Correlation between RPPA expression and clinical features
Head and Neck Squamous Cell Carcinoma (Primary solid tumor)
16 April 2014  |  analyses__2014_04_16
Maintainer Information
Citation Information
doi:10.7908/C1K64GPP
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between RPPA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1K64GPP
Overview
Introduction

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

Summary

Testing the association between 160 genes and 10 clinical features across 212 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.

  • 1 gene correlated to 'NEOPLASM.DISEASESTAGE'.

    • ARID1A|ARID1A-M-V

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

    • ARID1A|ARID1A-M-V ,  MAPK1 MAPK3|MAPK_PT202_Y204-R-V ,  RPS6|S6_PS240_S244-R-V ,  RPS6|S6_PS235_S236-R-V ,  AKT1 AKT2 AKT3|AKT_PS473-R-V

  • 3 genes correlated to 'PATHOLOGY.N.STAGE'.

    • SRC|SRC_PY416-R-C ,  ANXA1|ANNEXIN_I-R-V ,  YAP1|YAP_PS127-R-C

  • 1 gene correlated to 'GENDER'.

    • MAPK14|P38_PT180_Y182-R-V

  • 1 gene correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • BCL2|BCL-2-M-V

  • 2 genes correlated to 'NUMBERPACKYEARSSMOKED'.

    • TP63|P63-R-E ,  CHEK2|CHK2-M-C

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

    • ANXA1|ANNEXIN_I-R-V ,  SRC|SRC_PY416-R-C

  • No genes correlated to 'Time to Death', 'AGE', 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=0        
AGE Spearman correlation test   N=0        
NEOPLASM DISEASESTAGE ANOVA test N=1        
PATHOLOGY T STAGE Spearman correlation test N=5 higher stage N=1 lower stage N=4
PATHOLOGY N STAGE Spearman correlation test N=3 higher stage N=0 lower stage N=3
GENDER t test N=1 male N=0 female N=1
RADIATIONS RADIATION REGIMENINDICATION t test N=1 yes N=0 no N=1
NUMBERPACKYEARSSMOKED Spearman correlation test N=2 higher numberpackyearssmoked N=2 lower numberpackyearssmoked N=0
YEAROFTOBACCOSMOKINGONSET Spearman correlation test   N=0        
NUMBER OF LYMPH NODES Spearman correlation test N=2 higher number.of.lymph.nodes N=0 lower number.of.lymph.nodes N=2
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) 0.1-211 (median=18.2)
  censored N = 95
  death N = 117
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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

AGE Mean (SD) 62.12 (12)
  Significant markers N = 0
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

One gene related to 'NEOPLASM.DISEASESTAGE'.

Table S3.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 9
  STAGE II 39
  STAGE III 31
  STAGE IVA 117
  STAGE IVB 4
     
  Significant markers N = 1
List of one gene differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S4.  Get Full Table List of one gene differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
ARID1A|ARID1A-M-V 1.442e-05 0.00231

Figure S1.  Get High-res Image As an example, this figure shows the association of ARID1A|ARID1A-M-V to 'NEOPLASM.DISEASESTAGE'. P value = 1.44e-05 with ANOVA analysis.

Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

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

PATHOLOGY.T.STAGE Mean (SD) 2.97 (0.97)
  N
  1 13
  2 59
  3 53
  4 79
     
  Significant markers N = 5
  pos. correlated 1
  neg. correlated 4
List of 5 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

Table S6.  Get Full Table List of 5 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
ARID1A|ARID1A-M-V 0.3335 1.095e-06 0.000175
MAPK1 MAPK3|MAPK_PT202_Y204-R-V -0.2974 1.558e-05 0.00248
RPS6|S6_PS240_S244-R-V -0.292 2.253e-05 0.00356
RPS6|S6_PS235_S236-R-V -0.2897 2.644e-05 0.00415
AKT1 AKT2 AKT3|AKT_PS473-R-V -0.2709 8.895e-05 0.0139

Figure S2.  Get High-res Image As an example, this figure shows the association of ARID1A|ARID1A-M-V to 'PATHOLOGY.T.STAGE'. P value = 1.09e-06 with Spearman correlation analysis.

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

3 genes related to 'PATHOLOGY.N.STAGE'.

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

PATHOLOGY.N.STAGE Mean (SD) 1.09 (0.97)
  N
  0 72
  1 21
  2 79
  3 4
     
  Significant markers N = 3
  pos. correlated 0
  neg. correlated 3
List of 3 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

Table S8.  Get Full Table List of 3 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
SRC|SRC_PY416-R-C -0.3268 9.593e-06 0.00153
ANXA1|ANNEXIN_I-R-V -0.2868 0.0001137 0.0181
YAP1|YAP_PS127-R-C -0.2743 0.0002296 0.0363

Figure S3.  Get High-res Image As an example, this figure shows the association of SRC|SRC_PY416-R-C to 'PATHOLOGY.N.STAGE'. P value = 9.59e-06 with Spearman correlation analysis.

Clinical variable #6: 'GENDER'

One gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 62
  MALE 150
     
  Significant markers N = 1
  Higher in MALE 0
  Higher in FEMALE 1
List of one gene differentially expressed by 'GENDER'

Table S10.  Get Full Table List of one gene differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
MAPK14|P38_PT180_Y182-R-V -3.85 0.0001978 0.0316 0.6639

Figure S4.  Get High-res Image As an example, this figure shows the association of MAPK14|P38_PT180_Y182-R-V to 'GENDER'. P value = 0.000198 with T-test analysis.

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

One gene related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

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

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 61
  YES 151
     
  Significant markers N = 1
  Higher in YES 0
  Higher in NO 1
List of one gene differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S12.  Get Full Table List of one gene differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
BCL2|BCL-2-M-V -4.54 1.714e-05 0.00274 0.7005

Figure S5.  Get High-res Image As an example, this figure shows the association of BCL2|BCL-2-M-V to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 1.71e-05 with T-test analysis.

Clinical variable #8: 'NUMBERPACKYEARSSMOKED'

2 genes related to 'NUMBERPACKYEARSSMOKED'.

Table S13.  Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED Mean (SD) 48.65 (38)
  Significant markers N = 2
  pos. correlated 2
  neg. correlated 0
List of 2 genes significantly correlated to 'NUMBERPACKYEARSSMOKED' by Spearman correlation test

Table S14.  Get Full Table List of 2 genes significantly correlated to 'NUMBERPACKYEARSSMOKED' by Spearman correlation test

SpearmanCorr corrP Q
TP63|P63-R-E 0.3768 6.318e-05 0.0101
CHEK2|CHK2-M-C 0.352 0.0002006 0.0319

Figure S6.  Get High-res Image As an example, this figure shows the association of TP63|P63-R-E to 'NUMBERPACKYEARSSMOKED'. P value = 6.32e-05 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #9: 'YEAROFTOBACCOSMOKINGONSET'

No gene related to 'YEAROFTOBACCOSMOKINGONSET'.

Table S15.  Basic characteristics of clinical feature: 'YEAROFTOBACCOSMOKINGONSET'

YEAROFTOBACCOSMOKINGONSET Mean (SD) 1964.27 (12)
  Significant markers N = 0
Clinical variable #10: 'NUMBER.OF.LYMPH.NODES'

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

Table S16.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.86 (5.1)
  Significant markers N = 2
  pos. correlated 0
  neg. correlated 2
List of 2 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

Table S17.  Get Full Table List of 2 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
ANXA1|ANNEXIN_I-R-V -0.3176 2.437e-05 0.0039
SRC|SRC_PY416-R-C -0.2914 0.0001158 0.0184

Figure S7.  Get High-res Image As an example, this figure shows the association of ANXA1|ANNEXIN_I-R-V to 'NUMBER.OF.LYMPH.NODES'. P value = 2.44e-05 with Spearman correlation analysis. The straight line presents the best linear regression.

Methods & Data
Input

  • Expresson data file = HNSC-TP.rppa.txt

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

  • Number of patients = 212

  • Number of genes = 160

  • Number of clinical features = 10

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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