS.OF.RESECTION'. P value = 8.7e-17 with ANOVA analysis.

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

No gene related to 'NUMBER.OF.LYMPH.NODES'.

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

NUMBER.OF.LYMPH.NODES Mean (SD) 4.26 (6.1)
  Significant markers N = 0
Methods & Data
Input

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

  • Clinical data file = STAD-TP.clin.merged.picked.txt

  • Number of patients = 147

  • Number of genes = 23411

  • Number of clinical features = 11

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

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

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

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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

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