Correlation between RPPA expression and clinical features
Head and Neck Squamous Cell Carcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1WS8S4D
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/C1WS8S4D
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 11 clinical features across 212 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 7 clinical features related to at least one genes.

  • 4 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • ARID1A|ARID1A-M-V ,  RPS6|S6_PS240_S244-R-V ,  MAPK1 MAPK3|MAPK_PT202_Y204-R-V ,  CHGA|CHROMOGRANIN-A-N-TERM-R-E

  • 9 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 ,  ...

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

    • SRC|SRC_PY416-R-C ,  ANXA1|ANNEXIN_I-R-V ,  YAP1|YAP_PS127-R-C ,  MAPK9|JNK2-R-C ,  PRKCA |PKC-ALPHA_PS657-R-V ,  ...

  • 6 genes correlated to 'GENDER'.

    • YAP1|YAP_PS127-R-C ,  MAPK14|P38_PT180_Y182-R-V ,  MAPK1 MAPK3|MAPK_PT202_Y204-R-V ,  RPS6|S6_PS235_S236-R-V ,  BAD|BAD_PS112-R-V ,  ...

  • 2 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • BCL2|BCL-2-M-V ,  COL6A1|COLLAGEN_VI-R-V

  • 2 genes correlated to 'NUMBERPACKYEARSSMOKED'.

    • TP63|P63-R-E ,  CHEK2|CHK2-M-C

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

    • ANXA1|ANNEXIN_I-R-V ,  SRC|SRC_PY416-R-C ,  YAP1|YAP_PS127-R-C ,  PRKCA |PKC-ALPHA_PS657-R-V ,  FN1|FIBRONECTIN-R-C ,  ...

  • No genes correlated to 'Time to Death', 'AGE', 'RACE', and 'ETHNICITY'.

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=0        
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=4        
PATHOLOGY T STAGE Spearman correlation test N=9 higher stage N=3 lower stage N=6
PATHOLOGY N STAGE Spearman correlation test N=8 higher stage N=3 lower stage N=5
GENDER Wilcoxon test N=6 male N=6 female N=0
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test N=2 yes N=2 no N=0
NUMBERPACKYEARSSMOKED Spearman correlation test N=2 higher numberpackyearssmoked N=2 lower numberpackyearssmoked N=0
NUMBER OF LYMPH NODES Spearman correlation test N=8 higher number.of.lymph.nodes N=4 lower number.of.lymph.nodes N=4
RACE Kruskal-Wallis test   N=0        
ETHNICITY Wilcoxon 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 (Years) 45-3837 (median=1207)
  censored N = 92
  death N = 77
     
  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'

4 genes 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 = 4
List of 4 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S4.  Get Full Table List of 4 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
ARID1A|ARID1A-M-V 5.173e-06 0.000828
RPS6|S6_PS240_S244-R-V 0.0006838 0.109
MAPK1 MAPK3|MAPK_PT202_Y204-R-V 0.0009772 0.154
CHGA|CHROMOGRANIN-A-N-TERM-R-E 0.001507 0.237
Clinical variable #4: 'PATHOLOGY.T.STAGE'

9 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 = 9
  pos. correlated 3
  neg. correlated 6
List of 9 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S6.  Get Full Table List of 9 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
MAPK14|P38_PT180_Y182-R-V -0.2475 0.0003584 0.0555
SRC|SRC_PY527-R-V -0.2423 0.0004812 0.0741
CCNB1|CYCLIN_B1-R-V 0.239 0.0005756 0.0881
CDC2|CDK1-R-V 0.2294 0.0009677 0.147
Clinical variable #5: 'PATHOLOGY.N.STAGE'

8 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 = 8
  pos. correlated 3
  neg. correlated 5
List of 8 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S8.  Get Full Table List of 8 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
MAPK9|JNK2-R-C 0.2675 0.0003315 0.052
PRKCA |PKC-ALPHA_PS657-R-V 0.2574 0.0005621 0.0877
SRC|SRC_PY527-R-V -0.2556 0.0006167 0.0956
SYP|SYNAPTOPHYSIN-R-E 0.2532 0.0006964 0.107
ERBB2|HER2_PY1248-R-V -0.2498 0.0008275 0.127
Clinical variable #6: 'GENDER'

6 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 62
  MALE 150
     
  Significant markers N = 6
  Higher in MALE 6
  Higher in FEMALE 0
List of 6 genes differentially expressed by 'GENDER'

Table S10.  Get Full Table List of 6 genes differentially expressed by 'GENDER'. 0 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
YAP1|YAP_PS127-R-C 2903 1.719e-05 0.00275 0.6878
MAPK14|P38_PT180_Y182-R-V 3126 0.000177 0.0281 0.6639
MAPK1 MAPK3|MAPK_PT202_Y204-R-V 3207 0.0003847 0.0608 0.6552
RPS6|S6_PS235_S236-R-V 3284 0.000777 0.122 0.6469
BAD|BAD_PS112-R-V 3289 0.0008123 0.127 0.6463
SRC|SRC_PY527-R-V 3354 0.00143 0.222 0.6394
Clinical variable #7: 'RADIATIONS.RADIATION.REGIMENINDICATION'

2 genes 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 = 2
  Higher in YES 2
  Higher in NO 0
List of 2 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S12.  Get Full Table List of 2 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

W(pos if higher in 'YES') wilcoxontestP Q AUC
BCL2|BCL-2-M-V 2759 4.985e-06 0.000798 0.7005
COL6A1|COLLAGEN_VI-R-V 3254 0.0008342 0.133 0.6467
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 differentially expressed by 'NUMBERPACKYEARSSMOKED'

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
Clinical variable #9: 'NUMBER.OF.LYMPH.NODES'

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

Table S15.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.86 (5.1)
  Significant markers N = 8
  pos. correlated 4
  neg. correlated 4
List of 8 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S16.  Get Full Table List of 8 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
YAP1|YAP_PS127-R-C -0.2676 0.0004187 0.0662
PRKCA |PKC-ALPHA_PS657-R-V 0.2594 0.0006366 0.0999
FN1|FIBRONECTIN-R-C 0.2556 0.0007665 0.12
SYP|SYNAPTOPHYSIN-R-E 0.2553 0.0007787 0.121
AXL|AXL-M-C 0.2481 0.001105 0.17
SRC|SRC_PY527-R-V -0.2371 0.001848 0.283
Clinical variable #10: 'RACE'

No gene related to 'RACE'.

Table S17.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 3
  BLACK OR AFRICAN AMERICAN 19
  WHITE 182
     
  Significant markers N = 0
Clinical variable #11: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S18.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 13
  NOT HISPANIC OR LATINO 190
     
  Significant markers N = 0
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 = 11

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)
Copyright © 2015 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle