Correlation between mRNAseq expression and clinical features
Ovarian Serous Cystadenocarcinoma (Primary solid tumor)
21 April 2013  |  analyses__2013_04_21
Maintainer Information
Citation Information
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Ovarian Serous Cystadenocarcinoma (Primary solid tumor cohort) - 21 April 2013: Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1BZ640R
Overview
Introduction

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

Summary

Testing the association between 18555 genes and 4 clinical features across 261 samples, statistically thresholded by Q value < 0.05, 3 clinical features related to at least one genes.

  • 1 gene correlated to 'Time to Death'.

    • KRTCAP3|200634

  • 57 genes correlated to 'AGE'.

    • STS|412 ,  LRP6|4040 ,  C8ORF55|51337 ,  EIF4E3|317649 ,  C12ORF4|57102 ,  ...

  • 1 gene correlated to 'TUMOR.STAGE'.

    • BACE1|23621

  • No genes correlated to 'KARNOFSKY.PERFORMANCE.SCORE'

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=1 shorter survival N=0 longer survival N=1
AGE Spearman correlation test N=57 older N=30 younger N=27
KARNOFSKY PERFORMANCE SCORE Spearman correlation test   N=0        
TUMOR STAGE Spearman correlation test N=1 higher stage N=1 lower stage N=0
Clinical variable #1: 'Time to Death'

One gene related to 'Time to Death'.

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

Time to Death Duration (Months) 0.3-180.2 (median=28.2)
  censored N = 112
  death N = 147
     
  Significant markers N = 1
  associated with shorter survival 0
  associated with longer survival 1
List of one gene significantly associated with 'Time to Death' by Cox regression test

Table S2.  Get Full Table List of one gene significantly associated with 'Time to Death' by Cox regression test

HazardRatio Wald_P Q C_index
KRTCAP3|200634 0.68 2.147e-06 0.04 0.403

Figure S1.  Get High-res Image As an example, this figure shows the association of KRTCAP3|200634 to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 2.15e-06 with univariate Cox regression analysis using continuous log-2 expression values.

Clinical variable #2: 'AGE'

57 genes related to 'AGE'.

Table S3.  Basic characteristics of clinical feature: 'AGE'

AGE Mean (SD) 58.95 (11)
  Significant markers N = 57
  pos. correlated 30
  neg. correlated 27
List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

Table S4.  Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
STS|412 -0.3941 7.256e-11 1.35e-06
LRP6|4040 0.3679 1.469e-09 2.72e-05
C8ORF55|51337 -0.3595 3.661e-09 6.79e-05
EIF4E3|317649 -0.3556 5.503e-09 0.000102
C12ORF4|57102 0.3554 5.62e-09 0.000104
APPL2|55198 0.3475 1.28e-08 0.000237
PDHA1|5160 -0.3457 1.528e-08 0.000283
GREB1|9687 -0.3447 1.698e-08 0.000315
CLSTN3|9746 0.3436 1.892e-08 0.000351
ADAM15|8751 -0.3408 2.507e-08 0.000465

Figure S2.  Get High-res Image As an example, this figure shows the association of STS|412 to 'AGE'. P value = 7.26e-11 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'KARNOFSKY.PERFORMANCE.SCORE'

No gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S5.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 74.29 (12)
  Score N
  60 5
  80 8
  100 1
     
  Significant markers N = 0
Clinical variable #4: 'TUMOR.STAGE'

One gene related to 'TUMOR.STAGE'.

Table S6.  Basic characteristics of clinical feature: 'TUMOR.STAGE'

TUMOR.STAGE Mean (SD) 3.06 (0.44)
  N
  Stage 2 18
  Stage 3 209
  Stage 4 33
     
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene significantly correlated to 'TUMOR.STAGE' by Spearman correlation test

Table S7.  Get Full Table List of one gene significantly correlated to 'TUMOR.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
BACE1|23621 0.2989 9.136e-07 0.017

Figure S3.  Get High-res Image As an example, this figure shows the association of BACE1|23621 to 'TUMOR.STAGE'. P value = 9.14e-07 with Spearman correlation analysis.

Methods & Data
Input
  • Expresson data file = OV-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt

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

  • Number of patients = 261

  • Number of genes = 18555

  • Number of clinical features = 4

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

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] 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)