Correlation between mRNAseq expression and clinical features
Head and Neck Squamous Cell Carcinoma (Primary solid tumor)
23 May 2013  |  analyses__2013_05_23
Maintainer Information
Citation Information
doi:10.7908/C1513W70
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1513W70
Overview
Introduction

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

Summary

Testing the association between 18388 genes and 9 clinical features across 302 samples, statistically thresholded by Q value < 0.05, 6 clinical features related to at least one genes.

  • 11 genes correlated to 'Time to Death'.

    • CYB5B|80777 ,  FGD3|89846 ,  TOMM34|10953 ,  LOC728989|728989 ,  FRMD5|84978 ,  ...

  • 36 genes correlated to 'GENDER'.

    • XIST|7503 ,  ZFY|7544 ,  PRKY|5616 ,  RPS4Y1|6192 ,  DDX3Y|8653 ,  ...

  • 6 genes correlated to 'NUMBERPACKYEARSSMOKED'.

    • GLI2|2736 ,  TMTC3|160418 ,  B4GALNT3|283358 ,  DPH3|285381 ,  MCOLN1|57192 ,  ...

  • 2 genes correlated to 'LYMPH.NODE.METASTASIS'.

    • EPS8L2|64787 ,  TRIM16|10626

  • 67 genes correlated to 'NUMBER.OF.LYMPH.NODES'.

    • ARL4C|10123 ,  TGM1|7051 ,  SPOCK1|6695 ,  MPZL2|10205 ,  GDPD3|79153 ,  ...

  • 1 gene correlated to 'NEOPLASM.DISEASESTAGE'.

    • FRS2|10818

  • No genes correlated to 'AGE', 'RADIATIONS.RADIATION.REGIMENINDICATION', and 'YEAROFTOBACCOSMOKINGONSET'.

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=11 shorter survival N=4 longer survival N=7
AGE Spearman correlation test   N=0        
GENDER t test N=36 male N=14 female N=22
RADIATIONS RADIATION REGIMENINDICATION t test   N=0        
NUMBERPACKYEARSSMOKED Spearman correlation test N=6 higher numberpackyearssmoked N=4 lower numberpackyearssmoked N=2
YEAROFTOBACCOSMOKINGONSET Spearman correlation test   N=0        
LYMPH NODE METASTASIS ANOVA test N=2        
NUMBER OF LYMPH NODES Spearman correlation test N=67 higher number.of.lymph.nodes N=22 lower number.of.lymph.nodes N=45
NEOPLASM DISEASESTAGE ANOVA test N=1        
Clinical variable #1: 'Time to Death'

11 genes related to 'Time to Death'.

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

Time to Death Duration (Months) 0.1-210.9 (median=14.8)
  censored N = 179
  death N = 120
     
  Significant markers N = 11
  associated with shorter survival 4
  associated with longer survival 7
List of top 10 genes significantly associated with 'Time to Death' by Cox regression test

Table S2.  Get Full Table List of top 10 genes significantly associated with 'Time to Death' by Cox regression test

HazardRatio Wald_P Q C_index
CYB5B|80777 2.5 2.522e-08 0.00046 0.63
FGD3|89846 0.63 7.202e-08 0.0013 0.335
TOMM34|10953 2.3 1.373e-07 0.0025 0.647
LOC728989|728989 0.64 3.751e-07 0.0069 0.331
FRMD5|84978 1.27 7.547e-07 0.014 0.658
TP53INP1|94241 0.64 7.624e-07 0.014 0.357
ZNF266|10781 0.45 1.227e-06 0.023 0.362
SLC35E2|728661 0.57 1.769e-06 0.033 0.381
SLC25A45|283130 0.59 1.933e-06 0.036 0.362
POLR2C|5432 2.6 2.355e-06 0.043 0.613

Figure S1.  Get High-res Image As an example, this figure shows the association of CYB5B|80777 to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 2.52e-08 with univariate Cox regression analysis using continuous log-2 expression values.

Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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

AGE Mean (SD) 61.05 (12)
  Significant markers N = 0
Clinical variable #3: 'GENDER'

36 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 81
  MALE 221
     
  Significant markers N = 36
  Higher in MALE 14
  Higher in FEMALE 22
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
XIST|7503 -46.26 2.87e-115 5.28e-111 0.9985
ZFY|7544 42.16 4.214e-96 7.75e-92 0.9957
PRKY|5616 28.23 2.038e-64 3.75e-60 0.9946
RPS4Y1|6192 36.84 1.284e-57 2.36e-53 0.9997
DDX3Y|8653 36.45 1.494e-50 2.75e-46 0.9958
USP9Y|8287 32.22 2.389e-43 4.39e-39 0.9982
TSIX|9383 -18.22 3.823e-39 7.03e-35 0.9761
UTY|7404 28.95 5.546e-36 1.02e-31 0.9933
KDM5D|8284 30.36 1.94e-35 3.56e-31 0.997
NLGN4Y|22829 21.67 1.267e-27 2.33e-23 0.9887

Figure S2.  Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 2.87e-115 with T-test analysis.

