Correlation between mRNAseq expression and clinical features
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (Primary solid tumor)
16 April 2014  |  analyses__2014_04_16
Maintainer Information
Citation Information
doi:10.7908/C1639NBQ
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/C1639NBQ
Overview
Introduction

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

Summary

Testing the association between 18196 genes and 9 clinical features across 146 samples, statistically thresholded by Q value < 0.05, 4 clinical features related to at least one genes.

  • 2 genes correlated to 'AGE'.

    • NXNL2|158046 ,  RRAGD|58528

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

    • ART3|419

  • 22 genes correlated to 'PATHOLOGY.M.STAGE'.

    • ARF1|375 ,  ELP3|55140 ,  HOXA4|3201 ,  FERMT1|55612 ,  CBX3|11335 ,  ...

  • 1331 genes correlated to 'HISTOLOGICAL.TYPE'.

    • TP63|8626 ,  GPR87|53836 ,  DNALI1|7802 ,  CLCA2|9635 ,  HNF1A|6927 ,  ...

  • No genes correlated to 'Time to Death', 'PATHOLOGY.T.STAGE', 'RADIATIONS.RADIATION.REGIMENINDICATION', 'NUMBERPACKYEARSSMOKED', 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=1 younger N=1
PATHOLOGY T STAGE Spearman correlation test   N=0        
PATHOLOGY N STAGE t test N=1 class1 N=0 class0 N=1
PATHOLOGY M STAGE ANOVA test N=22        
HISTOLOGICAL TYPE ANOVA test N=1331        
RADIATIONS RADIATION REGIMENINDICATION t test   N=0        
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
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) 0-177 (median=12.7)
  censored N = 115
  death N = 24
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

2 genes related to 'AGE'.

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

AGE Mean (SD) 47.52 (13)
  Significant markers N = 2
  pos. correlated 1
  neg. correlated 1
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
NXNL2|158046 -0.4137 6.141e-07 0.0112
RRAGD|58528 0.379 2.589e-06 0.0471

Figure S1.  Get High-res Image As an example, this figure shows the association of NXNL2|158046 to 'AGE'. P value = 6.14e-07 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'PATHOLOGY.T.STAGE'

No gene related to 'PATHOLOGY.T.STAGE'.

Table S4.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 1.32 (0.56)
  N
  1 79
  2 29
  3 2
  4 1
     
  Significant markers N = 0
Clinical variable #4: 'PATHOLOGY.N.STAGE'

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

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Labels N
  class0 71
  class1 36
     
  Significant markers N = 1
  Higher in class1 0
  Higher in class0 1
List of one gene differentially expressed by 'PATHOLOGY.N.STAGE'

Table S6.  Get Full Table List of one gene differentially expressed by 'PATHOLOGY.N.STAGE'

T(pos if higher in 'class1') ttestP Q AUC
ART3|419 -5.06 2.703e-06 0.0492 0.7683

Figure S2.  Get High-res Image As an example, this figure shows the association of ART3|419 to 'PATHOLOGY.N.STAGE'. P value = 2.7e-06 with T-test analysis.

Clinical variable #5: 'PATHOLOGY.M.STAGE'

22 genes related to 'PATHOLOGY.M.STAGE'.

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

PATHOLOGY.M.STAGE Labels N
  M0 62
  M1 3
  MX 50
     
  Significant markers N = 22
List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S8.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
ARF1|375 3.524e-10 6.41e-06
ELP3|55140 7.643e-10 1.39e-05
HOXA4|3201 9.333e-10 1.7e-05
FERMT1|55612 2.409e-09 4.38e-05
CBX3|11335 2.653e-09 4.83e-05
PKD1L3|342372 2.241e-08 0.000408
PZP|5858 1.307e-07 0.00238
TRIM29|23650 1.367e-07 0.00249
MC4R|4160 2.665e-07 0.00485
SSR2|6746 2.776e-07 0.00505

Figure S3.  Get High-res Image As an example, this figure shows the association of ARF1|375 to 'PATHOLOGY.M.STAGE'. P value = 3.52e-10 with ANOVA analysis.

Clinical variable #6: 'HISTOLOGICAL.TYPE'

1331 genes related to 'HISTOLOGICAL.TYPE'.

Table S9.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  ADENOSQUAMOUS 1
  CERVICAL SQUAMOUS CELL CARCINOMA 122
  ENDOCERVICAL ADENOCARCINOMA OF THE USUAL TYPE 4
  ENDOCERVICAL TYPE OF ADENOCARCINOMA 15
  ENDOMETRIOID ADENOCARCINOMA OF ENDOCERVIX 1
  MUCINOUS ADENOCARCINOMA OF ENDOCERVICAL TYPE 3
     
  Significant markers N = 1331
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S10.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
TP63|8626 1.757e-36 3.2e-32
GPR87|53836 4.724e-32 8.59e-28
DNALI1|7802 4.82e-28 8.77e-24
CLCA2|9635 1.006e-26 1.83e-22
HNF1A|6927 1.248e-26 2.27e-22
LOC642587|642587 3.698e-25 6.73e-21
PKP1|5317 3.7e-25 6.73e-21
GPR109A|338442 7.438e-25 1.35e-20
CALML3|810 8.36e-25 1.52e-20
HOXD11|3237 1.239e-24 2.25e-20

Figure S4.  Get High-res Image As an example, this figure shows the association of TP63|8626 to 'HISTOLOGICAL.TYPE'. P value = 1.76e-36 with ANOVA analysis.

Clinical variable #7: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S11.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 28
  YES 118
     
  Significant markers N = 0
Clinical variable #8: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 18.83 (11)
  Significant markers N = 0
Clinical variable #9: 'NUMBER.OF.LYMPH.NODES'

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

Table S13.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 1.21 (2.8)
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 146

  • Number of genes = 18196

  • 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

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

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] 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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