Correlation between mRNAseq expression and clinical features
Rectum Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C1HM577V
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/C1HM577V
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 18107 genes and 12 clinical features across 163 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 7 clinical features related to at least one genes.

  • 3 genes correlated to 'AGE'.

    • METT10D|79066 ,  RNGTT|8732 ,  LOC100128822|100128822

  • 1 gene correlated to 'NEOPLASM.DISEASESTAGE'.

    • AP1S2|8905

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

    • SCG2|7857 ,  ZFHX4|79776 ,  PLN|5350 ,  PRELP|5549 ,  NEXN|91624 ,  ...

  • 1 gene correlated to 'PATHOLOGY.N.STAGE'.

    • SLC26A5|375611

  • 1 gene correlated to 'PATHOLOGY.M.STAGE'.

    • TMPRSS9|360200

  • 6 genes correlated to 'GENDER'.

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

  • 72 genes correlated to 'HISTOLOGICAL.TYPE'.

    • SERPINA1|5265 ,  RAB26|25837 ,  SPDEF|25803 ,  TMEM61|199964 ,  TPM1|7168 ,  ...

  • No genes correlated to 'Time to Death', 'RADIATIONS.RADIATION.REGIMENINDICATION', 'COMPLETENESS.OF.RESECTION', 'NUMBER.OF.LYMPH.NODES', and 'RACE'.

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=3 older N=1 younger N=2
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=1        
PATHOLOGY T STAGE Spearman correlation test N=36 higher stage N=31 lower stage N=5
PATHOLOGY N STAGE Spearman correlation test N=1 higher stage N=0 lower stage N=1
PATHOLOGY M STAGE Kruskal-Wallis test N=1        
GENDER Wilcoxon test N=6 male N=6 female N=0
HISTOLOGICAL TYPE Wilcoxon test N=72 rectal mucinous adenocarcinoma N=72 rectal adenocarcinoma N=0
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test   N=0        
COMPLETENESS OF RESECTION Kruskal-Wallis test   N=0        
NUMBER OF LYMPH NODES Spearman correlation test   N=0        
RACE Kruskal-Wallis 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) 0.2-129.3 (median=14)
  censored N = 130
  death N = 21
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

3 genes related to 'AGE'.

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

AGE Mean (SD) 64.91 (12)
  Significant markers N = 3
  pos. correlated 1
  neg. correlated 2
List of 3 genes differentially expressed by 'AGE'

Table S3.  Get Full Table List of 3 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
METT10D|79066 -0.3545 3.448e-06 0.0624
RNGTT|8732 -0.3322 1.473e-05 0.267
LOC100128822|100128822 0.3306 1.627e-05 0.295
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

One gene related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 30
  STAGE II 8
  STAGE IIA 38
  STAGE IIB 2
  STAGE IIC 2
  STAGE III 6
  STAGE IIIA 9
  STAGE IIIB 23
  STAGE IIIC 14
  STAGE IV 17
  STAGE IVA 9
     
  Significant markers N = 1
List of one gene differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S5.  Get Full Table List of one gene differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
AP1S2|8905 1.301e-05 0.236
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.8 (0.67)
  N
  1 9
  2 29
  3 110
  4 14
     
  Significant markers N = 36
  pos. correlated 31
  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
SCG2|7857 0.398 1.715e-07 0.00311
ZFHX4|79776 0.3721 1.368e-06 0.0248
PLN|5350 0.3671 1.664e-06 0.0301
PRELP|5549 0.3646 1.839e-06 0.0333
NEXN|91624 0.3626 2.123e-06 0.0384
SPP1|6696 0.3577 2.962e-06 0.0536
KIAA0664|23277 -0.3577 2.969e-06 0.0537
DPYSL3|1809 0.3572 3.071e-06 0.0556
CYBRD1|79901 0.3535 3.944e-06 0.0714
BRI3BP|140707 -0.3528 4.13e-06 0.0747
Clinical variable #5: 'PATHOLOGY.N.STAGE'

One gene related to 'PATHOLOGY.N.STAGE'.

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

PATHOLOGY.N.STAGE Mean (SD) 0.68 (0.79)
  N
  0 83
  1 45
  2 32
     
  Significant markers N = 1
  pos. correlated 0
  neg. correlated 1
List of one gene differentially expressed by 'PATHOLOGY.N.STAGE'

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

SpearmanCorr corrP Q
SLC26A5|375611 -0.5456 6.534e-06 0.118
Clinical variable #6: 'PATHOLOGY.M.STAGE'

One gene related to 'PATHOLOGY.M.STAGE'.

Table S10.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 124
  M1 21
  M1A 2
  MX 14
     
  Significant markers N = 1
List of one gene differentially expressed by 'PATHOLOGY.M.STAGE'

Table S11.  Get Full Table List of one gene differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
TMPRSS9|360200 1.485e-05 0.269
Clinical variable #7: 'GENDER'

6 genes related to 'GENDER'.

Table S12.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 73
  MALE 90
     
  Significant markers N = 6
  Higher in MALE 6
  Higher in FEMALE 0
List of 6 genes differentially expressed by 'GENDER'

Table S13.  Get Full Table List of 6 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
CYORF15B|84663 1763 2.321e-11 4.2e-07 0.9794
CYORF15A|246126 1663 1.121e-10 2.03e-06 0.9725
HDHD1A|8226 1474 1.522e-09 2.75e-05 0.7756
NCRNA00183|554203 1492 2.204e-09 3.99e-05 0.7729
CA5BP|340591 1923 5.529e-06 0.0999 0.7073
DDX43|55510 2986 1.653e-05 0.299 0.7223
Clinical variable #8: 'HISTOLOGICAL.TYPE'

72 genes related to 'HISTOLOGICAL.TYPE'.

Table S14.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  RECTAL ADENOCARCINOMA 144
  RECTAL MUCINOUS ADENOCARCINOMA 13
     
  Significant markers N = 72
  Higher in RECTAL MUCINOUS ADENOCARCINOMA 72
  Higher in RECTAL ADENOCARCINOMA 0
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S15.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

W(pos if higher in 'RECTAL MUCINOUS ADENOCARCINOMA') wilcoxontestP Q AUC
SERPINA1|5265 1769 1.141e-07 0.00206 0.945
RAB26|25837 1758 1.672e-07 0.00302 0.9391
SPDEF|25803 1746 2.521e-07 0.00455 0.9327
TMEM61|199964 1703 3.253e-07 0.00588 0.9291
TPM1|7168 1736 3.534e-07 0.00638 0.9274
DRP2|1821 1723 3.68e-07 0.00665 0.9268
C20ORF56|140828 1725 5.103e-07 0.00922 0.9215
TOX|9760 1725 5.103e-07 0.00922 0.9215
FAM174B|400451 1720 6.021e-07 0.0109 0.9188
GNA14|9630 1714 7.333e-07 0.0132 0.9156
Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

No gene related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S16.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 6
  YES 157
     
  Significant markers N = 0
Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

No gene related to 'COMPLETENESS.OF.RESECTION'.

Table S17.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 121
  R1 2
  R2 12
  RX 4
     
  Significant markers N = 0
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) 2.68 (5.5)
  Significant markers N = 0
Clinical variable #12: 'RACE'

No gene related to 'RACE'.

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

RACE Labels N
  ASIAN 1
  BLACK OR AFRICAN AMERICAN 3
  WHITE 81
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 163

  • Number of genes = 18107

  • 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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