Correlation between mRNAseq expression and clinical features
Esophageal Carcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C1GM861K
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/C1GM861K
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 23891 genes and 9 clinical features across 66 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 3 clinical features related to at least one genes.

  • 51 genes correlated to 'AGE'.

    • KPNA7|402569_CALCULATED ,  RIPK3|11035_CALCULATED ,  TRIM31|11074_CALCULATED ,  DQ572107|?_CALCULATED ,  MIR4497|100616454_CALCULATED ,  ...

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

    • CLCN5|1184_CALCULATED ,  MOCOS|55034_CALCULATED ,  SEC16B|89866_CALCULATED ,  ARHGEF7|8874_CALCULATED ,  YBX2|51087_CALCULATED ,  ...

  • 309 genes correlated to 'RACE'.

    • TMC5|79838_CALCULATED ,  TSPAN8|7103_CALCULATED ,  ZG16B|124220_CALCULATED ,  CDC42EP5|148170_CALCULATED ,  CDH17|1015_CALCULATED ,  ...

  • No genes correlated to 'Time to Death', 'NEOPLASM.DISEASESTAGE', 'PATHOLOGY.N.STAGE', 'PATHOLOGY.M.STAGE', 'GENDER', and 'NUMBERPACKYEARSSMOKED'.

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=51 older N=21 younger N=30
NEOPLASM DISEASESTAGE Kruskal-Wallis test   N=0        
PATHOLOGY T STAGE Spearman correlation test N=41 higher stage N=0 lower stage N=41
PATHOLOGY N STAGE Spearman correlation test   N=0        
PATHOLOGY M STAGE Kruskal-Wallis test   N=0        
GENDER Wilcoxon test   N=0        
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
RACE Wilcoxon test N=309 white N=309 asian 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) 0-33.3 (median=3.2)
  censored N = 44
  death N = 20
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

51 genes related to 'AGE'.

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

AGE Mean (SD) 62.11 (13)
  Significant markers N = 51
  pos. correlated 21
  neg. correlated 30
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
KPNA7|402569_CALCULATED 0.6208 2.685e-08 0.000641
RIPK3|11035_CALCULATED 0.6025 8.676e-08 0.00207
TRIM31|11074_CALCULATED 0.5784 3.657e-07 0.00874
DQ572107|?_CALCULATED 0.5644 7.966e-07 0.019
MIR4497|100616454_CALCULATED -0.5952 1.044e-06 0.0249
CELSR2|1952_CALCULATED -0.5543 1.372e-06 0.0328
TMC5|79838_CALCULATED 0.5528 1.488e-06 0.0355
ACY3|91703_CALCULATED 0.5516 1.583e-06 0.0378
PGC|5225_CALCULATED 0.5818 1.671e-06 0.0399
ARHGEF19|128272_CALCULATED -0.547 2.015e-06 0.0481
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

No gene related to 'NEOPLASM.DISEASESTAGE'.

Table S4.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 4
  STAGE IA 3
  STAGE IB 2
  STAGE II 1
  STAGE IIA 21
  STAGE IIB 10
  STAGE III 6
  STAGE IIIA 6
  STAGE IIIB 5
  STAGE IIIC 1
  STAGE IV 1
     
  Significant markers N = 0
Clinical variable #4: 'PATHOLOGY.T.STAGE'

41 genes related to 'PATHOLOGY.T.STAGE'.

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.48 (0.79)
  N
  1 9
  2 16
  3 34
  4 2
     
  Significant markers N = 41
  pos. correlated 0
  neg. correlated 41
List of top 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S6.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
CLCN5|1184_CALCULATED -0.5934 4.651e-07 0.0111
MOCOS|55034_CALCULATED -0.5882 6.187e-07 0.0148
SEC16B|89866_CALCULATED -0.5881 6.249e-07 0.0149
ARHGEF7|8874_CALCULATED -0.5783 1.053e-06 0.0252
YBX2|51087_CALCULATED -0.5688 1.729e-06 0.0413
MED14|9282_CALCULATED -0.5683 1.776e-06 0.0424
ANO9|338440_CALCULATED -0.5681 1.795e-06 0.0429
LOC731275|731275_CALCULATED -0.5624 2.389e-06 0.0571
XYLB|9942_CALCULATED -0.5596 2.748e-06 0.0656
ATP11A|23250_CALCULATED -0.5585 2.913e-06 0.0696
Clinical variable #5: 'PATHOLOGY.N.STAGE'

No gene related to 'PATHOLOGY.N.STAGE'.

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.57 (0.76)
  N
  0 35
  1 18
  2 7
  3 1
     
  Significant markers N = 0
Clinical variable #6: 'PATHOLOGY.M.STAGE'

No gene related to 'PATHOLOGY.M.STAGE'.

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 49
  M1A 1
  MX 7
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

No gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 10
  MALE 56
     
  Significant markers N = 0
Clinical variable #8: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

Table S10.  Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED Mean (SD) 36.85 (21)
  Significant markers N = 0
Clinical variable #9: 'RACE'

309 genes related to 'RACE'.

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

RACE Labels N
  ASIAN 27
  WHITE 36
     
  Significant markers N = 309
  Higher in WHITE 309
  Higher in ASIAN 0
List of top 10 genes differentially expressed by 'RACE'

Table S12.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

W(pos if higher in 'WHITE') wilcoxontestP Q AUC
TMC5|79838_CALCULATED 911 3.726e-09 8.9e-05 0.9372
TSPAN8|7103_CALCULATED 873 7.901e-09 0.000189 0.9327
ZG16B|124220_CALCULATED 882.5 3.784e-08 0.000903 0.9079
CDC42EP5|148170_CALCULATED 877 5.841e-08 0.00139 0.9023
CDH17|1015_CALCULATED 872.5 8.245e-08 0.00197 0.8976
RIPK3|11035_CALCULATED 872 8.595e-08 0.00205 0.8971
FAM83E|54854_CALCULATED 871 9.277e-08 0.00221 0.8961
C11ORF9|745_CALCULATED 870 1.002e-07 0.00239 0.8951
VILL|50853_CALCULATED 869.5 1.04e-07 0.00248 0.8945
HABP2|3026_CALCULATED 820 1.051e-07 0.00251 0.9011
Methods & Data
Input

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

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

  • Number of patients = 66

  • Number of genes = 23891

  • Number of clinical features = 9

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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