Clinical variable #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S6.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 78
  YES 224
     
  Significant markers N = 0
Clinical variable #5: 'NUMBERPACKYEARSSMOKED'

6 genes related to 'NUMBERPACKYEARSSMOKED'.

Table S7.  Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED Mean (SD) 49.8 (37)
  Significant markers N = 6
  pos. correlated 4
  neg. correlated 2
List of 6 genes significantly correlated to 'NUMBERPACKYEARSSMOKED' by Spearman correlation test

Table S8.  Get Full Table List of 6 genes significantly correlated to 'NUMBERPACKYEARSSMOKED' by Spearman correlation test

SpearmanCorr corrP Q
GLI2|2736 0.3738 6.517e-07 0.012
TMTC3|160418 0.3711 7.902e-07 0.0145
B4GALNT3|283358 0.3606 1.692e-06 0.0311
DPH3|285381 -0.3602 1.748e-06 0.0321
MCOLN1|57192 -0.3574 2.116e-06 0.0389
KCNQ5|56479 0.3557 2.388e-06 0.0439

Figure S3.  Get High-res Image As an example, this figure shows the association of GLI2|2736 to 'NUMBERPACKYEARSSMOKED'. P value = 6.52e-07 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #6: 'YEAROFTOBACCOSMOKINGONSET'

No gene related to 'YEAROFTOBACCOSMOKINGONSET'.

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

YEAROFTOBACCOSMOKINGONSET Mean (SD) 1964.56 (12)
  Significant markers N = 0
Clinical variable #7: 'LYMPH.NODE.METASTASIS'

2 genes related to 'LYMPH.NODE.METASTASIS'.

Table S10.  Basic characteristics of clinical feature: 'LYMPH.NODE.METASTASIS'

LYMPH.NODE.METASTASIS Labels N
  N0 99
  N1 33
  N2 6
  N2A 4
  N2B 55
  N2C 32
  N3 5
  NX 60
     
  Significant markers N = 2
List of 2 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

Table S11.  Get Full Table List of 2 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

ANOVA_P Q
EPS8L2|64787 1.729e-06 0.0318
TRIM16|10626 1.994e-06 0.0367

Figure S4.  Get High-res Image As an example, this figure shows the association of EPS8L2|64787 to 'LYMPH.NODE.METASTASIS'. P value = 1.73e-06 with ANOVA analysis.

Clinical variable #8: 'NUMBER.OF.LYMPH.NODES'

67 genes related to 'NUMBER.OF.LYMPH.NODES'.

Table S12.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.68 (5.3)
  Significant markers N = 67
  pos. correlated 22
  neg. correlated 45
List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

Table S13.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
ARL4C|10123 0.3894 1.129e-09 2.08e-05
TGM1|7051 -0.377 4.13e-09 7.59e-05
SPOCK1|6695 0.3751 4.982e-09 9.16e-05
MPZL2|10205 -0.3628 1.691e-08 0.000311
GDPD3|79153 -0.3526 4.445e-08 0.000817
PCGF2|7703 0.3509 5.229e-08 0.000961
ABLIM1|3983 -0.3502 5.59e-08 0.00103
SPRR2F|6705 -0.3492 7.509e-08 0.00138
C1ORF216|127703 0.3464 7.901e-08 0.00145
SLC13A4|26266 -0.3466 8.279e-08 0.00152

Figure S5.  Get High-res Image As an example, this figure shows the association of ARL4C|10123 to 'NUMBER.OF.LYMPH.NODES'. P value = 1.13e-09 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #9: 'NEOPLASM.DISEASESTAGE'

One gene related to 'NEOPLASM.DISEASESTAGE'.

Table S14.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 16
  STAGE II 47
  STAGE III 41
  STAGE IVA 147
  STAGE IVB 6
     
  Significant markers N = 1
List of one gene differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S15.  Get Full Table List of one gene differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
FRS2|10818 8.906e-08 0.00164

Figure S6.  Get High-res Image As an example, this figure shows the association of FRS2|10818 to 'NEOPLASM.DISEASESTAGE'. P value = 8.91e-08 with ANOVA analysis.

Methods & Data
Input

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

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

  • Number of patients = 302

  • Number of genes = 18388

  • 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

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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